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MS21600	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background . Short implants have become popular in the reconstruction of jaws , especially in cases with limited bone height . Shorter implants , those with locking tapers and plateau root shapes , tend to have longer survival times . We retrospectively investigated the cumulative survival rates of Bicon short implants ( < 8 mm ) according to patient variables over a 5-year period . Material s and Methods . This study included 111 consecutively treated patients with 371 implants supporting fixed or removable prosthetics . Data were evaluated to acquire cumulative survival rates according to gender , age , tobacco use , surgical procedure , bone quality , and restoration type . Statistics were performed using chi-square , Mann-Whitney , and Kruskal Wallis H tests . Results . The survival rate was 97.3 % with , on average , 22.8 months of follow-up . Patients older than 60 years had higher failure rate than the other age groups ( P < 0.05 ) . Placed region , age , and bone quality had adverse effects on survival rate in the < 8 mm implant group with statistically significant difference ( P < 0.05 ) . Conclusions . Approximately 23-month follow-up data indicate that short implants with locking tapers and plateau-type roots have comparable survival rates as other types of dental implants . However , due to limitations of study , these issues remain to be further investigated in future r and omized controlled clinical trials BACKGROUND Health risks associated with smoking have been exhaustively documented and include increased incidence of periodontal disease , greater risk of osteitis following oral surgery , and compromised wound healing due to hypoxia . Information related directly to dental implants , although limited , points to higher rates of implant failures among smokers than non-smokers . This paper reports on long-term clinical outcomes of osseointegrated dental implants placed in smokers and non-smokers in a longitudinal clinical study of endosseous dental implants . METHODS In 1990 , the Dental Implant Clinical Research Group ( DICRG ) of the Department of Veterans Affairs ( DVA ) launched an 8-year , r and omized , prospect i ve clinical study of more than 2,900 endosseous dental implants in more than 800 patients at 32 study centers . Confounding variables , including smoking patterns , were recorded . For this report , new follow-up data were analyzed for two groups : 1 ) current smokers and 2 ) those who never smoked combined with those who quit . Most of the variables recorded for each implant were screened on a univariate basis as possible predictors associated with implant survival/failure . Those with P values less than 0.15 and those likely to be a factor of clinical importance were placed in a logistic regression equation and analyzed for a simultaneous effect on survival . A step-wise procedure was used to eliminate those variables that showed the least significance , until only those variables with a Wald chi-square of significance in the presence of others remained . The effects of clustering within patients and of unbalanced distribution within hospitals were st and ardized to facilitate analysis of influence of demographic variables . The GEE analysis was performed with the patient as the primary cluster . RESULTS Current data do not support earlier findings that smoking contributes to early implant failure ( placement to uncovering ) . A trend of greater failures in smokers appeared between the time after uncovering and before insertion of the prosthesis . Hydroxyapatite (HA)-coated implants had significantly lower failure rates . For the entire 3-year period , overall failures were significantly higher for smokers than non-smokers . CONCLUSIONS Results suggest that increased implant failures in smokers are not the result of poor healing or osseointegration , but of exposure of peri-implant tissues to tobacco smoke . Data also suggest that detrimental effects may be reduced by : 1 ) cessation of smoking ; 2 ) the use of preoperative antibiotics ; and 3 ) the use of HA-coated implants PURPOSE To evaluate aged partially and fully edentulous patients who received dental implants and were maintained over time . Further , to determine how the partially and edentulous ageing population s ( 65 and above ) with dental implants maintain bone levels , proper oral hygiene , and perceive benefits of dental implants . MATERIAL S AND METHODS Since 1995 , patients receiving dental implants have been prospect ively entered into an Access-based computerized program ( Triton Tacking System ) . Patient demographics ( age , sex ) , bone quality , quantity , implant location , and type of surgery have been continuously entered into the data base . The data base was queried for patients receiving implants ( first stage ) between 66 and 93 years of age . Thirty-one patients were within this age group . Twenty-five patients returned to the clinic for periodontal and dental implant evaluation . The Periodontal Index was used to evaluate selected teeth in terms of probing depth , bleeding on probing , plaque accumulation , and mobility . Using NIH Image J , radiographs taken at second stage and last examination were measured for changes in interproximal bone levels . Once identified , each patient anomalously filled out an abbreviated quality of health life form . Due to small sample size , descriptive statistics were used to compare clinical findings . RESULTS Fifteen males ranging from 78 to 84 ( mean age 84 years ) years and 16 females from 66 to 93 ( mean age 83 years ) ( age range 66 - 93 ) were contacted by phone or mail and asked to return to our office for a re-examination . For this group , the first dental implants were placed in 1996 ( n = initial two implants ) and continuously recorded through 2013 ( n = last seven implants ) . Thirty-one patients received a total of 84 implants . Two patients were edentulous , and the remaining were partially edentulous . Four implants were lost . Between implant placement and 6- to 7-year interval , 13 patients with 40 implants had a cumulative survival rate of 94.6 % . Of the original group ( n = 33 ) , three were deceased , two were in nursing homes , and three could not be located . CONCLUSIONS Aged patients receiving dental implants had excellent implant survival rates , low periodontal disease index scores with minimal changes in interproximal bone levels . Results from this study indicate that patients with advanced age , in reasonably good health , have excellent implant survival rates , excellent quality of life scores , and can be maintained in good oral health BACKGROUND The placement of an implant into a fresh extraction socket has been identified as a reliable technique , allowing a reduction in the time needed for prosthetic rehabilitation . This treatment modality is widely reported in the scientific literature ; however , the long-term outcomes and the need for guided bone regeneration ( GBR ) are still topics of debate . The aim of this prospect i ve study is to evaluate the clinical and radiologic findings from the 10-year follow-up of immediately placed implants , with and without the GBR procedure . METHODS A total of 159 implants in 91 patients are included in this study ; 101 implants required a GBR procedure simultaneously with placement . All implants were used to support a single crown restoration . The clinical /radiographic measurements were repeated each year up to the 10-year follow-up . At the 10-year follow-up visit , the papilla index and the apico-coronal location of mid-buccal soft tissue positions were recorded . RESULTS The 10-year cumulative success rate was 91.8 % ( 87.9 % in the non-GBR group and 94.1 % in the GBR group ) . The clinical attachment level ( CAL ) measurements were stable throughout the study , and 82 % of the implants showed marginal bone loss ( MBL ) of 0.6 to 1.5 mm at the 10-year visit ; moreover , these two parameters did not show significant differences between the GBR and non-GBR groups . Seventy percent of the implant sites showed acceptable outcomes in terms of interproximal papilla . The facial gingival level was more apical in the non-GBR group than in the GBR group ( P < 0.05 ) . CONCLUSIONS The present prospect i ve clinical study shows that implants placed in fresh extraction sockets had a high cumulative success rate , namely 91.8 % after 10 years . No differences were detected in survival and success rate of implants whether GBR procedures were performed or not . The CAL , MBL , and marginal level of soft tissue measurements were stable throughout the 10-year evaluation OBJECTIVES The purpose of the present clinical study was to report on the clinical performance of screw-cylinder implants with special consideration of the survival rate of short implants . MATERIAL AND METHODS In this prospect i ve study with consecutive patient recruitment , Camlog screw-cylinder implants with a particle-blasted and acid-etched microstructured surface and a triple-cam tube-in-tube implant-abutment connection have been used only . Two groups of implants were evaluated : implants of 9 and 11 mm in length were considered short , those of 13 and 16 mm were considered long . Besides clinical and radiographic parameters , data of complications , patients ' subjective evaluation of treatment outcome , general medical history and smoking habits were recorded . RESULTS Three hundred and thirty-three Camlog screw-cylinder implants were inserted in 133 patients . One hundred and twenty-nine patients were available for follow-up , representing 325 implants . The median observation period was 33 months ( Q(25 % ) 26 ; Q(75 % ) 38 ) . After a maximum observation period of 55 months , the Kaplan-Meier-survival analysis revealed no significant difference between the mean survival probabilities of 98.3 % ( n=59 , patient-related ) of short implants , and of 95.7 % of long implants ( n=70 , patient-related ) ( P=0.162 ) . No significant difference was found between implant survival rates considering maxilla ( 98.7 % ) and m and ible ( 98.2 % ) . A stratified analysis of short implants revealed a significant influence of premature cover screw exposures ( P=0.02 ) and smoking ( P=0.008 ) on implant survival . These influences were not found significant for long implants . CONCLUSIONS The prognosis of short Camlog implants is comparable with that of long implants . Therefore , their clinical use instead of performance of sophisticated vertical augmentation procedures before installation of long implants might be considered as alternative treatment option . In smokers , the use of short implants should be considered cautiously , however . The risk of premature cover screw exposure should be minimized PURPOSE This 15-year prospect i ve study evaluated the success rate and preservation of the gingival margin of single implants placed in a flapless procedure loaded immediately after extraction or after a healing period . MATERIAL S AND METHODS Immediate flapless implant placement was performed in patients who fulfilled specified inclusion criteria . Implants were either immediately restored with a provisional crown or left unloaded ( received healing abutment only ) . Implant success and gingival margin levels were evaluated after implant placement and after 1 to 15 years . RESULTS A total of 305 healthy nonsmoking subjects ( 90 men , 215 women ) were treated with 430 immediate implants during a 15-year period ( December 1994 to December 2009 ) and monitored for 1 to 15 years . Two hundred seventy-five implants received an immediate provisional crown , and 155 received a healing abutment . The implant survival rate was 93.03 % ( ± 3.74 % ) . The immediate provisional helped to maintain the original gingival margin , although the implant survival rate was higher for implants that were not immediately restored ( 96.78 % ) than for the implants that were immediately restored with a provisional ( 90.9 % ) . CONCLUSIONS This 15-year prospect i ve study showed a favorable implant success rate related to the flapless immediate implant placement protocol with healing abutment placement or an immediate provisional crown to replace a single missing tooth PURPOSE The aim of this prospect i ve comparative study was to assess whether age has influence on peri-implant health in patients treated with m and ibular two-implant overdentures during a 10-year evaluation period . MATERIAL S AND METHODS A prospect i ve study was carried out with two groups of edentulous patients , viz a younger ( n = 52 ; mean age 45 years , 35 - 50 years ) and an older ( n = 53 ; mean age 68 years , 60 - 80 years ) group . In all patients , two dental implants were placed in the interforaminal region of the m and ible and after a 3-month healing period overdentures were fabricated . Clinical and radiographic parameters were evaluated immediately after completion of the prosthetic treatment , and after 1 , 5 and 10 years . Implant loss , plaque index , gingival index , bleeding index , and probing depth were assessed as clinical parameters . Peri-implant bone loss was assessed on dental radiographs made with a st and ardized long-cone technique with a direction device . RESULTS Implant survival after 10 years was 97.1 % and 93.4 % in the younger and older group , respectively . Ten-year scores of plaque , gingiva , and bleeding were between 0 and 1 for both groups ( possible scores 0 - 3 ) , and mean probing depth was 3 mm in both groups . Mean peri-implant bone loss after 10 years was 1.2 and 1.4 mm in the younger and older patients , respectively . No significant differences were observed between the groups . CONCLUSION Clinical performance of m and ibular two-implant overdentures is equally successful in younger and older patients This prospect i ve study evaluated the long Output:	This systematic review suggests that age is not a limiting factor for dental implant therapy
MS21601	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A r and omized comparison group pretest-posttest experimental design was used to quantitatively determine the effects of environmental control measures on patients with allergic rhinitis . Environmental controls included wrapping the mattress with a vinyl cover , washing the top bedding cover with 55 degrees C hot water every two weeks , removal of soft furniture , and wet cleaning of the bedroom floor every day . Thirty subjects were r and omly assigned to experimental and control groups . The amount of house dust mites in dust sample s collected from the bedroom floor , bedding and mattress , as well as the nasal symptoms of patients , were measured twice at one-month intervals . A significant decrease in house dust mites in dust sample s and relief in patients ' nasal symptoms were observed in the experimental group who had environmental controls Background : Environmental control has been put forward as an integral part of the management of house dust mite ( HDM ) allergy in sensitized patients . To vali date this statement allergic disorders involved in HDM allergy – allergic asthma , rhinitis and atopic eczema/dermatitis syndrome ( AEDS ) – should be taken together and studied in terms of the efficacy of environmental control . Because a generic quality of life question naire exceeds the border of disease , this may be used as major outcome parameter BACKGROUND Encasing bedding in impermeable covers reduces exposure to house-dust mites , but the clinical benefit of this intervention as part of mite-avoidance measures for patients with allergic rhinitis is not known . We performed a multicenter , r and omized , placebo-controlled trial of one year of use of impermeable bedding covers in the bedrooms of patients with rhinitis who were sensitized to house-dust mites to determine the effects on the signs and symptoms of disease . METHODS Three participating university medical centers enrolled 279 patients with allergic rhinitis who were r and omly assigned to receive impermeable or non-impermeable ( control ) covers for their mattress , pillow , and duvet or blanket . At the start of the study , all participants received information on general allergen-avoidance measures . The severity of rhinitis was measured on a rhinitis-specific visual-analogue scale and by means of a daily symptom score and nasal allergen provocation testing . We also measured the concentrations of Dermatophagoides pteronyssinus ( Der p1 ) and D. farinae ( Der f1 ) in dust from patients ' mattresses , bedroom floors , and living-room floors at base line and after 12 months as a measure of the efficacy of the intervention . RESULTS A total of 232 patients completed the study . There was a significant reduction in Der p1 and Der f1 concentrations in the mattresses of the impermeable-cover group , whereas there was no significant reduction in the control group . However , there was no significant effect on the clinical outcome measures . Analyses of subgroups defined according to age , level of exposure , type and severity of sensitization , or characteristics of the patient 's home had similar results . CONCLUSIONS Mite-proof bedding covers , as part of a structured allergy-control program , reduced the level of exposure to mite allergens . Despite the success of the intervention , this single avoidance measure did not lead to a significant improvement of clinical symptoms in patients with allergic rhinitis A double blind , r and omized , comparative study versus placebo , was done during 6 months in 32 children , aged 4 - 12 years , who suffer from either allergic asthma or rhinitis or both , slept in a bedroom rich in dust mite , have well documented allergy solely to house dust mite ( H.D.M. ) , and a condition severe enough to require continuous medication . After thorough cleaning , their bedrooms were sprayed on day 0 and day 90 with the total content of a canister containing either Acardust or Placebo . Rooms were cleaned regularly throughout the study period . Each child completed an individual daily score card ( scales from 0 - 3 ) for asthma , and rhinitis symptoms , medication taken , and any additional symptoms . Peak flow was recorded twice weekly . All the children were examined every month ( at the clinic ) when also PFF , FEVI , doctor 's and patient 's opinion of clinical symptoms were recorded according to the same scale ( 0 - 3 ) and dust sample s from child 's bedroom were examined for H.D.M. antigen content . At day 0 , 90 and 180 , total IgE and dust mite specific IgE determination was done . At the end of the study , patient 's and doctor 's opinion about the spray 's efficacy were recorded on a scale from 0 - 3 . The results were in favor of Acardust for asthma , according to patient 's opinion ( p = 0.001 ) , doctor 's opinion ( p = 0.04 ) and individual score cards ( p = 0.03 ) , and for nasal secretion ( p = 0.01 ) , sneezing and lacrimation ( p = 0.02 ) ; concurrent medication dropped significantly ( p = 0.01 ) in the Acardust group . No side-effects were reported . We consider Acardust a safe and valuable preventive treatment in H.D.M. allergy BACKGROUND Data for trends in prevalence of asthma , allergic rhinoconjunctivitis , and eczema over time are scarce . We repeated the International Study of Asthma and Allergies in Childhood ( ISAAC ) at least 5 years after Phase One , to examine changes in the prevalence of symptoms of these disorders . METHODS For the ISAAC Phase Three study , between 2002 and 2003 , we did a cross-sectional question naire survey of 193,404 children aged 6 - 7 years from 66 centres in 37 countries , and 304,679 children aged 13 - 14 years from 106 centres in 56 countries , chosen from a r and om sample of schools in a defined geographical area . FINDINGS Phase Three was completed a mean of 7 years after Phase One . Most centres showed a change in prevalence of 1 or more SE for at least one disorder , with increases being twice as common as decreases , and increases being more common in the 6 - 7 year age-group than in the 13 - 14 year age-group , and at most levels of mean prevalence . An exception was asthma symptoms in the older age-group , in which decreases were more common at high prevalence . For both age-groups , more centres showed increases in all three disorders more often than showing decreases , but most centres had mixed changes . INTERPRETATION The rise in prevalence of symptoms in many centres is concerning , but the absence of increases in prevalence of asthma symptoms for centres with existing high prevalence in the older age-group is reassuring . The divergent trends in prevalence of symptoms of allergic diseases form the basis for further research into the causes of such disorders This study was design ed to assess the effectiveness of a high-efficiency particulate air ( HEPA ) filter in alleviating allergic respiratory symptoms . Thirty-two patients were studied who had symptomatic perennial rhinitis and /or asthma during the fall and winter months and had a positive skin test with house dust or house dust -- mite extract . An ENVIRACAIRE room air cleaner was placed in the bedroom for 8 weeks . In a r and om manner , the active filter was used for 4 weeks and a blank filter for 4 weeks . There was an average 70 % reduction in the particulate matter greater than or equal to 0.3 micron with the HEPA filter . In a double-blind design , results were assessed by analysis of the patients ' symptom/medication scores and subjective evaluation . For the total study , there was no difference in the total symptom/medication scores or individual symptom scores during the placebo and active-filter periods . Analysis of the last 2 weeks of each filter period in which respiratory infection was absent demonstrated definite differences in total and individual symptoms , suggesting active-filter benefit . Patients ' subjective responses also suggested benefit from the filter . The overall impression is that the HEPA filter can reduce allergic respiratory symptoms UNLABELLED The aim of this intervention study was to identify any health improvements in the upper and lower airways of office workers after the installation of local electrostatic air cleaners . Eighty persons with airways symptoms were recruited and r and omly assigned to an intervention or control group . Half of the air cleaners had a non-functioning electrostatic unit . Both participants and field research ers were blinded to the group status . Subjective symptoms were recorded using a question naire , and indexes calculated for general , irritation and skin symptoms . Objective respiratory health indicators were recorded , with acoustic rhinometry and peak expiratory flow ( PEF ) meters . In the intervention group there was a decrease in mean dust concentration from 65 to 35 microg/m(3 ) , and a reduction from 57 to 47 microg/m(3 ) in the control group ( P < 0.05 for difference in decline ) . The reduction was observed for all particles sizes . The irritation and general symptom indices decreased in both groups , but there was no improvement in the intervention group , compared with the control group . Median PEF increased 3 ml/s in the intervention group , and decreased 4 ml/s in the control group . The adjusted odds ratio for an increase above the 70th percentile was 5.7 ( 95 % CI 1.0 - 32 ) . PRACTICAL IMPLICATION S Electrostatic air cleaners can reduce the dust concentration effectively in the office environment . Small , medium and large sized particles can be reduced by approximately 50 % , relatively most effectively for the respirable particles . However , the air cleaners tested in this study produced an annoying fan noise . Cleaning efficiency and noise data should be given consideration before installation . This experimental field study suggests that office workers with airways symptoms may benefit from installation of local electrostatic air cleaners N-(3,4-dimethoxycinnamoyl ) anthranilic acid ( N-5 ' ) , a new orally useable mast cell stabilizer , was investigated for its efficacy , safety and usefulness in the treatment of 302 patients with perennial nasal allergy by an intergroup , double-blind comparative test using disodium cromoglycate ( DSCG ) and an inactive placebo as control . The results indicated that N-5 ' , as a mild mast cell stabilizer , was comparable to DSCG in efficacy and minimum in side effect The efficacy of an air‐cleaning device equipped with a high efficiency particulate air ( HEPA ) filter ( without further avoidance measures ) was studied in patients allergic to house dust mite . The effects of the air‐cleaner on indoor Dermatophagoides sp. levels , symptom score and bronchial hyperresponsiveness in nine mite‐allergic patients were assessed using a cross‐over controlled study . No significant effect was demonstrated on indoor Dermatophagoides sp. levels when comparing the period of air‐cleaner activity ( 2 months ) with the control period ( 2 months ) . The Dermatophagoides sp. levels in the houses studied were lower than the risk level for asthmatic attacks , making it difficult to assess any effect on asthma ; however , neither bronchial hyperresponsiveness nor rhinitis symptom score were changed by air‐cleaner activity . During the trial period , however the mean level of Dermatophagoides sp. allergen in the houses changed spontaneously from 4.4 Hg/g ( mean level in the first 2 trial months ) to 1 . 75 μg/g of dust ( second 2 months ) ( P < 0.05 ) . Owing to this change , the mean rhinitis symptom score also decreased ( P < 0.05 ) , even if no significant correlation was demonstrated ( r = 0.4 P= 0.089 ) . HEPA filter air‐cleaners appear insufficient as substitutes for st and ard avoidance measures in mite allergic patients Inheritance and allergen exposure are key factors in the development and the course of atopic allergy , expressed as conjunctivitis , rhinitis , asthma or dermatitis . This study concerns the clinical significance of mite and mite‐allergen avoidance measures based on intensive cleaning with acaricide ( solidified benzylbenzoate ) added ( 10 dwellings ) , and without biocidal activity ( 10 other homes ) as a control in a double‐blind trial with matched pairs . Twenty subjects with persisting rhinitic complaints were selected . They lived in 20 different dwellings and were ail sensitized to pyroglyphid mites ; 12 of them were also sensitized to stored product miles ( Acari ) . Daily symptoms and medication score , guanine and dust exposure , total and mite‐specific IgE in serum , eosinophilia in the blood and in the nasal smear , intracutaneous tests with house dust mite and storage mite extracts were compared in both pairs and groups . Acarological data , physiochemical aspects and exposure assessment are discussed in detail elsewhere . Symptom scores dropped significantly , as did the total IgE and exposure to dust and mite products in the acaricidal cleaner treatment group . After 1 year , the daily symptoms median was 47 % ( P= 0.025 ) , total IgE was 38 % ( P=0.0049 ) , and exposure to dust and mite products ( guanine exposure ) was 53 % ( P= 0.0449 ) better or lower than in the controls . Intensive cleaning , without acaricidal treatment performed twice a year , result ed in clinical improvement in four out of 10 subjects , of whom none became free of complaints . In the Acarosan treatment group ( cleaning+ benzylbenzoate ) eight out of 10 subjcets improved , in three cases subjective symptoms disappeared . The conclusion is that mite avoidance in homes can be carried out successfully with a special acaricidal cleaning formulation Acarosan We report on the mechanisms , the environmental changes and patient compliance with regard to conventional and new dust and mite avoidance measures to prevent allergic symptoms caused by mite allergens , taking into account both allergen contamination and the developmental success of pyroglyph Output:	House dust mite impermeable bedding as an isolated intervention is unlikely to offer clinical benefit . Trials to date have on the whole been small and of poor method ological quality , making it difficult to offer any definitive recommendations on the role , if any , of house dust mite avoidance measures in the management of house dust mite sensitive perennial allergic rhinitis . The results of these studies suggest that use of acaricides and extensive bedroom-based environmental control programmes may be of some benefit in reducing rhinitis symptoms and , if considered appropriate , these should be the interventions of choice . Isolated use of house dust mite impermeable bedding is unlikely to prove effective
MS21602	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Hypertension is the most prevalent comorbidity after heart transplantation ( HT ) . Exercise training ( ET ) is widely recommended as a key non-pharmacologic intervention for the prevention and management of hypertension , but its effects on ambulatory blood pressure ( ABP ) and some mechanisms involved in the pathophysiology of hypertension have not been studied in this population . The primary purpose of this study was to investigate the effects of ET on ABP and arterial stiffness of HT recipients . METHODS 40 HT patients , r and omized to ET ( n = 31 ) or a control group ( n = 9 ) underwent a maximal grade d exercise test , 24-hour ABP monitoring , and carotid-femoral pulse wave velocity ( PWV ) assessment before the intervention and at a 12-week follow-up assessment . The ET program was performed thrice-weekly and consisted primarily of endurance exercise ( 40 minutes ) at ~70 % of maximum oxygen uptake ( Vo2MAX ) . RESULTS The ET group had reduced 24-hour ( 4.0 ± 1.4 mm Hg , p < 0.01 ) and daytime ( 4.8 ± 1.6 mm Hg , p < 0.01 ) systolic ABP , and 24-hour ( 7.0 ± 1.4 mm Hg , p < 0.001 ) daytime ( 7.5 ± 1.6 mm Hg , p < 0.001 ) and nighttime ( 5.9 ± 1.5 mm Hg , p < 0.001 ) diastolic ABP after the intervention . The ET group also had improved Vo2MAX ( 9.7 % ± 2.6 % , p < 0.001 ) after the intervention . However , PWV did not change after ET . No variable was changed in the control group after the intervention . CONCLUSIONS The 12-week ET program was effective for reducing ABP but not PWV in heart transplant recipients . This result suggests that endurance ET may be a tool to counteract hypertension in this high-risk population In heart transplant ( HTx ) recipients , there has been reluctance to recommend high‐intensity interval training ( HIIT ) due to denervation and chronotropic impairment of the heart . We compared the effects of 12 weeks ' HIIT versus continued moderate exercise ( CON ) on exercise capacity and chronotropic response in stable HTx recipients > 12 months after transplantation in a r and omized crossover trial . The study was completed by 16 HTx recipients ( mean age 52 years , 75 % males ) . Baseline peak oxygen uptake ( VO2peak ) was 22.9 mL/kg/min . HIIT increased VO2peak by 4.9 ± 2.7 mL/min/kg ( 17 % ) and CON by 2.6 ± 2.2 mL/kg/min ( 10 % ) ( significantly higher in HIIT ; p < 0.001 ) . During HIIT , systolic blood pressure decreased significantly ( p = 0.037 ) with no significant change in CON ( p = 0.241 ; between group difference p = 0.027 ) . Peak heart rate ( HRpeak ) increased significantly by 4.3 beats per minute ( p = 0.014 ) after HIIT with no significant change in CON ( p = 0.34 ; between group difference p = 0.027 ) . Heart rate recovery ( HRrecovery ) improved in both groups with a trend toward greater improvement after HIIT . The 5‐month washout showed a significant loss of improvement . HIIT was well tolerated , had a superior effect on oxygen uptake , and led to an unexpected increase in HRpeak accompanied by a faster HRrecovery . This indicates that the benefits of HIIT are partly a result of improved chronotropic response Background Aerobic exercise training improves vasodilatory capacity of peripheral resistance vasculature and modifies plasma proinflammatory markers in chronic heart failure patients . It is , however , currently unknown whether aerobic exercise has a similar effect in heart transplant recipients ( HTR ) . Design and Methods Eight weeks after transplantation , 14 HTR were r and omly assigned to 12 weeks of supervised aerobic exercise training ( TRAINED ; n = 8) or attention-time control ( CONTROL ; n = 6 ) in addition to posttransplantation medical care . Peak forearm blood flow and calf blood flow ( CBF ) during reactive hyperemia after 5 min of limb ischemia was used as a measure of endothelium-dependent vasodilation of limb resistance arteries . Plasma C-reactive protein , interleukin-6 ( IL-6 ) , tumor necrosis factor-alpha ( TNF-α ) , soluble intercellular adhesion molecule-1 ( sICAM-1 ) , and exercise capacity were measured at baseline and again after 12 weeks in both groups . Results Peak CBF increased 22 % in the TRAINED ( 25.9±5.8 - 31.6±7.9 ml/min/100 ml , P<0.05 ) , but there was no change in peak CBF after 12 weeks in CONTROL . Plasma C-reactive protein , IL-6 , TNF-α , sICAM-1 did not change in TRAINED , but there was a significant increase in TNF-α ( 1.66±1.02 vs. 3.07± 1.10 pg/ml , P < 0.05 ) , and sICAM-1 ( 205.9±59.1 vs. 245.0 ± 47.9 ng/ml , P<0.01 ) in CONTROL after 12 weeks . Furthermore , exercise test duration improved 51.7 % ( P<0.01 ) and there was a trend toward an increase in peak VO2 ( P = 0.05 ) in TRAINED after 12 weeks but neither changed in CONTROL . Conclusion A program of supervised aerobic exercise improves endothelium-dependent vasodilation of the calf , but not forearm resistance arteries , and may attenuate a progressive increase in selected proinflammatory markers in HTR Aim To evaluate the effects of home- and hospital-exercise programs on exercise capacity and chronotropic variables in patients with heart transplantation . Methods Forty patients were r and omized into two groups either hospital- or home-based exercise program . The patients were compared , before and after the rehabilitation program , with respect to maximal oxygen uptake ( pVO2 ) , chronotropic variables [ heart rate reserve ( HRRe ) , heart rate recovery ( HRR1 ) , and chronotropic response index ( CRI ) ] and Duke Treadmill Score ( DTS ) . Results Hospital-based exercise group has shown a significant recovery in post-exercise pVO2 ( pre-exercise 16.73 ± 3.9 ml/kg/min , post-exercise 19.53 ± 3.89 ml/kg/min , P = 0.002 ) and DTS ( pre-exercise 4.74 ± 1.17 , post-exercise 5.61 ± 1.11 , P = 0.002 ) . A significant recovery in favor of the hospital-based exercise group was found in HRRe ( pre-exercise 26.9 ± 14.6 , post-exercise 34.6 ± 14.6 , P = 0.01 ) . No significant change was observed in HRR1 ( pre-exercise −1.38 ± 1.04 , post-exercise −1.21 ± 1.89 , P = 0.49 ) and CRI ( pre-exercise 0.44 ± 0.23 , post-exercise 0.48 ± 0.20 , P = 0.15 ) in hospital-based exercise group . No significant change was observed in any parameters of home-based group ( P > 0.05 ) . Conclusion A significant recovery was observed both in the functional capacity and the chronotropic response in hospital-based exercise program . Exercise programs that are planned to be performed under supervision in rehabilitation units are useful for the patients with heart transplant in terms of the exercise capacity and chronotropic variables OBJECTIVE To compare the effects of two physical therapy exercise in-hospital programs in pulmonary function and functional capacity of patients in the postoperative period of heart transplantation . METHODS Twenty-two heart transplanted patients were r and omized to the control group ( CG , n=11 ) and training group ( TG , n=11 ) . The control group conducted the exercise program adopted as routine in the institution and the training group has had a protocol consisting of 10 stages , with incremental exercises : breathing exercises , resistance training , stretching and walking . The programs began on the first day after extubation and stretched until hospital discharge . Assessed pulmonary function , distance walked in six minutes walk test ( 6MWT ) and peripheral muscle strength by one repetition maximum test ( 1RM ) . RESULTS Similar behavior was observed between the two groups treated , with statistically significant increases between the first and second test of the following variables : FVC ( 59 % in CG and 35.2 % in TG ) ; MIP ( 8.6 % in CG and 53.5 % in TG ) , MEP ( 28.8 % in CG and 40.7 % in TG ) and 6MWT ( 44.5 % in CG and 31.4 % in TG ) . There was an increase of peripheral strength by 1RM test , over time , to the muscle groups of the elbow flexors , shoulder flexors , hip abductors and knee flexors . CONCLUSION Heart transplant patients benefit from exercise programs in hospital , regardless of the program type applied . A new training proposal did not result in superiority compared to routine programme applied . Exercise protocol s provided improves in ventilatory variables and functional capacity of this population The aim of the review was to assess the effect of patient education in ischaemic heart disease . Thirteen r and omised controlled trials of moderate to good quality including 68,556 patients were selected . The effect on mortality , cardiac morbidity , hospitalisation and health-related quality of life was assessed and only non-significant tendencies of effect were found . The authors of the review nevertheless conclude that the review supports current rehabilitation programmes that include patient education . Further research in patient education , especially concerning the most effective methods of education delivery , is needed BACKGROUND Heart transplantation normalizes central hemodynamics , but endothelial dysfunction persists after transplantation . METHODS To investigate the effects of aerobic exercise on arterial function , oxidative stress , lipid profile , and sympathetic nervous system activity , 20 heart transplant recipients ( age , 54.3 + /- 9.1 years ; 17 men , 3 women ) were r and omly assigned to 12 weeks of supervised treadmill exercise ( Trained ; n = 10 ) or st and ard medical care ( Control ; n = 10 ) . Supervised exercise was initiated at 8 weeks after transplant . Brachial artery reactivity was assessed using flow-mediated dilation . RESULTS The VO2 peak increased 26 % in the Trained patients ( 15.4 + /- 4.3 vs 19.4 + /- 5.5 ml/kg/min ; p < or = 0.05 ) but did not change in the Controls ( 16.2 + /- 5.2 vs 16.8 + /- 2.8 ml/kg/min ; p > or = 0.05 ) . Brachial artery flow-mediated dilation ( 10.1 % + /- 6.1 % vs 9.6 % + /- 6.2 % ) and absolute brachial diameter ( 0.48 + /- 0.22 vs 0.42 + /- 0.24 mm ) did not change in Trained patients , but brachial flow-mediated dilation ( 10.5 % + /- 2.8 % vs 7.9 % + /- 5.1 % ) and the absolute change in brachial diameter ( 0.48 + /- 0.16 vs 0.36 + /- 0.24 mm ) decreased significantly ( p < or = 0.05 ) in the Control patients . Resting norepinephrine decreased significantly ( p < or = 0.05 ) after training ( 0.32 + /- 0.19 vs 0.22 + /- 0.22 ng/ml ) , but there was a nonsignificant trend toward increased norepinephrine in the Controls ( 0.26 + /- 0.17 vs 0.53 + /- 0.41 ng/ml ; p = 0.07 ) . The lipid profile and marker of oxidative stress did not differ between the groups before or after the intervention . CONCLUSIONS To our knowledge , this is the first prospect i ve , r and omized study to investigate the effects of heart transplantation and aerobic exercise on peripheral artery function in the same cohort of heart transplant recipients . Brachial artery flow-mediated dilation increased early in the post-operative period . Aerobic exercise preserved but did not improve brachial artery flow-mediated dilation . Heart transplant recipients who did not participate in supervised exercise showed a progressive decline in brachial artery flow-mediated dilation Longterm treatment after heart transplantation ( HTX ) improves survival , although the quality of life and exercise tolerance decreased continuously between one and ten years after transplantation . The role of physical exercise and psychological support in longterm treatment after HTX has not been determined . We analyzed the effects of a one year outpatient rehabilitation program in combination with a home based , computer assisted training program on exercise Output:	One adverse event was reported by one study .Exercise-based cardiac rehabilitation improves exercise capacity , but exercise was found to have no impact on health-related quality of life in the short-term ( median 12 weeks follow-up ) , in heart transplant recipients whose health is stable . There was no evidence of statistical heterogeneity across trials for exercise capacity and no evidence of small study bias . We found moderate quality evidence suggesting that exercise-based cardiac rehabilitation improves exercise capacity , and that exercise has no impact on health-related quality of life in the short-term ( median 12 weeks follow-up ) , in heart transplant recipients .
MS21603	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Numerous r and omized , double-blind , placebo-controlled studies and observational studies have shown that statins reduce mortality and major cardiovascular events in older high-risk persons with hypercholesterolemia . The Heart Protection Study showed that statins reduced mortality and major cardiovascular events in high-risk persons regardless of the initial level of serum lipids , age , or gender . The up date d National Cholesterol Education Program III guidelines state that in very high-risk persons , a serum low-density lipoprotein ( LDL ) cholesterol level of < 70 mg/dl ( 1.8 mmol/l ) is a reasonable clinical strategy for moderately high-risk persons ( 2 or more risk factors and a 10-year risk for coronary artery disease of 10 % to 20 % ) , and the serum LDL cholesterol should be reduced to < 100 mg/dl ( 2.6 mmol/l ) . When LDL cholesterol-lowering drug therapy is used to treat high-risk persons or moderately high-risk persons , the serum LDL cholesterol should be reduced by at least 30 % to 40 % . The serum LDL cholesterol should be decreased to less than 160 mg/dl in persons at low risk for cardiovascular disease . Addition of other lipid-lowering drugs to statin therapy has not been demonstrated to further reduce cardiovascular events and mortality Summary Purpose Pre clinical data has demonstrated the potential of simvastatin to overcome cetuximab resistance in KRAS mutant CRC patients . Therefore , we design ed a study using simvastatin/cetuximab/irinotecan for KRAS mutant CRC patients who are refractory to irinotecan and oxaliplatin-based chemotherapy . Patients and methods In this phase II study , patients received 500 mg/m2 cetuximab , 150–180 mg/m2 ( day 1 ) , and 80 mg simvastatin ( once daily , days 1–14 , every 2 weeks ) . The primary endpoint was the objective response rate ( ORR ) . Secondary endpoints were progression-free survival ( PFS ) , overall survival ( OS ) , the disease control rate ( DCR ) , and safety . We also analyzed the relationship between the RAS gene expression signature score and treatment response to simvastatin/cetuximab/irinotecan . Results Fifty-two KRAS mutant CRC patients were enrolled . The ORR ( complete response [ CR ] , 0 ; partial response [ PR ] , 1 ) was 1.9 % ( 95 % confidence interval [ CI ] , −1.8–5.6 ) . The DCR ( CR , 0 ; PR , 1 ; stable disease , 33 ) was 65.4 % ( 95 % CI , 52.5–78.3 ) . The median PFS and OS from the time of study drug administration were 7·6 months ( 95 % CI , 4.4–10.8 ) and 12.8 months ( 95 % CI , 9.5–16.2 ) , respectively . The most common grade 3/4 adverse events were anemia ( 28.8 % ) , neutropenia ( 13.5 % ) , and diarrhea ( 7.7 % ) . The RAS signature score was significantly correlated with the maximal change in target lesions from baseline ( r = 0.57 , P = 0.014 ) . Conclusion The simvastatin/cetuximab/irinotecan regimen showed promising efficacy and safety in KRAS mutant CRC patients who failed irinotecan and oxaliplatin-based chemotherapy . The RAS signature may be a novel predictor of treatment response to cetuximab-combined chemotherapy in CRC patients Importance Patients with cancer who use statins appear to have a substantially better survival than nonusers in observational studies . However , this inverse association between statin use and mortality may be due to selection bias and immortal-time bias . Objective To emulate a r and omized trial of statin therapy initiation that is free of selection bias and immortal-time bias . Design , Setting , and Participants We used observational data on 17 372 patients with cancer from the Surveillance , Epidemiology , and End Results (SEER)-Medicare data base ( 2007 - 2009 ) with complete follow-up until 2011 . The SEER-Medicare data base links 17 US cancer registries and cl aims files from Medicare and Medicaid in 12 US states . We included individuals with a new diagnosis of colorectal , breast , prostate , or bladder cancer who had not been prescribed statins for at least 6 months before the cancer diagnosis . Individuals were duplicated , and each replicate was assigned to either the strategy “ statin therapy initiation within 6 months after diagnosis ” or “ no statin therapy initiation . ” Replicates were censored when they stopped following their assigned strategy , and the potential selection bias was adjusted for via inverse-probability weighting . Hazard ratios ( HRs ) , cumulative incidences , and risk differences were calculated for all-cause mortality and cancer-specific mortality . We then compared our estimates with those obtained using the same analytic approaches used in previous observational studies . Exposures Statin therapy initiation within 6 months after cancer diagnosis . Main Outcomes and Measures Cancer-specific and all-cause mortality using SEER-Medicare data and data from previous studies . Results Of the 17 372 patients whose data were analyzed , 8440 ( 49 % ) were men , and 8932 ( 51 % ) were women ( mean [ SD ] age , 76.4 [ 7.4 ] years ; range , 66 - 115 years ) . The adjusted HR ( 95 % CI ) comparing statin therapy initiation vs no initiation was 1.00 ( 0.88 - 1.15 ) for cancer-specific mortality and 1.07 ( 0.93 - 1.21 ) for overall mortality . Cumulative incidence curves for both groups were almost overlapping ( the risk difference never exceeded 0.8 % ) . In contrast , the methods used by prior studies result ed in an inverse association between statin use and mortality ( pooled hazard ratio 0.69 ) . Conclusion and Relevance After using methods that are not susceptible to selection bias from prevalent users and to immortal time bias , we found that initiation of therapy with statins within 6 months after cancer diagnosis did not appear to improve 3-year cancer-specific or overall survival BACKGROUND & AIMS Statin use has been associated with a reduced incidence of colorectal cancer and might also affect survival of patients diagnosed with colon cancer . Statins are believed to inhibit Ras signaling and may also activate the bone morphogenetic protein ( BMP ) signaling pathway in colorectal cancer cells . We investigated the effects of statins on overall survival of patients with a diagnosis of colon cancer , and whether their effects were associated with changes in KRAS or the BMP signaling pathways . METHODS Data were derived from the PHARMO data base network ( Netherl and s ) and linked to patients diagnosed with colon cancer from 2002 through 2007 , listed in the Eindhoven Cancer Registry . We obtained information on causes of death from statistics Netherl and s. We constructed a tissue microarray of 999 colon cancer specimens from patients who underwent surgical resection from 2002 through 2008 . Survival was analyzed with statin user status after diagnosis as a time-dependent covariate . Multivariable Poisson regression survival models and Cox analyses were used to study the effect of statins on survival . Tumor tissues were analyzed by immunohistochemistry for levels of SMAD4 , BMPR1A , BMPR1B , and BMPR2 proteins . Tumor tissues were considered to have intact BMP signaling if they contained SMAD4 plus BMPR1A , BMPR1B , or BMPR2 . DNA was isolated from tumor tissues and analyzed by quantitative polymerase chain reaction to detect mutations in KRAS . The primary outcome measures were overall mortality and cancer-specific mortality . RESULTS In this cohort , 21.0 % of the patients ( 210/999 ) were defined as statin users after diagnosis of colon cancer . Statin use after diagnosis was significantly associated with reduced risk of death from any cause ( adjusted relative risk [ RR ] , 0.67 ; 95 % confidence interval [ CI ] , 0.51 - 0.87 ; P = .003 ) and death from cancer ( adjusted RR , 0.66 ; 95 % CI , 0.49 - 0.89 ; P = .007 ) . Statin use after diagnosis was associated with reduced risk of death from any cause or from cancer for patients whose tumors had intact BMP signaling ( adjusted RR , 0.39 ; 95 % CI , 0.22 - 0.68 ; P = .001 ) , but not for patients whose tumors did not have BMP signaling ( adjusted RR , 0.81 ; 95 % CI , 0.55 - 1.21 ; P = .106 ; P < .0001 for the interaction ) . Statin use after diagnosis was not associated with reduced risk of death from any cause or from cancer for patients whose tumors did not contain KRAS mutations ( adjusted RR , 0.81 ; 95 % CI , 0.56 - 1.18 ; P = .273 ) or whose tumors did have KRAS mutations ( adjusted RR , 0.59 ; 95 % CI 0.35 - 1.03 ; P = .062 ; P = .90 for the interaction ) . CONCLUSIONS In an analysis of 999 patients with a diagnosis of colon cancer , we associated statin with reduced risk of death from any cause or from cancer . The benefit of statin use is greater for patients whose tumors have intact BMP signaling , independent of KRAS mutation status . R and omized controlled trials are required to confirm these results BACKGROUND Atorvastatin , rosuvastatin and pitavastatin are available for intensive , aggressive low-density lipoprotein cholesterol (LDL-C)-lowering therapy in clinical practice . The objective of the R and omized Head-to-Head Comparison of Pitavastatin , Atorvastatin , and Rosuvastatin for Safety and Efficacy ( Quantity and Quality of LDL ) ( PATROL ) Trial was to compare the safety and efficacy of atorvastatin , rosuvastatin and pitavastatin head to head in patients with hypercholesterolemia . This is the first prospect i ve r and omized multi-center trial to compare these strong statins ( UMIN Registration No : 000000586 ) . METHODS AND RESULTS Patients with risk factors for coronary artery disease and elevated LDL-C levels were r and omized to receive atorvastatin ( 10mg/day ) , rosuvastatin ( 2.5mg/day ) , or pitavastatin ( 2mg/day ) for 16 weeks . Safety was assessed in terms of adverse event rates , including abnormal clinical laboratory variables related to liver and kidney function and skeletal muscle . Efficacy was assessed by the changes in the levels and patterns of lipoproteins . Three hundred and two patients ( from 51 centers ) were enrolled , and these 3 strong statins equally reduced LDL-C and LDL particles , as well as fast-migrating LDL ( modified LDL ) by 40 - 45 % . Newly developed pitavastatin was non-inferior to the other 2 statins in lowering LDL-C. There were no differences in the rate of adverse drug reactions among the 3 groups , but HbA(1c ) was increased while uric acid was decreased in the atorvastatin and rosuvastatin groups . CONCLUSIONS The safety and efficacy of these 3 strong statins are equal . It is suggested that the use of these 3 statins be completely dependent on physician discretion based on patient background BACKGROUND Several studies have indicated that statins may have anticarcinogenic effects . The aim of the present study was to investigate if statin treatment was associated with a reduced risk of hepatocellular carcinoma ( HCC ) or colon cancer . METHODS A nationwide case-control study was carried out in which all cases of HCC and colon cancer in the Swedish population above 40 years of age between 1 July 2006 and 31 December 2010 were identified in the Swedish Cancer Register . For every case , five controls were selected and matched on age and sex . Data on statin use was extracted from the Swedish Prescribed Drug Register . We estimated risks using conditional logistic regression and adjusted for educational level , concomitant medications and comorbidity . RESULTS Identified were 3994 cases of HCC and matched with 19.970 controls , and 21.143 cases of colon cancer were identified and matched with 105.715 controls . In the adjusted analysis , the odds ratio ( OR ) for HCC among statin users was 0.88 ( 95 % confidence interval ( CI ) 0.81 - 0.96 ) , and the OR for colon cancer was 1.04 ( 95%CI 1.00 - 1.08 ) compared with non-users . CONCLUSION Statin use was associated with a modest decreased risk of HCC but did not influence the risk of colon cancer . Future r and omized placebo-controlled trials in HCC high-risk patients are warranted to further investigate the possible prophylactic effect of statins in HCC Pre clinical data showed anticancer effects of statins in melanoma , but meta‐analyses could not demonstrate a reduced melanoma incidence in statin users . Output:	In vitro and animal studies have shown a potential chemopreventive effect of statins and their efficacy in adjuvant therapy of colorectal cancer . Statins also show a potential role in chemoprevention of colorectal cancer in patients with inflammatory bowel disease . CONCLUSIONS Accumulating evidence suggests that statins may have a role in colorectal cancer prevention and treatment .
MS21604	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Purpose Pegfilgrastim is a pegylated form of filgrastim , a recombinant protein of granulocyte colony-stimulating factor , that is used to reduce the risk of febrile neutropenia ( FN ) . Here , we report the results of a phase III trial of pegfilgrastim in breast cancer patients receiving docetaxel and cyclophosphamide ( TC ) chemotherapy . Methods We conducted a double-blind , placebo-controlled , r and omized trial to determine the efficacy of pegfilgrastim in reducing the risk of FN in early-stage breast cancer patients . A total of 351 women ( 177 in the pegfilgrastim group and 174 in the placebo group ) between 20 and 69 years of age with stage I – III invasive breast carcinoma who were to receive TC chemotherapy ( docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks ) as either neoadjuvant or adjuvant therapy were enrolled ; 346 of these patients were treated with either pegfilgrastim ( n = 173 ) or placebo ( n = 173 ) . Results The incidence of FN was significantly lower in the pegfilgrastim group than in the placebo group ( 1.2 vs. 68.8 % , respectively ; P < 0.001 ) . In addition , patients in the pegfilgrastim group required less hospitalization and antibiotics for FN . Most adverse events were consistent with those expected for breast cancer subjects receiving TC chemotherapy . Conclusions Pegfilgrastim is safe and significantly reduces the incidence of FN in breast cancer patients Purpose Lipegfilgrastim is a once-per-cycle , fixed-dose , glycoPEGylated recombinant granulocyte colony-stimulating factor ( G-CSF ) recently approved in Europe to reduce the duration of chemotherapy-induced neutropenia and incidence of febrile neutropenia in patients with cancer receiving chemotherapy . Bone pain-related ( BPR ) adverse events are commonly associated with G-CSF therapy . This post hoc analysis examined BPR treatment-emergent adverse events ( TEAEs ) in two comparative studies of lipegfilgrastim or pegfilgrastim in patients receiving chemotherapy . Methods A post hoc analysis was conducted using integrated data from two double-blind r and omized studies in patients with breast cancer receiving docetaxel and doxorubicin and treated prophylactically with subcutaneous lipegfilgrastim 6 mg or pegfilgrastim 6 mg once per cycle . BPR TEAEs were defined as arthralgia , back pain , bone pain , musculoskeletal chest pain , musculoskeletal discomfort , musculoskeletal pain , myalgia , neck pain , noncardiac chest pain , and pain in extremity . Relationship of BPR TEAEs to study treatment or chemotherapy was also reported by the investigators . Results The analysis included 306 patients ( lipegfilgrastim : n = 151 ; pegfilgrastim : n = 155 ) . The proportion of patients experiencing BPR TEAEs was similar with lipegfilgrastim and pegfilgrastim ( 25.2 vs 21.9 % , respectively ) , as was the proportion of patients experiencing BPR treatment-emergent adverse drug reactions ( TEADRs ) ( 18.5 vs 16.8 % , respectively ) . No BPR TEADRs were serious , and none led to discontinuation . Conclusions Nonsevere BPR TEAEs and TEADRs were observed in patients with breast cancer receiving chemotherapy and G-CSF ; rates of BPR events were similar between lipegfilgrastim and pegfilgrastim . The similar BPR safety profile of lipegfilgrastim and pegfilgrastim provides support for use in patients with breast cancer receiving chemotherapy After informed consent , 86 patients with advanced cancer undergoing potentially myelosuppressive cytotoxic chemotherapy were r and omized to receive placebo or subcutaneous granulocyte-colony stimulating factor ( G-CSF ) 5 micrograms/Kg/day in order to prevent severe neutropenia and its related morbidity . The incidence of neutropenia ( absolute neutrophil count < 1,000/mm3 ) was significantly reduced in patients receiving G-CSF than in controls ( 18 % versus 42 % ; P < 0.05 ) . The duration of neutropenia was also shortened by the administration of G-CSF ( 4.8 versus 8.2 days ; P < 0.05 ) . Therapy with G-CSF has also a positive impact on the dose-intensity of employed regimens . Patients treated with G-CSF showed oral fungal disease in 9 % of cases , while control patients had a 21 % incidence ( NS ) . Patients treated with G-CSF received 91 % of the programmed dose-intensity as compared to 71 % of control patients ( P < 0.05 ) . These data strengthen the clinical usefulness of G-CSF in the prevention of chemotherapy-related neutropenia , infections , and reduction in dose-intensity . Further studies are required to establish if the increase in dose-intensity allowed by G-CSF treatment may positively influence the outcome of cancer patients Background Patients with acute myeloid leukemia ( AML ) are often neutropenic as a result of their disease . Furthermore , these patients typically experience profound neutropenia following induction and /or consolidation chemotherapy and this may result in serious , potentially life-threatening , infection . This r and omized , double-blind , phase 2 clinical trial compared the efficacy and tolerability of pegfilgrastim with filgrastim for assisting neutrophil recovery following induction and consolidation chemotherapy for de novo AML in patients with low-to-intermediate risk cytogenetics . Methods Patients ( n = 84 ) received one or two courses of st and ard induction chemotherapy ( idarubicin + cytarabine ) , followed by one course of consolidation therapy ( high-dose cytarabine ) if complete remission was achieved . They were r and omized to receive either single-dose pegfilgrastim 6 mg or daily filgrastim 5 μg/kg , beginning 24 hours after induction and consolidation chemotherapy . Results The median time to recovery from severe neutropenia was 22.0 days for both pegfilgrastim ( n = 42 ) and filgrastim ( n = 41 ) groups during Induction 1 ( difference 0.0 days ; 95 % CI : -1.9 to 1.9 ) . During Consolidation , recovery occurred after a median of 17.0 days for pegfilgrastim versus 16.5 days for filgrastim ( difference 0.5 days ; 95 % CI : -1.1 to 2.1 ) . Therapeutic pegfilgrastim serum concentrations were maintained throughout neutropenia . Pegfilgrastim was well tolerated , with an adverse event profile similar to that of filgrastim . Conclusion These data suggest no clinical ly meaningful difference between a single dose of pegfilgrastim and multiple daily doses of filgrastim for shortening the duration of severe neutropenia following chemotherapy in de novo AML patients with low-to-intermediate risk cytogenetics . Trial registration Clinical trials.gov BACKGROUND Neutropenia is common in patients receiving myelotoxic chemotherapy . Pegfilgrastim , a sustained- duration filgrastim is a once-per-cycle therapy for prophylactic neutrophil support . PATIENTS AND METHODS Women , treated with four cycles of doxorubicin/docetaxel chemotherapy every 21 days , received pegfilgrastim or filgrastim 24 h after chemotherapy as a single subcutaneous injection per chemotherapy cycle ( pegfilgrastim 30 , 60 or 100 microg/kg ) or daily subcutaneous injections ( filgrastim 5 microg/kg/day ) . Safety , efficacy and pharmacokinetics were analyzed . RESULTS The incidence of grade 4 neutropenia in cycle 1 was 95 , 90 and 74 % , in patients who received pegfilgrastim 30 , 60 and 100 microg/kg , respectively , and 76 % in patients who received filgrastim . Mean duration of grade 4 neutropenia in cycle 1 was 2.7,2 and 1.3 days for doses of pegfilgrastim , and 1.6 days for filgrastim . The pharmacokinetics of pegfilgrastim were non-linear and dependent on both dose and neutrophil count . Pegfilgrastim serum concentration was sustained until the neutrophil nadir occurred then declined rapidly as neutrophils started to recover , consistent with a self-regulating neutrophil-mediated clearance mechanism . The safety profiles of pegfilgrastim and filgrastim were similar . CONCLUSIONS A single subcutaneous injection of pegfilgrastim 100 microg/kg provided neutrophil support and a safety profile comparable to daily subcutaneous injections of filgrastim during multiple chemotherapy cycles Sepsis associated with neutropenia remains a major cause of morbidity and mortality from many chemotherapy regimens . In a recent tabulation of commonly used chemotherapy agents [ 1 ] , 29 of 37 are listed as causing marked or moderate leukopenia . A known correlation exists between the degree and duration of neutropenia and the risk for sepsis [ 2 ] . In conjunction with neutropenia , infections with gram-negative organisms such as Pseudomonas spp . occur relatively frequently and have high morbidity and mortality rates if antibiotic therapy is not begun until infection is microbiologically confirmed [ 3 , 4 ] . Current recommended practice is to initiate empiric , broad-spectrum intravenous antibiotic therapy in all patients with febrile neutropenia at the onset of fever , despite clinical and microbiological evidence of infection being found in only 40 % to 60 % of cases [ 5 ] . In addition to antibiotic therapy , neutrophil recovery is an important factor for a successful treatment outcome in these patients [ 6 , 7 ] and has been identified as the most favorable prognostic factor in a recent multivariate logistic regression analysis of 14 variables analyzed in a study of antibiotic efficacy [ 7 ] . Granulocyte transfusions are logistically difficult , are associated with substantial toxicity , and are of uncertain efficacy [ 8 , 9 ] ; before the availability of the colony-stimulating factors , few pharmacologic agents had clinical utility in increasing neutrophil levels [ 10 ] . Filgrastim ( previously known as recombinant methionyl human granulocyte colony-stimulating factor [ r-metHuG-CSF ] ) is a hematopoietic growth factor that promotes the survival , proliferation , differentiation , and function of progenitor and mature cells of the neutrophil granulocyte lineage [ 11 ] . It has potent granulopoietic effects in vivo [ 12 - 14 ] , and its clinical pharmacology has been defined [ 15 ] . In two phase III studies [ 16 , 17 ] , filgrastim therapy that was started 1 day after chemotherapy reduced the severity and duration of neutropenia and decreased by nearly half the incidence of febrile neutropenic episodes and the average duration of hospitalization and antibiotic use per patient . The use of filgrastim to prevent febrile neutropenic episodes in patients with cancer who receive chemotherapy is now an approved indication in many countries . Not all patients with cancer who have had chemotherapy and who have been treated with filgrastim receive it to reduce the risk for neutropenic sepsis . Approximately 14 % of filgrastim in the United States has been used to treat episodes of postchemotherapy febrile neutropenia after they occur rather than to prevent them ( unpublished market research data , Amgen , Inc. ) . To determine if filgrastim administered in addition to st and ard empiric inpatient antibiotic therapy was also beneficial in patients presenting with established fever and neutropenia , we conducted a multicenter , r and omized , double-blind , placebo-controlled study . This is the first report of a study assessing therapeutic intervention with filgrastim in this clinical setting . Methods We present the analysis of findings from 218 patients enrolled at four centers between October 1988 and February 1992 . The study drug was filgrastim , a recombinant human protein produced in Escherichia coli [ 18 ] and supplied by Amgen , Inc. , Thous and Oaks , California . Patients Eligible patients with febrile neutropenia were adults ( age 16 years ) receiving chemotherapy for histologically confirmed cancer other than myeloid leukemia who had an oral temperature of greater than 38.2 C and a neutrophil count less than 1.0 109/L. The neutrophil count included the number of b and s and polymorphonuclear forms counted in manual differentials from blood smears . Patients were ineligible if they were already receiving antibiotic therapy , if they had septic shock ( a systolic blood pressure of < 90 mm Hg , poor peripheral perfusion , and abnormal mentation ) , if they were receiving myeloablative chemotherapy with marrow transplantation support , if they had severe renal impairment ( serum creatinine level > 0.7 mM ) , abnormal liver function ( bilirubin > 5 times the upper limit of normal ) , were pregnant or breast-feeding , or had a history of allergic reactions to the study antibiotics . Patients could enter the r and omized trial only once . If subsequent episodes of fever and neutropenia developed , patients were offered open-label filgrastim therapy Output:	Mecapegfilgrastim , lipegfilgrastim and balugrastim might be the most appreciate G-CSF drugs with both good efficacy and tolerability when treating cancer patients after cytotoxic chemotherapy
MS21605	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The aim of the study was to analyse the toxicity and health related quality of life ( HRQoL ) of breast cancer patients treated with FAC ( 5-fluorouracil , doxorubicin , cyclophosphamide ) and TAC ( docetaxel , doxorubicin , cyclophosphamide ) with and without primary prophylactic G-CSF ( PPG ) . PATIENTS AND METHODS This was a phase III study to compare FAC and TAC as adjuvant treatment of high-risk node-negative breast cancer patients . After the entry of the first 237 patients , the protocol was amended to include PPG in the TAC arm due to the high incidence of febrile neutropenia . A total of 1047 evaluable patients from 49 centres in Spain , two in Pol and and four in Germany were included in the trial . Side-effects and the scores of the EORTC QLQ-C30 and QLQ BR-23 question naires were compared in the three groups ( FAC , TAC pre-amendment and TAC post-amendment ) . RESULTS The addition of PPG to TAC significantly reduced the incidence of neutropenic fever , grade 2 - 4 anaemia , asthenia , anorexia , nail disorders , stomatitis , myalgia and dysgeusia . Patient QoL decreased during chemotherapy , more with TAC than FAC , but returned to baseline values afterwards . The addition of PPG to TAC significantly reduced the percentage of patients with clinical ly relevant Global Health Status deterioration ( 10 or more points over baseline value ) at the end of chemotherapy ( 64 % versus 46 % , P<0.03 ) . CONCLUSIONS The addition of PPG significantly reduces the incidence of neutropenic fever associated with TAC chemotherapy as well as that of some TAC-induced haematological and extrahaematological side-effects . The HRQoL of patients treated with TAC is worse than that of those treated with FAC but improves with the addition of PPG , particularly in the final part of chemotherapy treatment BACKGROUND Neutropenia is common in patients receiving myelotoxic chemotherapy . Pegfilgrastim , a sustained- duration filgrastim is a once-per-cycle therapy for prophylactic neutrophil support . PATIENTS AND METHODS Women , treated with four cycles of doxorubicin/docetaxel chemotherapy every 21 days , received pegfilgrastim or filgrastim 24 h after chemotherapy as a single subcutaneous injection per chemotherapy cycle ( pegfilgrastim 30 , 60 or 100 microg/kg ) or daily subcutaneous injections ( filgrastim 5 microg/kg/day ) . Safety , efficacy and pharmacokinetics were analyzed . RESULTS The incidence of grade 4 neutropenia in cycle 1 was 95 , 90 and 74 % , in patients who received pegfilgrastim 30 , 60 and 100 microg/kg , respectively , and 76 % in patients who received filgrastim . Mean duration of grade 4 neutropenia in cycle 1 was 2.7,2 and 1.3 days for doses of pegfilgrastim , and 1.6 days for filgrastim . The pharmacokinetics of pegfilgrastim were non-linear and dependent on both dose and neutrophil count . Pegfilgrastim serum concentration was sustained until the neutrophil nadir occurred then declined rapidly as neutrophils started to recover , consistent with a self-regulating neutrophil-mediated clearance mechanism . The safety profiles of pegfilgrastim and filgrastim were similar . CONCLUSIONS A single subcutaneous injection of pegfilgrastim 100 microg/kg provided neutrophil support and a safety profile comparable to daily subcutaneous injections of filgrastim during multiple chemotherapy cycles 632 Background : Following the BCIRG 001 , PACS 01 and HERA trials , this r and omised , multicentre , open-label , Phase III trial was design ed to demonstrate the benefit of concomitant docetaxel and epirubicin versus anthracyclines , and evaluate the use of sequential trastuzumab . METHODS Patients ( pts ) with localised , resectable , unilateral breast cancer who met the following criteria were eligible : age < 65 years , ≥1 positive node , M0 , adequate heart and organ functions . Pts were r and omised to receive either 6 cycles of 5-fluorouracil-epirubicin-cyclophosphamide ( FEC100 : F and C , 500 mg/m2 , E 100 mg/m2 ) ( Arm A ) or epirubicin-docetaxel ( ET75 : E 75 mg/m2 , T 75 mg/m2 ) ( Arm B ) . Primary prophylaxis with G-CSF was not planned . Radiotherapy was m and atory after conservative surgery and tamoxifen was required in pts with hormone receptor-positive tumours . Pts with HER2-positive disease were then further r and omised to observation only or to 1 year of trastuzumab monotherapy ( 6 mg/kg iv every 3 weeks ) . In HER2-positive pts receiving trastuzumab , left ventricular ejection fraction ( LVEF ) was determined at Cycles 2 , 4 , 8 , 13 , 18 and after 2 years . Otherwise , LVEF was determined at baseline and at 1 year post-surgery . RESULTS Of the 3010 pts recruited ( 2622 evaluable for safety to date ) , 1518 received FEC100 and 1492 received ET75 after the first r and omisation . Haematologic toxicity was the most frequent toxicity in both arms . Grade 3 - 4 toxicities were similar for Arms A and B , except febrile neutropenia ( 10.3 % and 31.4 % , respectively ) and nausea/vomiting ( 13.2 % and 7.5 % , respectively ) . Grade 2 clinical cardiac toxicity ( decreased LVEF ) was observed in 4 pts in Arm A and 5 in Arm B , with median LVEF scores of 63 % in both arms at the end of chemotherapy . HER2-positive pts ( n=500 ) were then r and omised to either receive trastuzumab ( n=259 ) or observation only ( n=241 ) . CONCLUSIONS These preliminary safety data indicate that FEC100 and ET75 were both well tolerated , with acceptable cardiac safety values . The trial is ongoing and further analysis regarding the use of trastuzumab in this setting will be presented . [ Table : see text ] BACKGROUND TAC ( docetaxel/doxorubicin/cyclophosphamide ) is associated with high incidences of grade 4 neutropenia and febrile neutropenia ( FN ) . This analysis compared the efficacies of four regimens for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC . PATIENTS AND METHODS Patients with stage T2-T4 primary breast cancer were scheduled to receive 6 - 8 cycles of TAC . Primary prophylaxis was : ciprofloxacin 500 mg orally twice daily on days 5 - 14 ( n = 253 patients ; 1478 cycles ) , daily granulocyte colony-stimulating factor ( G-CSF ) ( filgrastim 5 microg/kg/day or lenograstim 150 microg/m(2)/day ) on days 5 - 10 ( n = 377 ; 2400 cycles ) , pegfilgrastim 6 mg on day 2 ( n = 305 ; 1930 cycles ) , or pegfilgrastim plus ciprofloxacin ( n = 321 ; 1890 cycles ) . RESULTS Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN ( 5 % and 7 % versus 18 % and 22 % of patients ; all P < 0.001 ) , grade 4 neutropenia , and leukopenia . Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN ( P < 0.01 versus pegfilgrastim alone ) and fatal neutropenic events . CONCLUSION Ciprofloxacin alone , or daily G-CSF from day 5 - 10 ( as in common practice ) , provided suboptimal protection against FN and related toxic effects in patients receiving TAC . Pegfilgrastim was significantly more effective in this setting , especially if given with ciprofloxacin Background Recombinant granulocyte colony-stimulating factors ( G-CSFs ) such as Filgrastim are used to treat chemotherapy-induced neutropenia . We investigated a new G-CSF , XM02 , and compared it to Neupogen ™ after myelotoxic chemotherapy in breast cancer ( BC ) patients . Methods A total of 348 patients with BC receiving docetaxel/doxorubicin chemotherapy were r and omised to treatment with daily injections ( subcutaneous 5 μg/kg/day ) for at least 5 days and a maximum of 14 days in each cycle of XM02 ( n = 140 ) , Neupogen ™ ( n = 136 ) or placebo ( n = 72 ) . The primary endpoint was the duration of severe neutropenia ( DSN ) in cycle 1 . Results The mean DSN in cycle 1 was 1.1 , 1.1 , and 3.9 days in the XM02 , Neupogen ™ , and placebo group , respectively . Superiority of XM02 over placebo and equivalence of XM02 with Neupogen ™ could be demonstrated . Toxicities were similar between XM02 and Neupogen ™ . Conclusion XM02 was superior to placebo and equivalent to Neupogen ™ in reducing DSN after myelotoxic chemotherapy . Trial Registration Current Controlled Trials IS RCT PURPOSE We evaluated the efficacy of pegfilgrastim to reduce the incidence of febrile neutropenia associated with docetaxel in breast cancer patients . PATIENTS AND METHODS Patients were r and omly assigned to either placebo or pegfilgrastim 6 mg subcutaneously on day 2 of each 21-day chemotherapy cycle of 100 mg/m(2 ) docetaxel . The primary end point was the percentage of patients developing febrile neutropenia ( defined as body temperature > /= 38.2 degrees C and neutrophil count < 0.5 x 10(9)/L on the same day of the fever or the day after ) . Secondary end points were incidence of hospitalizations associated with a diagnosis of febrile neutropenia , intravenous ( IV ) anti-infectives required for febrile neutropenia , and the ability to maintain planned chemotherapy dose on time . Patients with febrile neutropenia were converted to open-label pegfilgrastim in subsequent cycles . RESULTS Nine hundred twenty-eight patients received placebo ( n = 465 ) or pegfilgrastim ( n = 463 ) . Patients receiving pegfilgrastim , compared with patients receiving placebo , had a lower incidence of febrile neutropenia ( 1 % v 17 % , respectively ; P < .001 ) , febrile neutropenia-related hospitalization ( 1 % v 14 % , respectively ; P < .001 ) , and use of IV anti-infectives ( 2 % v 10 % , respectively ; P < .001 ) . The percentage of patients receiving the planned dose on time was similar between patients receiving pegfilgrastim and patients who initially received placebo ( 80 % and 78 % , respectively ) , as would be expected of the study design . Pegfilgrastim was generally well tolerated and safe , and the adverse events reported were typical of this patient population . CONCLUSION First and subsequent cycle use of pegfilgrastim with a moderately myelosuppressive chemotherapy regimen markedly reduced febrile neutropenia , febrile neutropenia-related hospitalizations , and IV anti-infective use PURPOSE This multicenter , r and omized , double-blind , active-control study was design ed to determine whether a single subcutaneous injection of pegfilgrastim ( SD/01 , sustained- duration filgrastim ; 100 microg/kg ) is as safe and effective as daily filgrastim ( 5 microg/kg/d ) for reducing neutropenia in patients who received four cycles of myelosuppressive chemotherapy . PATIENTS AND METHODS Sixty-two centers enrolled 310 patients who received chemotherapy with docetaxel 75 mg/m(2 ) and doxorubicin 60 mg/m(2 ) on day 1 of each cycle for a maximum of four cycles . Patients were r and omized to receive on day 2 either a single subcutaneous injection of pegfilgrastim 100 microg/kg per chemotherapy cycle ( 154 patients ) or daily subcutaneous injections of filgrastim 5 microg/kg/d ( 156 patients ) . Absolute neutrophil count ( ANC ) , duration of grade 4 neutropenia , and safety parameters were monitored . RESULTS One dose of pegfilgrastim per chemotherapy cycle was comparable to daily subcutaneous injections of filgrastim with regard to all efficacy end points , including the duration of severe neutropenia and the depth of ANC nadir in all cycles . Febrile neutropenia across all cycles occurred Output:	Sensitivity analyses demonstrated that higher WTP threshold , younger age , earlier stage at diagnosis , or reduced G-CSF prices result in G-CSF prophylaxis being cost-effective at lower baseline FN risk levels . CONCLUSION Pegfilgrastim was the most cost-effective G-CSF . The most cost-effective strategy ( primary or secondary prophylaxis ) was dependent on the FN risk level for an individual patient , patient age and stage at diagnosis , and G-CSF price
MS21606	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE To evaluate safety and efficacy of combined transarterial chemoembolization ( TACE ) with doxorubicin-eluting beads ( DEB ) and sorafenib in patients with advanced hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS A prospect i ve single-center phase II study was undertaken involving patients with unresectable HCC . The protocol involved sorafenib 400 mg twice per day combined with DEB-TACE . Safety and response were assessed . Results DEB-TACE in combination with sorafenib was successfully administered in 35 patients : mean age , 63 years ; Child 's A , 89 % ; Barcelona Clinic Liver Cancer stage C , 64 % ; Eastern Cooperative Oncology Group performance status of 0 and 1 , 46 % and 54 % , respectively ; and mean index tumor size , 7.7 cm ( st and ard deviation , ± 4.2 cm ) . Patients underwent 128 cycles of therapy ( sorafenib plus DEB-TACE , 60 cycles ; sorafenib alone , 68 cycles ) . Median number of cycles per patient was two ( range , one to five cycles ) ; median number of days treated with sorafenib was 71 ( range , 4 to 620 days ) . The most common toxicities during cycle one were fatigue ( 94 % ) , anorexia ( 67 % ) , alterations in liver enzymes ( 64 % ) , and dermatologic adverse effects ( 48 % ) . Although most patients experienced at least one grade 3 to 4 toxicity , most toxicities were minor ( grade 1 to 2 , 83 % v grade 3 to 4 , 17 % ) . Toxicity during cycle two was decreased . Over the course of the study , there were 40 sorafenib dose interruptions and 25 sorafenib dose reductions . Sorafenib plus DEB-TACE was associated with a disease control rate of 95 % ( Response Evaluation Criteria in Solid Tumors Group)/100 % ( European Association for the Study of the Liver [ EASL ] ) , with an objective response of 58 % ( EASL ) . CONCLUSION The combination of sorafenib and DEB-TACE in patients with unresectable HCC is well tolerated and safe , with most toxicities related to sorafenib . Toxicity is manageable with dose adjustment of sorafenib . Preliminary efficacy data are promising PURPOSE This phase II study of sorafenib , an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases , assessed efficacy , toxicity , pharmacokinetics , and biomarkers in advanced hepatocellular carcinoma ( HCC ) patients . METHODS Patients with inoperable HCC , no prior systemic treatment , and Child-Pugh ( CP ) A or B , received continuous , oral sorafenib 400 mg bid in 4-week cycles . Tumor response was assessed every two cycles using modified WHO criteria . Sorafenib pharmacokinetics were measured in plasma sample s. Biomarker analysis included phosphorylated extracellular signal regulated kinase ( pERK ) in pretreatment biopsies ( immunohistochemistry ) and blood-cell RNA expression patterns in selected patients . RESULTS Of 137 patients treated ( male , 71 % ; median age , 69 years ) , 72 % had CP A , and 28 % had CP B. On the basis of independent assessment , three ( 2.2 % ) patients achieved a partial response , eight ( 5.8 % ) had a minor response , and 46 ( 33.6 % ) had stable disease for at least 16 weeks . Investigator-assessed median time to progression ( TTP ) was 4.2 months , and median overall survival was 9.2 months . Grade 3/4 drug-related toxicities included fatigue ( 9.5 % ) , diarrhea ( 8.0 % ) , and h and -foot skin reaction ( 5.1 % ) . There were no significant pharmacokinetic differences between CP A and B patients . Pretreatment tumor pERK levels correlated with TTP . A panel of 18 expressed genes was identified that distinguished " nonprogressors " from " progressors " with an estimated 100 % accuracy . CONCLUSION Although single-agent sorafenib has modest efficacy in HCC , the manageable toxicity and mechanisms of action support a role for combination regimens with other anticancer agents Until now , no effective systemic treatment options have been available for patients with unresectable advanced hepatocellular carcinoma ( HCC ) . In the Sorafenib Hepatocellular Carcinoma Assessment R and omized Protocol ( SHARP ) , patients with unresectable advanced HCC with Child – Pugh liver function class A and who had not received prior systemic therapy , received either oral sorafenib ( 400 mg twice daily ) or placebo until radiological and symptomatic progression . The two groups of patients were well balanced with respect to baseline characteristics . The study was stopped at the second planned interim analysis because of an advantage in the median overall survival ( 10.7 vs 7.9 months ; hazard ratio : 0.69 ; 95 % CI : 0.55–0.87 ; p < 0.001 ) and the median time to radiological progression ( 5.5 vs 2.8 months ; p < 0.001 ) in the sorafenib arm . However , sorafenib was not able to increase the time to symptomatic progression . In terms of toxicity , there were more cases of diarrhea , weight loss , h and –foot skin reaction and hypophosphatemia among the patients receiving sorafenib , the majority of which were of grade 1 or 2 severity . The SHARP trial has demonstrated that sorafenib is effective in prolonging median survival and time-to-progression in patients with advanced HCC and that it is generally well tolerated with a manageable adverse events profile BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies BACKGROUND In Japan and South Korea , transarterial chemoembolisation ( TACE ) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma ( HCC ) . Sorafenib , a multikinase inhibitor , has been shown effective and safe in patients with advanced HCC . This phase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable HCC who responded to TACE . METHODS Patients ( n=458 ) with unresectable HCC , Child-Pugh class A cirrhosis and ≥25 % tumour necrosis/shrinkage 1 - 3 months after 1 or 2 TACE sessions were r and omised 1:1 to sorafenib 400 mg bid or placebo and treated until progression/recurrence or unacceptable toxicity . Primary end-point was time to progression/recurrence ( TTP ) . Secondary end-point was overall survival ( OS ) . FINDINGS Baseline characteristics in the two groups were similar ; > 50 % of patients started sorafenib>9 weeks after TACE . Median TTP in the sorafenib and placebo groups was 5.4 and 3.7 months , respectively ( hazard ratio ( HR ) , 0.87 ; 95 % confidence interval ( CI ) , 0.70 - 1.09 ; P=0.252 ) . HR ( sorafenib/placebo ) for OS was 1.06 ( 95 % CI , 0.69 - 1.64 ; P=0.790 ) . Median daily dose of sorafenib was 386 mg , with 73 % of patients having dose reductions and 91 % having dose interruptions . Median administration of sorafenib and placebo was 17.1 and 20.1 weeks , respectively . No unexpected adverse events were observed . INTERPRETATION This trial , conducted prior to the reporting of registration al phase III trials , found that sorafenib did not significantly prolong TTP in patients who responded to TACE . This may have been due to delays in starting sorafenib after TACE and /or low daily sorafenib doses Background Disease progression of hepatocellular cancer ( HCC ) in patients eligible for liver transplantation ( LTx ) occurs in up to 50 % of patients , result ing in withdrawal from the LTx waiting list . Transarterial chemoembolization ( TACE ) is used as bridging therapy with highly variable response rates . The oral multikinase inhibitor sorafenib significantly increases overall survival and time-to-progression in patients with advanced hepatocellular cancer . Design The HeiLivCa study is a double-blinded , controlled , prospect i ve , r and omized multi-centre phase III trial . Patients in study arm A will be treated with transarterial chemoembolization plus sorafenib 400 mg bid . Patients in study arm B will be treated with transarterial chemoembolization plus placebo . A total of 208 patients with histologically confirmed hepatocellular carcinoma or HCC diagnosed according to EASL criteria will be enrolled . An interim patients ' analysis will be performed after 60 events . Evaluation of time-to-progression as primary endpoint ( TTP ) will be performed at 120 events . Secondary endpoints are number of patients reaching LTx , disease control rates , OS , progression free survival , quality of live , toxicity and safety . Discussion As TACE is the most widely used primary treatment of HCC before LTx and sorafenib is the only proven effective systemic treatment for advanced HCC there is a strong rational to combine both treatment modalities . This study is design ed to reveal potential superiority of the combined TACE plus sorafenib treatment over TACE alone and explore a new neo-adjuvant treatment concept in HCC before LTx LBA154^ Background : The global SPACE trial was conducted to evaluate the efficacy and safety of S in combination with TACE with DEBDOX in patients ( pts ) with intermediate-stage HCC ( BCLC B ) . METHODS Pts were eligible if they had asymptomatic , unresectable , multinodular tumors without vascular invasion ( VI ) or extrahepatic spread ( EHS ) ; Child-Pugh A liver functional status ; and ECOG PS 0 . Pts were r and omized to receive S 400 mg bid or matching P continuously ( 1 cycle = 4 wks ) until progression . All pts received TACE with DEBDOX ( 150 mg doxorubicin ; Biocompatibles UK Ltd ) 3 - 7d after first dose of study drug , and then on d1 ( ±4d ) of months 3 , 7 , and 13 , and q6 months thereafter . The primary endpoint was time to radiologic progression ( TTP ) by independent review ( predefined alpha = 0.15 ) . Secondary endpoints were overall survival ( OS ) , time to VI/EHS , time to untreatable progression ( TTUP ) , and safety . RESULTS Of 452 pts screened , 307 were r and omized to S ( n=154 ) or P ( n=153 ) . The HR for TTP was 0.797 ( Output:	Conclusion Combination of sorafenib and TACE showed survival and clinical benefits in patients with HCC , though enhanced morbidity
MS21607	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES To examine how the availability of fetal fibronectin testing affects the utilization of hospital re sources . METHODS A comparison of the rates , duration , and costs of hospitalization for a prospect i ve cohort of women who presented with preterm labour after fetal fibronectin ( Ffn ) testing became available , and a historical baseline cohort who presented with preterm labour before fetal fibronectin testing was available . The study included singleton pregnancies presenting between 24 and 34 weeks ' gestation with signs and symptoms of preterm labour . The women in each study cohort presented during a design ated 20-week period . RESULTS We examined the records of 116 subjects with comparable gestational age distributions in each 20-week period . During the study period when Ffn testing was available , 51 tests were performed . Four tests were invalid , and 12 subjects who were tested did not meeting the inclusion criteria . Admissions for preterm labour in the study period were significantly less than in the baseline cohort ( 12.1 % vs. 24.1 % , P = 0.03 ) , with no difference in preterm births ( 8.6 % vs. 7.8 % ) . The mean length of stay per patient with preterm labour declined from 5.2 days to 0.6 days ( P < 0.0001 ) , and the mean cost per patient with preterm labour declined from $ 3666 to $ 581 ( P < 0.0001 ) . In the 20-week study period , there was a reduction in total length of hospital stay from 145 to 28 days , with an overall reduction in total cost from $ 102 660 to $ 26 169 . CONCLUSION The availability of Ffn testing was associated with a reduction in hospital admissions , length of hospital stay , and overall hospital costs in the management of threatened preterm labour OBJECTIVE : To assess the impact of activity restriction ( AR ) on the incidence of preterm birth in women treated for preterm labor testing negative for fetal fibronectin ( fFN ) . STUDY DESIGN : Women who were diagnosed with preterm labor and tocolyzed with magnesium sulfate were concurrently screened with fFN for the purpose of subsequent management . Included were consenting patients with negative fFN , gestational age 23 0/7–33 6/7 weeks , cervical dilation ≤3 cm , and minimal vaginal bleeding . Patients were r and omized to AR or no AR . Primary study outcome was incidence of preterm delivery and interval from r and omization to delivery . RESULTS : A total of 73 women with negative fFN were r and omized ( 36 with AR , 37 without AR ) . The overall preterm birth rate was 40 % , with 44.4 % of patients with AR and 35.1 % of patients without AR delivering preterm , p=0.478 . CONCLUSION : Maternal AR did not impact pregnancy outcome . The incidence of preterm birth in symptomatic women testing fFN negative was higher than previously reported This week , a series of four articles considers the place of the r and omised controlled trial as we approach the second century of experience with the concept . Its basic principle is genuine uncertainty as to which treatment arm of the trial it would be in a patient 's best interests to enter . This is not necessarily an easy concept to transmit , OBJECTIVE We sought to investigate if determination of cervicovaginal interleukin-6 ( IL-6 ) levels would enhance the positive predictive value of fetal fibronectin ( fFN ) for preterm birth . METHODS A prospect i ve cohort study was undertaken of 135 women between 24 and 34 weeks gestation with symptoms of suspected preterm labor . Cervicovaginal secretions were collected for both IL-6 and fFN and measured by immunoassay and ELISA , respectively . Outcome variables included preterm delivery in less than 48 h , within 7 days , and prior to 37 weeks . Statistical analysis was performed with Fisher 's exact test , regression for logarithmic transform levels , and multivariate logistic regression . ROC curves were created for IL-6 levels . RESULTS IL-6 and fFN levels were both elevated in cervicovaginal secretions of women with symptoms of preterm labor . IL-6 values > 100 pg/ml result ed in a odds ratio for delivery at < 37 weeks of 1.57 ( 95%CI=0.89 - 2.75 , P=.11 ) , whereas fFN values > 50 ng/ml result ed in a preterm delivery risk of 4.58 ( 95%CI=1.54 - 13.35 , P=.003 ) . Combining IL-6 and fFN results did not improve upon the predictive value of fFN alone for preterm birth [ odds ratio 4.00 ( 95%CI=1.31 - 12.17 , P=.015 ) ] . CONCLUSION Cervicovaginal IL-6 levels did not provide any additional , independent effect on the prediction of preterm birth beyond that of fFN testing alone Aims The purpose of this pilot study was to determine the role of foetal fibronectin ( fFN ) testing in women presenting to hospital with symptoms of preterm labour in reducing the hospital admissions , without significantly increasing the risk of preterm birth and neonatal respiratory distress syndrome . Methods Women with symptoms of preterm labour were assigned r and omly to receive fFN ( n = 44 ) or to preterm labour management without fFN ( n = 44 ) . In the testing arm , the result of the test was revealed to the clinician . Clinical outcomes were compared in the two groups . The time period covered by the r and omised controlled trial ( RCT ) was from December 2007 to March 2009 . The RCT was conducted in two large maternity units in the west of Scotl and , one in Glasgow the other in Ayrshire . Results All the women with fibronectin positive got admitted while only 32.4 % of the fibronectin negatives were admitted ( P = 0.002 ) . There was a significant difference in the mean length of stay between the fibronectin positives which was 47.17 h , and the negatives which was 12.9 h ( P = 0.018 ) . Overall the control and testing arms did not differ in respect to admissions and length of stay . 5 out of 7 positives and 11 out of 37 negatives had corticosteroids ( P = 0.089 ) . 2 out of 7 positives and 1 out of 37 negatives had tocolytics ( P = 0.073 ) . Conclusions Those who had the fFN test done were less likely to be admitted in the hospital and had a shorter length of stay , without any increase in the adverse maternal or foetal effects , avoiding unnecessary admissions OBJECTIVE To assess the clinical value of cervicovaginal fetal fibronectin ( FFN ) in the prediction of preterm delivery ( PTD ) in women with signs and symptoms of preterm labor ( PTL ) . METHOD This investigation prospect ively studied a cohort of a women with symptoms of PTL , between 24 and 37 weeks ' gestation with < 3 cm of cervical dilatation and intact membranes . Cases were evaluated in terms of maternal demographic characteristics like age , body mass index , number of parities , previous PTL history , Bishop scores at admission , gestational age at delivery , mode of delivery , use of tocolytic or steroids , presence of histologic chorioamnionitis , neonatal outcomes and delivery before 34 weeks ' gestation as well as within seven days of admission . RESULTS A total number of 68 cases were included in the study . There were no statistically significant differences between positive and negative FFN groups in terms of maternal characteristics , mode of delivery and adverse neonatal outcomes . However , FFN + cases had higher Bishop scores on admission ( 3.4 + /- 1.2 vs 2.5 + /- 0.3 , p = 0.03 ) and lower gestational age at delivery ( 33.4 + /- 3.1 weeks vs 36.8 + /- 2.1 weeks , p = 0.002 ) . Likelihood ratio ( LR ) for positive results was 1.83 ( 95 % CI : 1.61 - 2.26 ) for predicting birth before 34 weeks ' gestation , with a corresponding negative LR of 0.62 ( 95 % CI : 0.3 - 1.2 ) . LR for positive results was 4.34 ( 95 % CI : 3.65 - 5.12 ) for predicting birth within seven days of testing , with a corresponding negative LR of 0.3 ( 95 % CI : 0.2 - 0.5 ) . CONCLUSION Based on the results of cervicovaginal FFN , positive tests represent an increased likelihood of PTD among women with symptoms of threatened preterm labor OBJECTIVE The purpose of this study was to codify the relationship between bacterial vaginosis/fetal fibronectin and preterm labor/birth . STUDY DESIGN In this prospect i ve study , 185 women who were symptomatic for preterm labor were assessed for bacterial vaginosis and fetal fibronectin . RESULTS These women comprised 4 groups : group A ( n=23 women ; + bacterial vaginosis/+fetal fibronectin ) ; group B ( n=31 women ; -bacterial vaginosis/+fetal fibronectin ) ; group C ( n=47 women ; + bacterial vaginosis/-fetal fibronectin ) ; and group D ( n=84 women ; -bacterial vaginosis/-fetal fibronectin ) . The time interval from gestational age at testing until delivery was significantly shorter for groups A and B versus groups C and D ( P < or = .05 and P < .001 , respectively ) . Similarly , delivery at < 32 weeks of gestation was increased in group B ( 26 % ) compared with groups A ( 9 % ) , C ( 2 % ) , and D ( 5 % ; P < .009 ; odds ratio , 165.90 ; 95 % CI , 30.02 , 916.08 ) . CONCLUSION Women who are symptomatic for preterm labor should be considered for fetal fibronectin and bacterial vaginosis testing OBJECTIVE Our purpose was to determine whether tumor necrosis factor-alpha , interleukin-6 , and fetal fibronectin could be identified in the lower genital tract during pregnancy and whether their occurrence was associated with preterm delivery . STUDY DESIGN A prospect i ve cohort study was undertaken of 111 pregnant women in which cervicovaginal swabs were obtained at < 37 weeks ' gestation . Seventy-three specimens were obtained from women during routine prenatal examination , whereas 38 specimens were obtained from women undergoing evaluation of preterm labor . Interleukin-6 and fetal fibronectin levels were determined by enzyme-linked immunosorbent assays , whereas tumor necrosis factor-alpha determinations were by bioassay . Urinary tract and lower genital tract sample s were cultured for evidence of infection . The rates of maternal and neonatal complications were assessed . RESULTS In patients undergoing evaluation for preterm labor the presence of tumor necrosis factor-alpha or fetal fibronectin was associated with an increased prevalence of preterm delivery . Women with tumor necrosis factor-alpha had a 6.19 greater risk ( p < 0.005 ) , whereas the presence of fetal fibronectin was associated with a 4.81 greater risk ( p < 0.05 ) , of preterm birth . This association was not evident in women who were sample d during routine prenatal examinations . In all women the presence of cytokines in the lower genital tract correlated with detection of fetal fibronectin . CONCLUSION Localized inflammatory responses may lead to microscopic disruption in the amniotic membranes , leading to leakage of fibronectin . In patients being evaluated for preterm labor , the presence of tumor necrosis factor-alpha or fetal fibronectin in the lower genital tract is predictive of subsequent preterm delivery Objective To assess the accuracy of vaginal fetal fibronectin ( FFN ) as a screening test for preterm delivery in a community hospital . Study design A prospect i ve cohort of patients at high risk for preterm delivery at a community hospital underwent testing with FFN over a 15 month-period ( March 2004–May 2005 ) . Indications for testing were preterm labor , multiple pregnancies , cervical shortening , and cerclage . Pregnancy characteristics were retrieved on all women with positive FFN results and controls in a 1:2 ratio . Outcome variables included interval to delivery ; length of hospital stay ; and rates of preterm delivery < 37 weeks . In the presence of serial FFN testing , only the initial result was used for calculation of diagnostic indices . Statistical analysis utilized t-test , Fisher ’s exact test and logistic regression analyis to control for gestational age at testing , with P < 0.05 or odds ratio ( OR ) with 95 % confidence interval ( CI ) not inclusive of the unity considered significant . Results Two hundred and fifty seven FFN tests were performed in 230 women , of which 33 ( 14.3 % ) had positive FFN results . Duration of hospital stay was significantly shorter for patients with negative than positive results ( 8 h vs. 2.1 days , P = 0.011 ) . Women with positive FFN were more likely to deliver within 14 days ( OR = 6.5 , 95 % CI 1.4 ; 30.7 ) , within 21 days ( OR = 4.8 ; 95 % CI 1.4 ; 16.6 ) , before 34 weeks ( OR = 5.0 , 95 % CI 1.7 ; 14.8 ) and before 37 weeks ( OR = 3.1 ; 95 % CI Output:	Sensitivity analyses indicated that admission rate had the largest impact on results . CONCLUSIONS Fetal fibronectin testing has moderate accuracy for predicting PTB . The main potential role is likely to be reducing health-care re source usage by identifying women not requiring intervention . Evidence from RCTs suggests that fFN does not increase adverse outcomes and may reduce re source use . The base-case analysis showed a modest cost difference in favour of fFN testing , which is largely dependent on whether or not fFN testing reduces hospital admission .
MS21608	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES Despite studies that show improvements in both st and ards of care and outcomes with the judicious application of clinical practice guidelines ( CPGs ) , their clinical utilization remains low . This r and omized controlled trial examined the use of a wirelessly networked mobile computer ( MC ) by physicians at the bedside with access to an emergency department information system , decision support tools ( DSTs ) , and other software options . METHODS Each of ten volunteer emergency physicians was r and omized using a matched-pair design to work five shifts in st and ard fashion ( desktop computer [ DC ] access ) and five shifts with a wirelessly networked MC . Work pattern issues and electronic CPG/DST use were compared using end-of-shift satisfaction question naires and review of a CPG/DST data base . Repeated- measures analysis of variance was used to examine between-shift differences . RESULTS A total of 100 eight-hour shifts were evaluated ; 99 % compliance with postshift question naires was achieved . Using a seven-point Likert scale ( MC values first ) , MCs were rated as being as fast ( 5.04 vs. 4.54 ; p=0.13 ) and convenient ( 5.08 vs. 4.14 ; p=0.07 ) as DCs . Overall , physicians rated MCs to be less efficient ( 3.18 vs. 4.30 ; p=0.02 ) but encouraged more frequent use of DSTs ( 4.10 vs. 3.47 ; p=0.03 ) without impacting doctor-patient communication ( 2.78 vs. 2.96 ; p=0.51 ) . During the study period , physician use of an intranet Web application ( eCPG ) was more frequent during shifts assigned to the MC when compared with the DC ( eCPG uses/shift , 3.6 vs. 2.0 ; p=0.033 ) . CONCLUSIONS The MC technology permitted physicians to access information at the bedside and increased the use of CPG/DST tools . According to physicians , patients appeared to accept their use of information technology to assist in decision making . Development of improved computer technology may address the major limitation of MC portability OBJECTIVE : To determine the effectiveness of a quality improvement program to improve pediatricians ' adherence to existing , evidence -based , attention-deficit/hyperactivity disorder ( ADHD ) practice guidelines . METHODS : Forty-nine community-based pediatricians at 8 practice s participated in a cluster-r and omized trial . Practice s were matched according to the numbers of pediatricians and the proportions of patients receiving Medicaid . The medical charts for a r and om sample of patients with ADHD for each of the participating pediatricians were examined at baseline and 6 months . All practice s participated in 4 sessions of training , including didactic lectures and office flow modification workshops . Practice s were then given access to an ADHD Internet portal that allowed parents , teachers , and pediatricians to input information ( eg , rating scales ) about patients , after which information was scored , interpreted , and formatted in a report style that was helpful for assessment and treatment of patients with ADHD . Physicians evaluated their practice behaviors quarterly and addressed underperforming areas . RESULTS : Pediatricians in the intervention group , compared with those in the control group , demonstrated significantly higher rates of many American Academy of Pediatrics – recommended ADHD care practice s , including collection of parent ( Cohen 's d = 0.69 ) and teacher ( d = 0.68 ) rating scales for assessment of children with ADHD , use of Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria ( d = 0.85 ) , and use of teacher rating scales to monitor treatment responses ( d = 1.01 ) . CONCLUSION : A quality improvement intervention that can be widely disseminated by using Internet-based information technology significantly improved the quality of ADHD care in community-based pediatric setting Background Research to assess the effect of interventions to improve the processes of shared decision making and self-management directed at health care professionals is limited . Using the protocol of Intervention Mapping , a Web-based intervention directed at health care professionals was developed to complement and optimize health services in patient-centered care . Objective The objective of the Web-based intervention was to increase health care professionals ’ intention and encouraging behavior toward patient self-management , following cardiovascular risk management guidelines . Methods A r and omized controlled trial was used to assess the effect of a theory-based intervention , using a pre-test and post-test design . The intervention website consisted of a module to help improve professionals ’ behavior , a module to increase patients ’ intention and risk-reduction behavior toward cardiovascular risk , and a parallel module with a support system for the health care professionals . Health care professionals ( n=69 ) were recruited online and r and omly allocated to the intervention group ( n=26 ) or ( waiting list ) control group ( n=43 ) , and invited their patients to participate . The outcome was improved professional behavior toward health education , and was self-assessed through question naires based on the Theory of Planned Behavior . Social-cognitive determinants , intention and behavior were measured pre-intervention and at 1-year follow-up . Results The module to improve professionals ’ behavior was used by 45 % ( 19/42 ) of the health care professionals in the intervention group . The module to support the health professional in encouraging behavior toward patients was used by 48 % ( 20/42 ) . The module to improve patients ’ risk-reduction behavior was provided to 44 % ( 24/54 ) of patients . In 1 of every 5 patients , the guideline for cardiovascular risk management was used . The Web-based intervention was poorly used . In the intervention group , no differences in social-cognitive determinants , intention and behavior were found for health care professionals , compared with the control group . We narrowed the intervention group and no significant differences were found in intention and behavior , except for barriers . Results showed a significant overall difference in barriers between the intervention and the control group ( F 1=4.128 , P=.02 ) . Conclusions The intervention was used by less than half of the participants and did not improve health care professionals ’ and patients ’ cardiovascular risk-reduction behavior . The website was not used intensively because of time and organizational constraints . Professionals in the intervention group experienced higher levels of barriers to encouraging patients , than professionals in the control group . No improvements were detected in the processes of shared decision making and patient self-management . Although participant education level was relatively high and the intervention was pre-tested , it is possible that the way the information was presented could be the reason for low participation and high dropout . Further research embedded in professionals ’ regular consultations with patients is required with specific emphasis on the processes of dissemination and implementation of innovations in patient-centered care . Trial Registration Netherl and s Trial Register Number ( NTR ) : NTR2584 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=2584 ( Archived by WebCite at http://www.webcitation.org/6STirC66r ) CONTEXT Despite evidence that a variety of continuing medical education ( CME ) techniques can foster physician behavioral change , there have been no r and omized trials comparing performance outcomes for physicians participating in Internet-based CME with physicians participating in a live CME intervention using approaches documented to be effective . OBJECTIVE To determine if Internet-based CME can produce changes comparable to those produced via live , small-group , interactive CME with respect to physician knowledge and behaviors that have an impact on patient care . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted from August 2001 to July 2002 . Participants were 97 primary care physicians drawn from 21 practice sites in Houston , Tex , including 7 community health centers and 14 private group practice s. A control group of 18 physicians from these same sites received no intervention . INTERVENTIONS Physicians were r and omly assigned to an Internet-based CME intervention that could be completed in multiple sessions over 2 weeks , or to a single live , small-group , interactive CME workshop . Both incorporated similar multifaceted instructional approaches demonstrated to be effective in live setting s. Content was based on the National Institutes of Health National Cholesterol Education Program -- Adult Treatment Panel III guidelines . MAIN OUTCOME MEASURES Knowledge was assessed immediately before the intervention , immediately after the intervention , and 12 weeks later . The percentage of high-risk patients who had appropriate lipid panel screening and pharmacotherapeutic treatment according to guidelines was documented with chart audits conducted over a 5-month period before intervention and a 5-month period after intervention . RESULTS Both interventions produced similar and significant immediate and 12-week knowledge gains , representing large increases in percentage of items correct ( pretest to posttest : 31.0 % [ 95 % confidence interval { CI } , 27.0%-35.0 % ] ; pretest to 12 weeks : 36.4 % [ 95 % CI , 32.2%-40.6 % ] ; P<.001 for all comparisons ) . Chart audits revealed high baseline screening rates in all study groups ( > or = 93 % ) with no significant postintervention change . However , the Internet-based intervention was associated with a significant increase in the percentage of high-risk patients treated with pharmacotherapeutics according to guidelines ( preintervention , 85.3 % ; postintervention , 90.3 % ; P = .04 ) . CONCLUSIONS Appropriately design ed , evidence -based online CME can produce objective ly measured changes in behavior as well as sustained gains in knowledge that are comparable or superior to those realized from effective live activities The purpose of this r and omized , controlled , home care intervention was to test the effectiveness of two nurse-targeted , e-mail-based interventions to increase home care nurses ' adherence to pain assessment and management guidelines , and to improve patient outcomes . Nurses from a large urban non-profit home care organization were assigned to usual care or one of two interventions upon identification of an eligible cancer patient with pain . The basic intervention consisted of a patient-specific , one-time e-mail reminder highlighting six pain-specific clinical recommendations . The augmented intervention supplemented the initial e-mail reminder with provider prompts , patient education material , and clinical nurse specialist outreach . Over 300 nurses were r and omized and outcomes of 673 of their patients were review ed . Data collection involved clinical record abstract ion of nurse care practice s and patient interviews completed approximately 45 days after start of care . The intervention had limited effect on nurse-documented care practice s but patient outcomes were positively influenced . Patients in the augmented group improved significantly over the control group in ratings of pain intensity at its worst , whereas patients in the basic group had better ratings of pain intensity on average . Other outcomes measures were also positively influenced but did not reach statistical significance . Our findings suggest that although reminders have some role in improving cancer pain management , a more intensive approach is needed for a generalized nursing workforce with limited recent exposure to state-of-the-art pain management practice OBJECTIVE To investigate the effectiveness of an Inpatient Diabetes Management Program ( IDMP ) on physician knowledge and inpatient glycemic control . METHODS Residents assigned to General Internal Medicine inpatient services were r and omized to receive the IDMP ( IDMP group ) or usual education only ( non-IDMP group ) . Both groups received an overview of inpatient diabetes management in conjunction with reminders of existing order sets on the hospital Web site . The IDMP group received print copies of the program and access to an electronic version for a personal digital assistant ( PDA ) . A Diabetes Knowledge Test ( DKT ) was administered at baseline and at the end of the 1-month rotation . The frequency of hyperglycemia among patients under surveillance by each group was compared by using capillary blood glucose values and a dispersion index of glycemic variability . IDMP users completed a question naire related to the program . RESULTS Twenty-two residents participated ( 11 in the IDMP group and 11 in the non-IDMP group ) . Overall Diabetes Knowledge Test scores improved in both groups ( IDMP : 69 % ± 1.7 % versus 83 % ± 2.1 % , P = .003 ; non-IDMP : 76 % ± 1.2 % versus 84 % ± 1.4 % , P = .02 ) . The percentage of correct responses for management of corticosteroid-associated hyperglycemia ( P = .004 ) and preoperative glycemic management ( P = .006 ) improved in only the IDMP group . The frequency of hyperglycemia ( blood glucose level > 180 mg/dL ) and the dispersion index ( 5.3 ± 7.6 versus 3.7 ± 5.6 ; P = .2 ) were similar between the 2 groups . CONCLUSION An IDMP was effective at improving physician knowledge for managing hyperglycemia in hospitalized patients treated with corticosteroids or in preparation for surgical procedures . Educational programs directed at improving overall health care provider knowledge for inpatient glycemic management may be beneficial ; however , improvements in knowledge do not necessarily result in improved glycemic outcomes Background Clinical practice guidelines are important for transmitting research findings into practice and facilitating the application of evidence -based practice ( EBP ) . There is a paucity of knowledge about the impact of guideline implementation strategies in primary care physical therapy . The aim of this study was to evaluate the effect of a guideline implementation intervention in primary care physical therapy in western Sweden . Methods An implementation strategy based on theory and current evidence was developed . A tailored , multi-component implementation intervention , addressing earlier identified determinants , was carried out in three areas comprising 28 physical therapy practice s including 277 physical therapists ( PTs ) ( intervention group ) . In two adjacent areas , 171 PTs at 32 practice s received no intervention ( control group ) . The core component of the intervention was an implementation seminar with group discussion s. Among other components were a website and email rem Output:	Results Website studies demonstrated significant improvements in perceived usefulness and perceived ease of use , but not for knowledge , reducing barriers , and intention to use clinical practice guidelines . Computer software studies demonstrated significant improvements in perceived usefulness , but not for knowledge and skills . Web-based workshop and email studies demonstrated significant improvements in knowledge , perceived usefulness , and skills . An electronic educational game intervention demonstrated a significant improvement from baseline in knowledge after 12 and 24 weeks . Computerized decision support system studies demonstrated variable findings for improvement in skills . Multifaceted interventions demonstrated significant improvements in beliefs about capabilities , perceived usefulness , and intention to use clinical practice guidelines , but variable findings for improvements in skills . Most multifaceted studies demonstrated significant improvements in knowledge . Conclusions The findings suggest that health professionals ’ perceived usability and practice behavior change vary by type of information and communication technology . Heterogeneity and the paucity of properly conducted studies did not allow for a clear comparison between studies and a conclusion on the effectiveness of information and communication technologies as a knowledge translation strategy for the dissemination of clinical practice guidelines
MS21609	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Catheter-restricted antibiotic lock solutions were found to be effective in the prevention of catheter-related bacteremia ( CRB ) , but insufficient data are available about the ideal agent and dose . We hypothesized that a low concentration of gentamicin would be as effective as the high doses studied in the past . METHODS In this prospect i ve , open-labeled , r and omized , clinical trial of patients on long-term hemodialysis therapy , patients were r and omly assigned to administration of an antibiotic lock solution of gentamicin/citrate ( 4 mg/mL ) , minocycline/EDTA , or the control solution of heparin . Patients were followed up until the study end point of CRB was reached or a censoring event occurred . Interim data analysis was performed after 6 months to assess data safety ; efficacy was noted and the study was terminated early . RESULTS Sixty-two patients were enrolled into the study , evenly distributed in 3 arms , with data from 1 patient excluded from analysis . Seven of 20 patients in the heparin group ( 4.0 events/1,000 catheter days ) , 1 of 21 patients in the minocycline group ( 0.4 events/1,000 catheter days ) , and none of 20 patients in the gentamicin group developed bacteremia . Results were statistically significant by using 2-tailed Fisher exact test ; heparin versus gentamicin , P = 0.008 , and heparin versus minocycline , P = 0.020 . CONCLUSION Antibiotic lock solutions are superior to the st and ard heparin lock alone in the prevention of CRBs , and low-dose gentamicin solution has efficacy similar to that of greater concentrations used in previous studies INTRODUCTION Catheter-related infection is associated with increased all-cause mortality and morbidity in hemodialysis patients . This study aim ed to evaluate an antimicrobial lock solution ( cloxacillin and heparin ) in temporary noncuffed double-lumen catheters for long-term intermittent hemodialysis as a method of preventing catheter-related infection . MATERIAL S AND METHODS Patients on hemodialysis with noncuffed temporary double lumen catheter were r and omly divided into 2 groups . Fifty patients received a solution containing cloxacillin , 100 mg/mL , plus heparin , 1000 IU/mL as a 2.5-mL solution instilled in each of catheter lumens after dialysis session . Another 50 patients received only heparin . They were allowed to dwell until the next session of dialysis . RESULTS One catheter-related bacteremia was observed in the antibiotic group whereas catheter-related bacteremia was observed in 8 of those who received heparin only . The rate of catheter-related bacteremia episodes were 0.5 per 1000 catheter-days in the antibiotic group versus 7.8 per 1000 catheter-days in the control group ( P = .02 ) . CONCLUSIONS In the present study , application of cloxacillin as antibiotic lock solution for dialysis catheters result ed in a considerable reduction in catheter-related bacteremia rate BACKGROUND AND OBJECTIVES Citrate 4 % has antithrombotic and antibacterial properties , which makes it a potentially superior alternative to heparin as an indwelling intraluminal locking agent . DESIGN , SETTING , PARTICIPANTS , AND MEASUREMENTS Sixty-one prevalent hemodialysis ( HD ) patients dialyzing with a tunneled cuffed HD catheter were r and omized in a pilot study to receive either heparin 5000 U/ml or citrate 4 % as a locking agent after HD . The primary outcomes were the development of catheter dysfunction ( defined as a blood pump speed < 250 ml/min or the use of tissue plasminogen activator ) and catheter-associated bacteremia . The secondary outcomes were the development of an exit-site infection or bleeding complications ( either local or systemic ) . RESULTS Citrate had comparable catheter dysfunction episodes to heparin ( 13/32 [ 41 % ] cases versus 12/29 [ 41 % ] cases , respectively ) . There were no differences in the development of catheter-associated bacteremia ( 2.2/1000 catheter days citrate versus 3.3/1000 catheter days heparin group ; P = 0.607 ) or exit-site infection ( 2.2/1000 catheter days for both groups ) . CONCLUSIONS The preliminary findings from our pilot study demonstrate that 4 % citrate is effective in maintaining catheter patency and does not appear to have any increased incidence of infections . Because citrate is significantly cheaper and has a more favorable side effect profile than heparin , it can be considered a potentially better locking agent in HD catheters Background Catheter-related bacteraemias ( CRBs ) contribute significantly to morbidity , mortality and health care costs in dialysis population s. Despite international guidelines recommending avoidance of catheters for haemodialysis access , hospital admissions for CRBs have doubled in the last decade . The primary aim of the study is to determine whether weekly instillation of 70 % ethanol prevents CRBs compared with st and ard heparin saline . Methods / design The study will follow a prospect i ve , open-label , r and omized controlled design . Inclusion criteria are adult patients with incident or prevalent tunneled intravenous dialysis catheters on three times weekly haemodialysis , with no current evidence of catheter infection and no personal , cultural or religious objection to ethanol use , who are on adequate contraception and are able to give informed consent . Patients will be r and omized 1:1 to receive 3 mL of intravenous- grade 70 % ethanol into each lumen of the catheter once a week and st and ard heparin locks for other dialysis days , or to receive heparin locks only . The primary outcome measure will be time to the first episode of CRB , which will be defined using st and ard objective criteria . Secondary outcomes will include adverse reactions , incidence of CRB caused by different pathogens , time to infection-related catheter removal , time to exit site infections and costs . Prospect i ve power calculations indicate that the study will have 80 % statistical power to detect a clinical ly significant increase in median infection-free survival from 200 days to 400 days if 56 patients are recruited into each arm . Discussion This investigator-initiated study has been design ed to provide evidence to help nephrologists reduce the incidence of CRBs in haemodialysis patients with tunnelled intravenous catheters . Trial Registration Australian New Zeal and Clinical Trials Registry Number : As a result of the high rate of infection , the NKF-K/DOQI guidelines recommended that an uncuffed catheter ( UC ) should not be used for longer than three weeks . However , the findings of the Dialysis Outcomes and Practice Patterns Study recognized that 48 % of new hemodialysis patients in the US and 75 % in Europe used UC for temporary access during arteriovenous fistula or graft maturation . The antibiotic lock technique ( ALT ) has been recommended to prevent catheter-related bacteremia ( CRB ) . Here , we prospect ively evaluated the efficacy of catheter-restricted filling using an antibiotic lock solution in preventing CRB . A total of 120 new hemodialysis patients requiring a temporary catheter while waiting for placement and maturation of an arteriovenous fistula or graft were enrolled in this study . Patients with a UC were r and omly assigned to receive either an antibiotic-heparin lock solution ( antibiotic group : cefazolin 10 mg/ml , gentamicin 5 mg/ml , heparin 1000 U/ml ) or a heparin lock solution ( no-antibiotic group : heparin 1000 U/ml ) as a catheter lock solution during the interdialytic period . The end point of the trial was CRB . CRB developed in seven ( 11.7 % ) patients in the no-antibiotic group ( Staphylococcus aureus , two ; Staphylococcus epidermidis , five ) whereas only one patient in the antibiotic group had S. aureus bacteremia . CRB rates per 1000 catheter-days were 0.44 in the antibiotic group versus 3.12 in the no-antibiotic group ( P=0.031 ) . Kaplan-Meier analysis also showed that mean CRB-free catheter survival of 59 days ( 95 % CI , 58 - 61 days ) in the antibiotic group was greater than that in the no-antibiotic group ( 55 days ; 95 % CI , 50 - 59 days ) . The results suggest that ALT may be a beneficial means of reducing the CRB rate in hemodialysis patients with UC Tunneled cuffed central vein catheters ( TCC ) are widely used for delivering hemodialysis ( HD ) . Infection is the principal cause of morbidity and mortality associated with central vein catheters in patients on HD . The optimal strategy to combat TCC infection is controversial . This prospect i ve study assesses the efficacy of antibiotic-lock therapy using vancomycin and gentamycin in preventing catheter-related blood stream bacterial infection in patients on HD . A total of 86 TCC in 69 HD patients were enrolled at the time of catheter insertion for delivering HD . Patients were r and omized into two groups : Group I ( 36 patients -39 insertions ) included TCC with antibiotic-lock therapy and Group II ( 33 patients -47 insertions ) with routine TCC management . Infection-free catheter survival of both groups was evaluated and compared at the end of the 18-month study period . A total of 72 TCC infections were detected with an incidence rate of 6.78 infections/1000 dialysis sessions . The rate of infection was significantly lower in Group I ( 4.39/1000 dialysis sessions ) compared to Group II ( 11.69/1000 dialysis sessions ) , p<0.001 . The bacteremia rate , as well as rate of clinical sepsis were also significantly lower in Group I than in Group II ( p<0.001 ) . There was no statistically significant difference in the rate of access site infection in the two groups ( p>0.05 ) . Our study suggests that antibiotic-lock therapy using a combination of vancomycin and gentamycin is useful in preventing catheter-related blood stream infection in patients on HD BACKGROUND Formation of an intraluminal microbial biofilm is noted to play a significant role in the development of catheter-related infections ( CRIs ) . Recently , it has been demonstrated that trisodium citrate ( TSC ) has superior antimicrobial effects over heparin for catheter locking . In this r and omized controlled trial , we compared the influence of catheter locking with heparin and TSC on the in vivo intraluminal biofilm formation in haemodialysis catheters . METHODS Six patients were studied from the time of catheter insertion for haemodialysis treatment . They were r and omly assigned to TSC 30 % or heparin 5000 U/ml for catheter locking for the duration of 1 month . After elective guidewire exchange of the catheter , the locking solution was also changed . After removal , catheters were dissected in three segments and examined by st and ardized scanning electron microscopy ( SEM ) to assess quantitative biofilm formation . Furthermore , st and ardized cultures of all segments were performed to identify any microorganisms . RESULTS In catheters filled with TSC , the average coverage by biofilm was 16 % versus 63 % in the heparin group ( P < 0.001 ) . A total of eight subsegments were associated with local catheter infection in the patients who were r and omized to heparin locking versus three subsegments who were assigned to TSC ( P < 0.05 ) . CONCLUSIONS Our study demonstrates that using TSC 30 % for catheter locking reduces the formation of microbial biofilm in haemodialysis catheters and culture-positive colonization . It is likely that this is the explanation for the observed prevention of CRIs by TSC locking Background and Purpose : Catheter-related bloodstream infection is the greatest threat to the safety of patients on hemodialysis . Catheter lock solutions containing heparin have been linked to an increased risk of hemorrhage and thrombocytopenia . Objectives : To ascertain the safety and efficacy for prevention of catheter-related bloodstream infection and catheter loss from patency failure of a novel catheter lock solution with antimicrobial and antithrombotic activity containing 0.24 M ( 7.0 % ) sodium citrate , 0.15 % methylene blue , 0.15 % methylparaben , and 0.015 % propylparaben ( C-MB-P ) , compared with heparin . Design : Multicenter , prospect i ve , r and omized , open-label trial with patients studied for up to 6 months . An independent clinical evaluation committee assessing trial outcomes was blinded to patients ' treatment assignments . Setting : Twenty-five outpatient hemodialysis units . Patients : Patients with end-stage renal disease receiving maintenance hemodialysis through a percutaneous cuffed and tunneled internal jugular hemodialysis catheters . Interventions : Participants Output:	Antibiotic antimicrobial and combined ( antibiotic-non antibiotic ) lock solutions decreased the incidence of CRI compared to control lock solutions , whereas non-antibiotic lock solutions reduce CRI only for tunnelled CVC . The effect on thrombosis incidence is uncertain for all antimicrobial lock solutions .
MS21610	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: CONTEXT The survival benefit of well-performed cardiopulmonary resuscitation ( CPR ) is well-documented , but little objective data exist regarding actual CPR quality during cardiac arrest . Recent studies have challenged the notion that CPR is uniformly performed according to established international guidelines . OBJECTIVES To measure multiple parameters of in-hospital CPR quality and to determine compliance with published American Heart Association and international guidelines . DESIGN AND SETTING A prospect i ve observational study of 67 patients who experienced in-hospital cardiac arrest at the University of Chicago Hospitals , Chicago , Ill , between December 11 , 2002 , and April 5 , 2004 . Using a monitor/defibrillator with novel additional sensing capabilities , the parameters of CPR quality including chest compression rate , compression depth , ventilation rate , and the fraction of arrest time without chest compressions ( no-flow fraction ) were recorded . MAIN OUTCOME MEASURE Adherence to American Heart Association and international CPR guidelines . RESULTS Analysis of the first 5 minutes of each resuscitation by 30-second segments revealed that chest compression rates were less than 90/min in 28.1 % of segments . Compression depth was too shallow ( defined as < 38 mm ) for 37.4 % of compressions . Ventilation rates were high , with 60.9 % of segments containing a rate of more than 20/min . Additionally , the mean ( SD ) no-flow fraction was 0.24 ( 0.18 ) . A 10-second pause each minute of arrest would yield a no-flow fraction of 0.17 . A total of 27 patients ( 40.3 % ) achieved return of spontaneous circulation and 7 ( 10.4 % ) were discharged from the hospital . CONCLUSIONS In this study of in-hospital cardiac arrest , the quality of multiple parameters of CPR was inconsistent and often did not meet published guideline recommendations , even when performed by well-trained hospital staff . The importance of high- quality CPR suggests the need for rescuer feedback and monitoring of CPR quality during resuscitation efforts Objective : To compare cardiopulmonary resuscitation ( CPR ) with a compression to ventilation ( C : V ) ratio of 15:2 vs. 30:2 , with and without use of an impedance threshold device ( ITD ) . Design : Prospect i ve r and omized animal and manikin study . Setting : Animal laboratory and emergency medical technician training facilities . Subjects : Twenty female pigs and 20 Basic Life Support (BLS)-certified rescuers . Interventions , Measurements , and Main Results : Animals : Acid-base status , cerebral , and cardiovascular hemodynamics were evaluated in 18 pigs in cardiac arrest r and omized to a C : V ratio of 15:2 or 30:2 . After 6 mins of cardiac arrest and 6 mins of CPR , an ITD was added . Compared to 15:2 , 30:2 significantly increased diastolic blood pressure ( 20 ± 1 to 26 ± 1 ; p < .01 ) ; coronary perfusion pressure ( 18 ± 1 to 25 ± 2 ; p = .04 ) ; cerebral perfusion pressure ( 16 ± 3 to 18 ± 3 ; p = .07 ) ; common carotid blood flow ( 48 ± 5 to 82 ± 5 mL/min ; p < .001 ) ; end-tidal CO2 ( 7.7 ± 0.9 to 15.7 ± 2.4 ; p < .0001 ) ; and mixed venous oxygen saturation ( 26 ± 5 to 36 ± 5 , p < .05 ) . Hemodynamics improved further with the ITD . Oxygenation and arterial pH were similar . Only one of nine pigs had return of spontaneous circulation with 15:2 , vs. six of nine with 30:2 ( p < 0.03 ) . Humans : Fatigue and quality of CPR performance were evaluated in 20 BLS-certified rescuers r and omized to perform CPR for 5 mins at 15:2 or 30:2 on a recording CPR manikin . There were no significant differences in the quality of CPR performance or measurement of fatigue . Significantly more compressions per minute were delivered with 30:2 in both the animal and human studies . Conclusions : These data strongly support the contention that a ratio of 30:2 is superior to 15:2 during manual CPR and that the ITD further enhances circulation with both C : V ratios OBJECTIVE Multiple procedures performed in parallel may cause each procedure to be performed less effectively than if performed in isolation . BLS performed by prehospital providers potentially includes artificial ventilations , chest compressions , and application of an automated external defibrillator ( AED ) . This study examines the effectiveness of artificial ventilation and chest compressions both with and without an AED . METHODS Thirty-six prehospital providers participated in a prospect i ve observational study . Tested in pairs ( n=18 ) , subjects r and omly completed three , 6-min scenarios [ apneic patient with a pulse ( VENT ) , a pulseless patient ( CPR ) , and a pulseless patient with an AED available ( CPR+AED ) ] . A full-torso manikin capable of generating a carotid pulse was connected to a computer to record number of ventilations , tidal volume , flow rate , number of compressions , and compression depth . Data were analyzed by t-test , ANOVA , and Mann-Whitney U-test . RESULTS Artificial ventilation performed in isolation provided more correct ventilations than during CPR or CPR+AED ( 25.7 % , 14.2 % , 13.7 % , p=0.02 ) . Fewer ventilations were delivered during CPR and CPR+AED ( p=0.03 ) . More compressions were delivered with CPR alone vs. CPR+AED ( 51.9 , 35.7 min(-1 ) , p=0.00 ) . More correct compressions were delivered during CPR alone vs. CPR+AED ( p=0.05 ) . CONCLUSIONS Both the quality and quantity of BLS decreases as the number of procedures performed simultaneously increases . Further decrements might occur when ALS skills enter into resuscitation . These results suggest a need to automate and /or prompt the performance of BLS to optimize resuscitation Objectives : To discover the circumstances of out of hospital cardiac death irrespective of resuscitation attempts . Design : Prospect i ve community study over the two years 1994 and 1995 . Setting : The health districts of Brighton , South Glamorgan , and York , UK . Subjects : 1290 victims of sudden death or cardiac arrest caused by coronary heart disease who were under 76 years of age . Interventions : Basic and advanced life support for witnessed cardiac arrests . Main outcome measures : Survival to reach hospital and for 30 days after the arrest . Results : 35 ( 35 % ) of 101 patients ( mean age 64 ) whose arrest was witnessed by a doctor or paramedic survived for 30 days compared with 9 of 464 ( 2 % ) whose arrest was witnessed by a relative or byst and er at home ( mean age 66 ) and 15 of 200 ( 8 % ) whose arrest was witnessed in a public place ( mean age 61 ) . None of the 525 victims of an unwitnessed arrest survived but the majority of those whose arrest was witnessed had complained of new symptoms before the arrest . Victims who were given basic life support by relatives or byst and ers had better survival ( 14 of 183 ( 8 % ) ) than those who were not ( 10 of 481 ( 2 % ) , p < 0.001 ) . Of the 20 % of arrests that occurred in public places , few were in places where public access defibrillators would now be available . Conclusions : The burden of out of hospital cardiac arrest is mainly in the home but most victims have premonitory symptoms . Public education to seek help urgently for new or prolonged chest pain seems the most promising method to address the problem STUDY OBJECTIVE This study correlated the delay in initiation of byst and er cardiopulmonary resuscitation ( ByCPR ) , basic ( BLS ) or advanced cardiac ( ACLS ) life support , and transport time ( TT ) to survival from prehospital cardiac arrest . This was a secondary endpoint in a study primarily evaluating the effect of bicarbonate on survival . DESIGN Prospect i ve multicenter trial . SETTING Patients treated by urban , suburban , and rural emergency medical services ( EMS ) services . PATIENTS Eight hundred and seventy-four prehospital cardiac arrest patients . INTERVENTIONS This group underwent conventional ACLS intervention followed by empiric early administration of sodium bicarbonate noting resuscitation times . Survival was measured as the presence of vital signs on emergency department ( ED ) arrival . Data analysis utilized Student 's t-test and logistic regression ( p<0.05 ) . RESULTS Survival was improved with decreased time to BLS ( 5.52 min versus 6.81 min , p=0.047 ) and ACLS ( 7.29 min versus 9.49 min , p=0.002 ) intervention , as well as difference in time to return of spontaneous circulation ( ROSC ) . The upper limit time interval after which no patient survived was 30 min for ACLS time , and 90 min for transport time . There was no overall difference in survival except at longer arrest times when considering the primary study intervention bicarbonate administration . CONCLUSION Delay to the initiation of BLS and ACLS intervention influenced outcome from prehospital cardiac arrest negatively . There were no survivors after prolonged delay in initiation of ACLS of 30 min or greater or total resuscitation and transport time of 90 min . This result was not influenced by giving bicarbonate , the primary study intervention , except at longer arrest times OBJECTIVES To compare the quality of resuscitation between those with a simplified chest compression-only cardiopulmonary resuscitation ( CPR ) program and those with a conventional CPR program . METHODS The participants were r and omly assigned to either the 120-min training program of chest compressions ( chest compression-only CPR ) or the 180-min training program of chest compressions and ventilations ( conventional CPR ) . Main outcome measures were the net number of appropriate chest compressions during the 2-min test period and the proportion of appropriate chest compressions over the theoretically attainable number one month after the training . RESULTS 223 participants were enrolled and 104 in each group completed this study . The 2-min number of appropriate chest compressions was 86.1+/-57.2 in the chest compression-only CPR group , which was significantly greater than 57.1+/-30.2 in the conventional CPR group ( p<0.001 ) . The proportion of appropriate chest compressions was higher in the chest compression-only CPR group than in the conventional CPR group ( 47.1+/-31.1 % versus 38.1+/-20.1 % , p=0.022 ) . Time without chest compressions during conventional CPR reached 85.5+/-17.0 s out of 120 s , which was significantly longer than that during chest compression-only CPR ( 33.9+/-10.0 s , p<0.001 ) . The total number of ventilations and the number of appropriate ventilations during 2 min was 2.5+/-3.0 and 0.9+/-1.6 , respectively . CONCLUSIONS A simplified chest compression-only CPR program makes it possible for the general public to perform a greater number of appropriate chest compressions than the conventional CPR program ( UMIN-CTR C0000000321 ) BACKGROUND Despite a large amount of data assessing outcomes of out-of-hospital cardiac arrests ( OHCAs ) , little information is available about physician-staffed emergency medical service ( EMS ) systems . The aim of our study was to investigate the impact of a physician on the outcome of patients after OHCA . METHODS This is a prospect i ve , observational study that included 539 consecutive patients ( 63.9 + /- 19.1 years old ; 349 males ) with OHCA in the community of Dachau ( 135,000 inhabitants ) in whom resuscitation was attempted between January 2000 and January 2006 according to Utstein style . Patients were followed up to hospital discharge . The primary end point of the study was that the patients was discharged alive from hospital . RESULTS Of 412 patients with an OHCA , 180 ( 43.7 % ) were admitted to hospital , and 47 ( 11.4 % ) were discharged alive . Resuscitation was started by a physician in 117 ( 28.4 % ) patients , by a layperson in 118 ( 28.6 % ) , or by an EMS personnel in 177 ( 43.0 % ) . A total of 18 patients ( 18.6 % ) treated by physicians , 13 patients ( 8.0 % ) treated by EMS personnel ( P = .02 vs treatment by physician ) , and 16 patients ( 16.5 % ) resuscitated by laypersons were discharged from hospital ( P = .8 vs treatment by physician ) . In 105 patients with byst and er-witnessed OHCA of cardiac origin with shockable rhythm , the discharge rate was 32.4 % ( n = 34 ) . Multivariate analysis identified ventricular fibrillation on first electrocardiogram , observed OHCA , short response time intervals but not the unit that performed the first resuscitation attempt as independent predictors of survival . CONCLUSIONS A physician on board of the advanced life support Output:	Educational polymorphisms of BLS algorithms could build unpredictable barriers between rescuers and cardiac arrest victims and might seriously limit instructors ' educational effectiveness .
MS21611	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE Little prospect i ve research exists on risk factors for diabetic foot ulcer that considers the independent effects of multiple potential etiologic agents . We prospect ively studied the effects of diabetes characteristics , foot deformity , behavioral factors , and neurovascular function on foot ulcer risk among 749 diabetic veterans with 1,483 lower limbs . RESEARCH DESIGN AND METHODS Eligible subjects included all diabetic enrollees of a general internal medicine clinic without foot ulcer , of whom 83 % agreed to participate . Baseline assessment included history and lower-limb physical examination , tests for sensory and autonomic neuropathy , and measurements of macro- and microvascular perfusion in the foot . Subjects were followed for the occurrence of a full thickness skin defect on the foot that took > 14 days to heal , with a mean follow-up of 3.7 years . RESULTS Using stepwise Cox regression analysis , the following factors were independently related to foot ulcer risk : foot insensitivity to the 5.07 monofilament ( relative risk [ 95 % CI ] ) 2.2 ( 1.5 - 3.1 ) , past history of amputation 2.8 ( 1.8 - 4.3 ) or foot ulcer 1.6 ( 1.2 - 2.3 ) , insulin use 1.6 ( 1.1 - 2.2 ) , Charcot deformity 3.5 ( 1.2 - 9.9 ) , 15 mmHg higher dorsal foot transcutaneous PO2 0.8 ( 0.7 - 0.9 ) , 20 kg higher body weight 1.2 ( 1.1 - 1.4 ) , 0.3 higher ankle-arm index 0.8 ( 0.7 - 1.0 ) , poor vision 1.9 ( 1.4 - 2.6 ) , and 13 mmHg orthostatic blood pressure fall 1.2 ( 1.1 - 1.5 ) . Higher ulcer risk was associated with hammer/claw toe deformity and history of laser photocoagulation in certain subgroups . Unrelated to foot ulcer risk in multivariate models were diabetes duration and type , race , smoking status , diabetes education , joint mobility , hallux blood pressure , and other foot deformities . CONCLUSIONS Certain foot deformities , reduced skin oxygenation and foot perfusion , poor vision , greater body mass , and both sensory and autonomic neuropathy independently influence foot ulcer risk , thereby providing support for a multifactorial etiology for diabetic foot ulceration OBJECTIVE The purpose of this study was to compare the effectiveness of a removable cast walker ( RCW ) rendered irremovable ( iTCC ) with the total contact cast ( TCC ) in the treatment of diabetic neuropathic plantar foot ulcers . RESEARCH DESIGN AND METHODS In a prospect i ve , r and omized , controlled trial , 41 consecutive diabetic patients with chronic , nonischemic , neuropathic plantar foot ulcers were r and omly assigned to one of two groups : a RCW rendered irremovable by wrapping it with a single layer of fiberglass casting material ( i.e. , an iTCC ) or a st and ard TCC . Primary outcome measures were the proportion of patients with ulcers that healed at < /=12 weeks , healing rates , complication rates , cast placement/removal times , and costs . RESULTS The proportions of patients with ulcers that healed within 12 weeks in the iTCC and TCC groups were 80 and 74 % , respectively ( 94 and 93 % , respectively , when patients who were lost to follow-up were excluded ) . Survival analysis ( healing rates ) was statistically equivalent in the two groups , as were complication rates , but with a trend toward benefit in the iTCC group . The iTCC took significantly less time to place and remove than the TCC with 39 % and 36 % reductions , respectively . There was also an overall lower cost associated with the use of the iTCC compared with the TCC . CONCLUSIONS The iTCC may be equally efficacious , faster to place , easier to use , and less expensive than the TCC in the treatment of diabetic plantar neuropathic foot ulcers OBJECTIVE To evaluate the effectiveness of at-home infrared temperature monitoring as a preventative tool in individuals at high risk for diabetes-related lower-extremity ulceration and amputation . RESEARCH DESIGN AND METHODS Eighty-five patients who fit diabetic foot risk category 2 or 3 ( neuropathy and foot deformity or previous history of ulceration or partial foot amputation ) were r and omized into a st and ard therapy group ( n = 41 ) or an enhanced therapy group ( n = 44 ) . St and ard therapy consisted of therapeutic footwear , diabetic foot education , and regular foot evaluation by a podiatrist . Enhanced therapy included the addition of a h and held infrared skin thermometer to measure temperatures on the sole of the foot in the morning and evening . Elevated temperatures ( > 4 degrees F compared with the opposite foot ) were considered to be " at risk " of ulceration due to inflammation at the site of measurement . When foot temperatures were elevated , subjects were instructed to reduce their activity and contact the study nurse . Study subjects were followed for 6 months . RESULTS The enhanced therapy group had significantly fewer diabetic foot complications ( enhanced therapy group 2 % vs. st and ard therapy group 20 % , P = 0.01 , odds ratio 10.3 , 95 % CI 1.2 - 85.3 ) . There were seven ulcers and two Charcot fractures among st and ard therapy patients and one ulcer in the enhanced therapy group . CONCLUSIONS These results suggest that at-home patient self-monitoring with daily foot temperatures may be an effective adjunctive tool to prevent foot complications in individuals at high risk for lower-extremity ulceration and amputation BACKGROUND Limited ankle dorsiflexion has been implicated as a contributing factor to plantar ulceration of the forefoot in diabetes mellitus . The purpose of this study was to compare outcomes for patients with diabetes mellitus and a neuropathic plantar ulcer treated with a total-contact cast with and without an Achilles tendon lengthening . Our primary hypothesis was that the Achilles tendon lengthening would lead to a lower rate of ulcer recurrence . METHODS Sixty-four subjects were r and omized into two treatment groups , immobilization in a total-contact cast alone or combined with percutaneous Achilles tendon lengthening , with measurements made before and after treatment , at the seven-month follow-up examination , and at the final follow-up evaluation ( a mean [ and st and ard deviation ] of 2.1 + /- 0.7 years after initial healing ) . There were thirty-three subjects in the total-contact cast group and thirty-one subjects in the Achilles tendon lengthening group . There were no significant differences in age , body-mass index , or duration of diabetes between the groups . Outcome measures were time to healing of the ulcer , ulcer recurrence rate , range of dorsiflexion of the ankle , peak torque ( strength ) of the plantar flexor muscles , and peak plantar pressures on the forefoot . RESULTS Twenty-nine ( 88 % ) of thirty-three ulcers in the total-contact cast group and all thirty ulcers ( 100 % ) in the Achilles tendon lengthening group healed after a mean duration ( and st and ard deviation ) of 41 + /- 28 days and 58 + /- 47 days , respectively ( p > 0.05 ) . ( One patient in the Achilles tendon lengthening group died before treatment was completed . ) In the first seven months of follow-up , sixteen ( 59 % ) of the twenty-seven patients in the total-contact cast group who were available for follow-up and four ( 15 % ) of the twenty-seven patients in the Achilles tendon lengthening group who were available for follow-up had an ulcer recurrence ( p = 0.001 ) . At the time of the two-year follow-up , twenty-one ( 81 % ) of the twenty-six patients in the total-contact cast group and ten ( 38 % ) of the twenty-six patients in the Achilles tendon lengthening group had ulcer recurrence ( p = 0.002 ) . Compared with the group treated with the total-contact cast , the group treated with Achilles tendon lengthening had increased dorsiflexion and it remained increased at seven months ( p < 0.001 ) . Plantar flexor peak torque also decreased after Achilles tendon lengthening ( p < 0.004 ) , but it returned to baseline after seven months . Peak plantar pressures on the forefoot during barefoot walking were reduced ( p < 0.0002 ) following Achilles tendon lengthening yet returned to baseline values within seven months after treatment . CONCLUSIONS All ulcers healed in the Achilles tendon lengthening group , and the risk for ulcer recurrence was 75 % less at seven months and 52 % less at two years than that in the total-contact cast group . Achilles tendon lengthening should be considered an effective strategy to reduce recurrence of neuropathic ulceration of the plantar aspect of the forefoot in patients with diabetes mellitus and limited ankle dorsiflexion ( < /=5 degrees ) OBJECTIVE To compare the efficacy , safety , and compliance of a nonremovable fiberglass cast boot and off-loading shoes in the treatment of diabetic plantar ulcers . RESEARCH DESIGN AND METHODS Patients ( n = 93 ) with noninfected , nonischemic plantar ulcers were included in this prospect i ve nonr and omized study . Treatment used a nonremovable fiberglass cast boot for longer st and ing and deeper ulcers ( n = 42 ) and a half shoe or heel-relief shoe for other ulcers ( n = 51 ) . We evaluated off-loading therapy , compliance , and complications in both groups . RESULTS The healing rate was significantly higher with the cast boot than with the off-loading shoe ( 81 vs. 70 % , P = 0.017 ) , with healing times of 68.6 + /- 35.1 vs. 134.2 + /- 133.0 days , respectively , and hazard ratio 1.68 ( 95 % CI 1.04 - 2.70 ) ; complete compliance with treatment was 98 vs. 10 % ( P = 0.001 ) , respectively . Secondary osteomyelitis developed in 3 patients in the cast boot group and 13 patients in the off-loading shoe group ( P = 0.026 ) . CONCLUSIONS A nonremovable fiberglass cast boot was effective in healing diabetic plantar ulcers and in decreasing the risk of secondary osteomyelitis . The cast boot forced compliance with off-loading , thus promoting healing Abstract . Aims /hypothesis : The management of charcot neuroarthropathy , a severe disabling condition in diabetic patients with peripheral neuropathy , is currently inadequate with no specific pharmacological treatment available . We undertook a double-blind r and omised controlled trial to study the effect of pamidronate , a bisphosphonate , in the management of acute diabetic Charcot neuroarthropathy . Methods : Altogether 39 diabetic patients with active Charcot neuroarthropathy from four centres in Engl and were r and omised in a double-blind placebo-controlled trial . Patients received a single infusion of 90 mg of pamidronate or placebo ( saline ) . Foot temperatures , symptoms and markers of bone turnover ( bone specific alkaline phosphatase and deoxypyridinoline crosslinks ) were measured over the 12 months , in 10 visits . All patients also had st and ard treatment of the Charcot foot . Results : Mean age of the study group ( 59 % Type II ( non-insulin-dependent ) diabetes mellitus ) was 56.3 ± 10.2 years . The mean temperature difference between active and control groups was 3.6 ± 1.7 ° C and 3.3 ± 1.4 ° C , respectively . There was a fall in temperature of the affected foot in both groups after 2 weeks with a further reduction in temperature in the active group at 4 weeks ( active and placebo vs baseline ; p = 0.001 ; p = 0.01 , respectively ) , but no difference was seen between groups . An improvement in symptoms was seen in the active group compared with the placebo group ( p < 0.001 ) . Reduction in bone turnover ( means ± SEM ) was greater in the active than in the control group . Urinary deoxypyridinoline in the pamidronate treated group fell to 4.4 ± 0.4 nmol/mmol creatinine at 4 weeks compared with 7.1 ± 1.0 in the placebo group ( p = 0.01 ) and bone-specific alkaline phosphatase fell to 14.1 ± 1.2 u/l compared with 18.6 ± 1.6 u/l after 4 weeks , respectively ( p = 0.03 ) . Conclusion /interpretation : The bisphosphonate , pamidronate , given as a single dose leads to a reduction in bone turnover , symptoms and disease activity in diabetic patients with active Charcot neuroarthropathy . [ Diabetologia ( 2001 ) 44 : 2032–2037 CONTEXT Many people with diabetes experience lower-limb ulcers . Footwear has been implicated as a primary cause of foot ulcers , yet research is limited on the efficacy of shoe and insert combinations to prevent reulceration . OBJECTIVE To determine whether extra-depth and -width therapeutic shoes used with 2 types of inserts reduce reulceration in diabetic individuals with a history of foot ulcer . DESIGN , Output:	The trials evaluating bisphosphonates reported greater reduction in foot temperature and disease activity for intervention subjects compared with controls . Another outcome of this review indicated additional beneficial effects of bisphosphonates in reducing pain and discomfort . Bisphosphonates may be useful adjuncts to st and ard management of Charcot foot by improved healing demonstrated by a reduction in disease activity indicated by skin temperature and bone destruction . Magnetic therapy may reduce deformity , joint destruction and improve mobility . CONCLUSION There is a lack of evidence supporting the use of pharmacological or non-surgical interventions with reducing lesions , ulceration , rate of surgical intervention , hospital admissions and improving the quality of life of subjects with Charcot foot . Bisphosphonates may improve the healing of Charcot foot by reducing skin temperature and disease activity of Charcot foot , when applied in addition to st and ard interventions to control the position and shape of the foot
MS21612	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objectives : Drinking green tea is associated with many health benefits , including increased fat oxidation . We tested the hypothesis that epigallocatechin-3-gallate ( EGCG ) , the main green tea catechin , increases fat oxidation in obese men . Methods : Ten healthy overweight/obese males ( body mass index 31.3±0.8 kg/m2 ) were studied in a r and omized , placebo-controlled , double-blind crossover trial . Study supplements were low EGCG ( 300 mg ) , high EGCG ( 600 mg ) , caffeine ( 200 mg ) , EGCG/caffeine ( 300 mg/200 mg ) or placebo and were taken orally for 3 days . At the third day of supplementation , O2 consumption and CO2 production was measured by indirect calorimetry to assess energy expenditure and fat oxidation over 4 h each after overnight fasting and after a st and ardized test meal . Results : Energy expenditure was not affected by any supplementation , neither after overnight fasting nor after the test meal . During the first 2 h after overnight fasting , fat oxidation increased by 7.7 ( not significant , NS ) , 15.2 ( NS ) , 26.3 ( P<0.05 vs placebo ) and 35.4 % ( P<0.01 vs placebo and low EGCG ) , for low EGCG , high EGCG , caffeine and EGCG/caffeine , respectively . During the first 2 h after the meal , the mean increase in fat oxidation was 33.3 ( P<0.05 vs placebo ) , 20.2 ( NS ) , 34.5 ( P<0.05 vs placebo ) and 49.4 % ( P<0.05 vs placebo ) for low EGCG , high EGCG , caffeine and EGCG/caffeine , respectively . Conclusions : Low EGCG increases postpr and ial fat oxidation in obese men and this to the same extent as 200 mg caffeine , whereas high EGCG does not exert this effect . Fasting fat oxidation is increased only by caffeine ( with or without EGCG ) . There is no synergism of low EGCG and 200 mg caffeine . Energy expenditure is not affected by EGCG Lack of control of food intake , excess size , and frequency of meals are critical to the development of obesity . The stomach signals satiation postpr and ially and may play an important role in control of calorie intake . Sodium alginate ( based on brown seaweed Laminaria digitata ) is currently marketed as a weight loss supplement , but its effects on gastric motor functions and satiation are unknown . We evaluated effects of 10 days treatment with alginate or placebo on gastric functions , satiation , appetite , and gut hormones associated with satiety in overweight or obese adults . We conducted a r and omized , 1:1 , placebo-controlled , allocation-concealed study in 48 overweight or obese participants with excluded psychiatric comorbidity and binge eating disorder . All underwent measurements of gastric emptying ( GE ) , fasting , and postpr and ial gastric volumes ( GVs ) , postpr and ial satiation , calorie intake at a free choice meal and selected gut hormones after 1 week of alginate ( three capsules vs. matching placebo per day , ingested 30 min before the main meal ) . Six capsules were ingested with water 30 min before the GE , GV , and satiation tests on days 8 - 10 . There were no treatment group effects on GE or volumes , gut hormones ( ghrelin , cholecystokinin ( CCK ) , glucagon-like peptide-1 ( GLP-1 ) , peptide YY ( PYY ) ) , satiation , total and macronutrient calorie intake at a free choice meal . There was no difference detected in results between obese and overweight patients . Alginate treatment for a period of 10 days showed no effect on gastric motor functions , satiation , appetite , or gut hormones . These results question the use of short-term alginate treatment for weight loss Snacking is an uncontrolled eating behavior , predisposing weight gain and obesity . It primarily affects the female population and is frequently associated with stress . We hypothesized that oral supplementation with Satiereal ( Inoreal Ltd , Plerin , France ) , a novel extract of saffron stigma , may reduce snacking and enhance satiety through its suggested mood-improving effect , and thus contribute to weight loss . Healthy , mildly overweight women ( N = 60 ) participated in this r and omized , placebo-controlled , double-blind study that evaluated the efficacy of Satiereal supplementation on body weight changes over an 8-week period . Snacking frequency , the main secondary variable , was assessed by daily self-recording of episodes by the subjects in a nutrition diary . Twice a day , enrolled subjects consumed 1 capsule of Satiereal ( 176.5 mg extract per day ( n = 31 ) or a matching placebo ( n = 29 ) . Caloric intake was left unrestricted during the study . At baseline , both groups were homogeneous for age , body weight , and snacking frequency . Satiereal caused a significantly greater body weight reduction than placebo after 8 weeks ( P < .01 ) . The mean snacking frequency was significantly decreased in the Satiereal group as compared with the placebo group ( P < .05 ) . Other anthropometric dimensions and vital signs remained almost unchanged in both groups . No subject withdrawal attributable to a product effect was reported throughout the trial , suggesting a good tolerability to Satiereal . Our results indicate that Satiereal consumption produces a reduction of snacking and creates a satiating effect that could contribute to body weight loss . The combination of an adequate diet with Satiereal supplementation might help subjects engaged in a weight loss program in achieving their objective OBJECTIVE Peptide YY3–36 ( PYY3–36 ) , a Y2 receptor agonist , and oxyntomodulin , a glucagon-like peptide 1 ( GLP-1 ) receptor agonist , are cosecreted by intestinal L-cells after each meal . Separately each hormone acts as an endogenous satiety signal and reduces appetite in humans when infused intravenously . The aim of the current study was to investigate whether the anorectic effects of PYY3–36 and oxyntomodulin can be additive . RESEARCH DESIGN AND METHODS Twelve overweight or obese human volunteers underwent a r and omized , double-blinded , placebo-controlled study . An ad libitum test meal was used to measure energy intake during intravenous infusions of either PYY3–36 or oxyntomodulin or combined PYY3–36/oxyntomodulin . RESULTS Energy intake during coadministration of PYY3–36 and oxyntomodulin was reduced by 42.7 % in comparison with the saline control and was significantly lower than that during infusions of either hormone alone . CONCLUSIONS The anorectic effects of PYY3–36 and oxyntomodulin can be additive in overweight and obese humans . Coadministration of Y2 receptor agonists and GLP-1 receptor agonists may be a useful treatment strategy for obesity Our objective was to examine the effect of a quercetin supplementation on blood pressure , lipid metabolism , markers of oxidative stress , inflammation , and body composition in an at-risk population of 93 overweight-obese volunteers aged 25 - 65 y with metabolic syndrome traits in relation to apolipoprotein ( apo ) E genotype . Participants were r and omized to receive 150 mg/d quercetin in a double-blinded , placebo-controlled , crossover trial with 6-wk treatment periods separated by a 5-wk washout period . Retrospectively , 5 apoE genotype variants were found ( epsilon2/epsilon3 , n = 3 ; epsilon3/epsilon3 , n = 60 ; epsilon3/epsilon4 , n = 23 ; epsilon2/epsilon4 , n = 4 ; and epsilon4/epsilon4 , n = 3 ) . Participants were classified into the following 3 apoE phenotypes : apoE2 ( n = 3 ) , apoE3 ( n = 60 ) , and apoE4 ( n = 26 ) . Data were analyzed for apoE3 and apoE4 subgroups . Quercetin decreased systolic blood pressure by 3.4 mm Hg ( P < 0.01 ) in the apoE3 group , whereas no significant effect was observed in the apoE4 group . Quercetin decreased serum HDL cholesterol ( P < 0.01 ) and apoA1 ( P < 0.01 ) and increased the LDL : HDL cholesterol ratio ( P < 0.05 ) in the apoE4 subgroup , whereas the apoE3 subgroup had no significant changes in these variables . Quercetin significantly decreased plasma oxidized LDL and tumor necrosis factor-alpha in the apoE3 and apoE4 groups , whereas no significant inter-group differences were found . Serum C-reactive protein and nutritional status ( body weight , waist circumference , fat mass , fat-free mass ) were unaffected compared with placebo . In conclusion , quercetin exhibited blood pressure-lowering effects in overweight-obese carriers of the apo epsilon3/epsilon3 genotype but not in carriers of the epsilon4 allele . Furthermore , quercetin supplementation result ed in a reduction in HDL cholesterol and apoA1 in apo epsilon4 carriers OBJECTIVE To assess the effects of exenatide on body weight and glucose tolerance in nondiabetic obese subjects with normal or impaired glucose tolerance ( IGT ) or impaired fasting glucose ( IFG ) . RESEARCH DESIGN AND METHODS Obese subjects ( n = 152 ; age 46 ± 12 years , female 82 % , weight 108.6 ± 23.0 kg , BMI 39.6 ± 7.0 kg/m2 , IGT or IFG 25 % ) were r and omized to receive exenatide ( n = 73 ) or placebo ( n = 79 ) , along with lifestyle intervention , for 24 weeks . RESULTS Exenatide-treated subjects lost 5.1 ± 0.5 kg from baseline versus 1.6 ± 0.5 kg with placebo ( exenatide − placebo , P < 0.001 ) . Placebo-subtracted difference in percent weight reduction was −3.3 ± 0.5 % ( P < 0.001 ) . Both groups reduced their daily calorie intake ( exenatide , −449 cal ; placebo , −387 cal ) . IGT or IFG normalized at end point in 77 and 56 % of exenatide and placebo subjects , respectively . CONCLUSIONS Exenatide plus lifestyle modification decreased caloric intake and result ed in weight loss in nondiabetic obesity with improved glucose tolerance in subjects with IGT and IFG In vitro and in vivo studies have shown that punicic acid , a type of conjugated fatty acid and the main constituent of pomegranate seed oil ( PSO ) , has anti-atherogenic effects . The present study aim ed at determining the effect of PSO treatment on serum lipid profiles . This double-blind placebo-controlled r and omised clinical trial included fifty-one hyperlipidaemic subjects , diagnosed according to National Cholesterol Education Program definition , and r and omly assigned to the PSO and the control groups . The PSO and placebo groups received 400 mg PSO and placebo twice daily , respectively and were followed up for 4 weeks . Serum concentrations of lipids and lipoproteins were measured before and 4 weeks after intervention . Mean concentration of TAG and the TAG : HDL cholesterol ( HDL-C ) ratio were significantly decreased after 4 weeks in the PSO group as compared with baseline values ( 2.75 ( sd 1.40 ) v. 3.45 ( sd 1.56 ) mmol/l , P = 0.009 and 5.7 ( sd 4.6 ) v. 7.5 ( sd 5.0 ) , P = 0.031 , respectively ) . The treatment effect was statistically significant in the PSO group as compared with controls in diminution of cholesterol : HDL-C ratio ( 5.4 ( sd 1.5 ) v. 5.9 ( sd 1.4 ) , P < 0.05 ) adjusted for baseline values . We found a mean difference for PSO v. placebo in HDL-C concentration ( 0.13 v. - 0.02 mmol/l ) and cholesterol : HDL-C ratio ( - 0.42 v. 0.01 , P < 0.05 ) . Serum cholesterol , LDL cholesterol and glucose concentrations and body composition variables remained unchanged . It is concluded that administration of PSO for 4 weeks in hyperlipidaemic subjects had favourable effects on lipid profiles including TAG and TAG : HDL-C ratio Dietary supplementation with whole blueberries in a pre clinical study result ed in a reduction in glucose concentrations over time . We sought to evaluate the effect of daily dietary supplementation with bioactives from blueberries on whole-body insulin sensitivity in men and women . A double-blinded , r and omized , and placebo-controlled clinical study design was used . After screening to resolve study eligibility , baseline ( wk 0 ) ins Output:	Studies with Nigella Sativa , Camellia Sinensis , Crocus Sativus L , Seaweed laminaria Digitata , Xantigen , virgin olive oil , Catechin enriched green tea , Monoselect Camellia , Oolong tea , Yacon syrup , Irvingia Gabonensi , Weighlevel , RCM-104 compound of Camellia Sinensis , Pistachio , Psyllium fibre , black Chinese tea , sea buckthorn and bilberries show significant decreases in body weight . Only , alginate-based brown seaweed and Laminaria Digitata caused an abdominal bloating and upper respiratory tract infection as the side effect in the trial group . In conclusion , Nigella Sativa , Camellia Synensis , Green Tea , and Black Chinese Tea seem to have satisfactory anti-obesity effects .
MS21613	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To assess whether IV tramadol before outpatient hysteroscopy could reduce procedure-related pain . DESIGN A r and omized double-blind placebo controlled trial . SETTING Outpatient Hysteroscopy Centre in the Department of Obstetrics and Gynaecology of Cagliari University . PATIENT(S ) Fifty healthy , parous , women who underwent outpatient diagnostic hysteroscopy and endometrial biopsy . INTERVENTION(S ) R and om IV infusion of tramadol or placebo before hysteroscopy and endometrial biopsy were performed . MAIN OUTCOME MEASURE(S ) Visual analogue scale of pain was measured both immediately after and 15 minutes after the procedure . Stress hormones ( ACTH , cortisol ) , blood pressure , and heart frequency were evaluated before , during , and 15 minutes after the procedure . RESULT ( S ) In the tramadol group , the visual analogue scale of pain was significantly lower than in the placebo group both immediately after the procedure and 15 minutes later . Basal levels of ACTH and cortisol did not differ between the groups . In both groups , the ACTH levels remained unchanged during the study , and the cortisol levels were higher 15 minutes after the procedure than before the procedure . Procedure time , heart frequency , blood pressure , and adverse effects did not differ between the groups . CONCLUSION ( S ) In parous women without uterine malformations , a treatment with tramadol before hysteroscopy and endometrial biopsy appears to be capable of reducing the pain and discomfort that are associated with this procedure OBJECTIVE The aim of this study was to compare traditional hysteroscopy with mini-hysteroscopy in terms of compliance , side effects and diagnostic efficacy . STUDY DESIGN We prospect ively considered 950 female c and i date s for an IVF programme . All women underwent outpatient hysteroscopy ; in 602 cases ( Group A ) a mini-hysteroscope was employed ; in 348 women ( Group B ) a 5-mm hysteroscope was adopted . RESULTS Cavity findings were similar in both groups . Endometrial polyps and uterine septum seem to be more frequent in our infertile patients than in the general population . No significant differences in terms of side effects were found between the groups . Mean visual analogue pain scale score was significantly lower in the patients of Group A than in those of Group B ( p<0.001 ) . CONCLUSIONS Office mini-hysteroscopy is a very effective diagnostic tool in an infertility work-up and is more widely accepted than traditional hysteroscopy . Routine use of the technique should be considered OBJECTIVE To compare the efficacy of two modalities of local anesthesia for diagnostic hysteroscopy in different steps of the procedure in terms of pain control and time required for the examination . STUDY DESIGN One hundred eighty women undergoing diagnostic hysteroscopy were included in the study and r and omly allocated to one of two groups . Group A ( n = 88 ) , treated with prilocaine plus lidocaine cream , and group B ( n = 92 ) , treated with lidocaine spray , were compared with group C , a control group ( n = 165 ) , including all the hysteroscopies performed without anesthesia in the same period . Duration of the hysteroscopic examination was recorded ; intensity of pain induced by the procedure and shoulder pain 10 minutes after the end of the examination were recorded for all patients on the basis of a four-point pain scale . RESULTS Duration of the procedure required was two minutes in a significantly lower percentage of patients in group A as compared to groups B and C. Furthermore , in group A we found a significant reduction in pain at placement of the tenaculum in comparison to groups B and C. In groups A and B , no patient experienced a " very painful " grade of pain versus 4.8 % in group C. The vasovagal reaction rate was also significantly lower in both treated groups in comparison to the control group . Furthermore , the intensity of shoulder pain was significantly lower in the group receiving prilocaine plus lidocaine cream as compared to the other two groups . CONCLUSION Local anesthesia has a beneficial effect , at least in those hysteroscopies presumed to be , for whatever reasons , more cumbersome to perform . Prilocaine plus lidocaine cream was more effective than lidocaine spray in decreasing pain at placement of the tenaculum and shoulder pain after the procedure BACKGROUND Diagnostic hysteroscopy is not widely performed in the office setting , one of the reasons being the discomfort produced by the procedure . This r and omized controlled trial was performed to evaluate the effects of instrument diameter , patient parity and surgeon experience on the pain suffered and success rate of the procedure . METHODS Patients were r and omly assigned to undergo office diagnostic hysteroscopy either with 5.0 mm conventional instruments ( n=240 ) or with 3.5 mm mini-instruments ( n=240 ) . Procedures were stratified according to patient parity and surgeon 's previous experience . The pain experienced during the procedure ( 0 - 10 ) , the quality of visualization of the uterine cavity ( 0 - 3 ) and the complications were recorded . The examination was considered successful when the pain score was < 4 , visualization score was > 1 and no complication occurred . RESULTS Less pain , better visualization and higher success rates were observed with mini-hysteroscopy ( P < 0.0001 , P < 0.0001 and P < 0.0001 , respectively ) , in patients with vaginal deliveries ( P < 0.0001 , P < 0.0001 and P < 0.0001 , respectively ) and in procedures performed by experienced surgeons ( P=0.02 , P = NS and P = NS , respectively ) . The effects of patient parity and surgeon experience were no longer important when mini-hysteroscopy was used . CONCLUSIONS Our data demonstrate the advantages of mini-hysteroscopy and the importance of patient parity and surgeon experience , suggesting that mini-hysteroscopy should always be used , especially for inexperienced surgeons and when difficult access to the uterine cavity is anticipated . They indicate that mini-hysteroscopy can be offered as a first line office diagnostic procedure STUDY OBJECTIVE To assess acceptability and cardiovascular complications of hysteroscopy performed with minihysteroscopes compared with those performed with conventional hysteroscopes . DESIGN Prospect i ve , r and omized clinical trial ( Canadian Task Force classification I ) . SETTING Academic research center . PATIENTS One hundred women with abnormal uterine bleeding . INTERVENTIONS Hysteroscopy with a 3.5-mm minihysteroscope or conventional 5-mm endoscope with no anesthesia . MEASUREMENTS AND MAIN RESULTS Duration of examinations , pain , and occurrence of vasovagal reactions were recorded . Pain was assessed by visual analog scale ranging from zero to 20 before ( pain expectancy ) and at the end of the procedure . Occurrence of vasovagal reactions was assessed by monitoring blood pressure and pulse rate at 1-minute intervals during the procedure . A heart rate of less than 60/minute or a reduction greater than 20 % compared with baseline was considered a vasovagal reaction ; similarly , a reduction in blood pressure exceeding baseline value by 20 % was considered a result of vagal stimulation . Mean duration was shorter for minihysteroscopy than for conventional hysteroscopy . The mean ( SD ) level of pain experienced during minihysteroscopy also was significantly lower ( 0.76 + /- 0.65 vs 1.46 + /- 0.86 , 95 % CI-1.0 - 0.4 , p < 0.0001 ) . The number of instrumentally recorded ( 1 vs 11 cases ) and clinical vasovagal reactions ( 0 vs 6 cases ) was also significantly lower in the minihysteroscopy group than in the conventional hysteroscopy group ( p < 0.002 and < 0.02 , respectively ) . CONCLUSION New-generation minihysteroscopes make hysteroscopy easier and less painful , and carry a lower risk of vasovagal reactions than hysteroscopy performed with conventional instruments . In our experience , minihysteroscopy with vaginoscopic approach and saline distention is well tolerated , effective , and a true outpatient procedure Purpose Dilatation and curettage is frequently performed in gynecological practice . Aim of this prospect i ve r and omized double-blind placebo-controlled study was to evaluate the safety and efficacy of oral misoprostol to prime non-pregnant cervix before this procedure . Method Women requiring dilatation and curettage were included in the study . Exclusion criteria were visible growth in cervix or vagina , pregnancy , allergy to prostagl and ins , some medical disorders . Each participant was instructed to take either 400 µg of misoprostol or placebo orally 12 h before the procedure . Primary outcome measure was : diameter of the largest negotiable Hegar ’s dilator through internal os without any resistance at the beginning of the procedure . Secondary outcome measures were : percentage of women with initial cervical dilatation of ≥5 mm , time required for optimum cervical dilatation , percentage of failed procedures and complications . t test , Chi-square test and Fisher ’s test were used to compare the variables . Result Misoprostol significantly increased baseline cervical diameter in the pre-menopausal group ( p < 0.001 ) , but not in post-menopausal subjects ( p = 0.1 ) and reduced time required for cervical dilatation in both pre- and post-menopausal women . The number of patients achieving initial cervical dilatation ≥5 mm was significantly greater in pre-menopausal subjects receiving misoprostol , but not significant in post-menopausal ones . The drug was also found to be effective in both nulliparous and multiparous patients . Side effects were comparable between two groups . Only nausea and vomiting were more frequent in post-menopausal misoprostol group than placebo ( p = 0.018 ) . Conclusion Four hundred micrograms of oral misoprostol 12 h prior to dilation and curettage was found to be beneficial in cervical priming in pre-menopausal subjects . It was also found to be effective irrespective of the parity of the patients OBJECTIVE : To compare a “ no touch ” approach to diagnostic hysteroscopy without anesthesia with traditional diagnostic hysteroscopy after intracervical injection of mepivacaine hydrochloride 3 % . METHODS : A total of 130 women undergoing diagnostic hysteroscopy were included in the study and were r and omized , using a computer-generated r and omization list to one of two treatment groups in a ratio of 2:1 . Eighty-three women underwent hysteroscopy without speculum , tenaculum , or anesthesia . Forty-seven women received intracervical anesthesia with 10 mL of 3 % mepivacaine hydrochloride solution injected at two sites ( 3:00 and 9:00 positions ) and underwent traditional hysteroscopy . Hysteroscopy was performed using a rigid 3.7-mm hysteroscope and a medium of 0.9 % saline , and the image was transmitted to a screen visible to the patient . A visual analog scale ( VAS ) consisting of a 10-cm line was used to assess the intensity of pain experienced during and after the procedure . Overall patient satisfaction was assessed during , immediately after , 15 minutes later , and 3 days after hysteroscopy . RESULTS : The mean pain score was significantly lower in the group without the use of speculum , tenaculum , or anesthesia ( VAS1 : 3.8±2.7 versus 5.34±3.23 , P=.01 ; VAS2 : 3.02±2.50 versus 4.57±3.30 , P=.008 ) . Patient satisfaction rate was similar in both groups . CONCLUSION : Patients reported significantly less pain with the altered approach to diagnostic hysteroscopy compared with patients undergoing the traditional procedure with anesthesia . This new approach can therefore be considered as a useful hysteroscopic technique . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00319410 LEVEL OF EVIDENCE : PURPOSE to compare the pain reported by patients su bmi tted to hysteroscopy by the st and ard technique with carbon dioxide ( CO2 ) and to vaginal hysteroscopy with physiological saline ( 0.9 % NaCl ) . METHODS this was a prospect i ve cohort study conducted at an ambulatory hysteroscopy service . A total of 117 patients with indication for the exam were included , being r and omly assigned to one of the groups . All patients answered an epidemiological question naire and scored the pain expected before the exam and that felt after the end of the procedure on a verbal pain scale from 0 to 10 . A speculum , traction of the cervix , insertion of a 30 masculine light source and a diagnostic shirt with a total diameter of 5 mm were used for the st and ard technique . The cavity was distended with CO2 under a pressure of 100 mmHg controlled with a hysteroflator , and a biopsy was obtained with a Novak curette . Vaginoscopy was performed without a touch by distention of the vagina with fluid , direct visualization of the cervix and introduction of the light source with two continuous-flow shirts , with an accessory channel with an oval profile , the whole set measuring 5 mm in diameter . The medium distention was 0.9 % NaCl and the pressure used was that considered to be necessary for an adequate visualization of the canal and of the cavity with an external pneumatic pressurizer . The biopsy was obtained in a directed manner using an endoscopic clamp . The mean and st and ard deviation were calculated for the quantitative variables and the frequency was calculated for the qualitative variables . The Student 's t-test was used to compare the means , and the chi Output:	Results revealed a high prevalence of pain in outpatient mini-hysteroscopy . Conclusions Office mini-hysteroscopy is painful
MS21614	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background To analyze how lidocaine 40 mg mixed prevents injection pain of propofol affects the onset time of rocuronium , tracheal intubating conditions and intubation related hemodynamic changes . Methods This study consisted of 70 patients with an American Society of Anesthesiologists ( ASA ) physical status class 1 or 2 for general anesthesia . All the patients were r and omly allocated into two groups : propofol 2 mg/kg plus normal saline 2 ml ( Group C ) and propofol 2 mg/kg plus 2 % lidocaine 40 mg ( Group L ) . Each group was administrated intravenously during induction and the patient was intubated 1 minute after an injection of 0.6 mg/kg of rocuronium . The time at disappearance of the first twitch and intubation scores were recorded . Also , blood pressure and heart rate were measured at the baseline , after intravenous injection of propofol , before intubation , and at 0 , 1 , 2 , 3 and 5 minutes after intubation . Results There were no significant differences between group C and L ( P > 0.05 ) . Conclusions 40 mg of lidocaine mixed with propofol to prevent injection pain did not affect the onset time of rocuronium , intubating conditions and intubation related hemodynamic changes The aim of this study was to determine whether pretreatment with alkalinised lignocaine reduced the incidence and severity of pain during propofol injection . This prospect i ve , r and omised , double-blind study included 300 adult , American Society of Anesthesiologists physcial status I to II patients undergoing elective surgery . Patients were r and omly allocated to one of three groups : Group L received 0.05 ml/kg of 1 % lignocaine ( 5 ml normal saline + 5 ml 2 % lignocaine ) , Group A received 0.05 ml/kg alkalinised lignocaine ( 5 ml 2 % lignocaine + 1 ml 8.4 % NaHCO3 + 4 ml normal saline ) , and Group S , the control group , was given the same amount of normal saline ( NaCl 0.9 % ) . All drugs were given as a bolus over 20 seconds before propofol administration . A blinded research er assessed the patient 's pain level using a four-point scale . The pain score [ median ( range ) ] and the incidence of pain in Group A ( 6 % ) was significantly lower than in groups L ( 41 % ) and S ( 88 % , P < 0.001 ) . In addition , the pain score and the incidence of pain were found to be significantly different between Group L and Group S ( P < 0.001 ) . The incidence of moderate and severe pain were greater in Group S when compared with groups A and L ( P < 0.001 ) . Intravenous pretreatment with alkalinised lignocaine appears to be effective in reducing the pain during propofol injection Pain on injection , reported in 28 - 90 % of patients , is one of the most described side effects of the intravenous application of propofol . Many different approaches have been used in attempts to minimize propofol induced pain , with varied results . Using a r and omized , double-blind protocol design , the author-section pain following the administration of two different particle size formulations of propofol with or without lidocaine in 388 nonpremedicated ASA I-II adult patients scheduled for elective surgery under general anesthesia . Patients were allocated r and omly to receive either a small particle size lipid emulsion of propofol ( Anepol : average particle size 140.5 nm ) , or st and ard propofol ( Propofol : average particle size 193.3 nm ) , by dividing into 4 groups . Group 1 received 2 ml NaCl 0.9 % and Propofol , group 11 received 2 ml lidocaine 2 % and Propofol , group III received 2 ml NaCl 0.9 % and Anepol and group IV received 2 ml lidocaine 2 % and Anepol into a dorsal vein of the h and . Pain during propofol injection was evaluated over 5 - 10 seconds , until loss of conscious , using a four point scale . Sixty-seven patients ( 69.1 % ) complained of pain in group 1 , as compared with 50 % , 41.2 % and 39.2 % in group II , III and IV ( p < 0.05 ) . The reported severity of injection pain was not significantly different between the groups . The authors conclude that small particle size propofol causes less pain on injection than st and ard propofol BACKGROUND Propofol formulated with medium- and long-chain triglycerides ( MCT/LCT ) causes less pain on injection than st and ard Propofol , but the incidence of pain persists between 28 and 67 percent . Such a broad range begs the question so the authors wanted to clarify whether the addition of lidocaine to medium- and long-chain triglyceride emulsion propofol results in any clinical ly significant lessening of pain on injection . The authors conducted a r and omized , prospect i ve , double-blinded study to compare the injection pain felt following the administration of propofol-MCT/LCT ( Propofol-Lipuro ) to propofol-MCT/LCT plus 20 mg lidocaine for the induction of anesthesia . MATERIAL AND METHOD The present study included 270 non-premedicated ASA I-II adult patients scheduledfor elective surgery under general anesthesia . Patients were allocated r and omly into two groups to receive either propofol-MCT/LCT alone or propofol-MCT/LCT plus 20 mg lidocaine . The study solution was injected at 1 mL/second by one anesthesiologist and patients grade d any associated pain using a four-point scale . RESULTS The overall incidence of pain on injection was 31/133 ( 23 % ) in the propofol-MCT/LCT plus lidocaine group vs. 45/135 ( 33 % ) in the propofol-MCT/LCT alone group . The difference in the incidence of pain on injection between groups failed to achieve statistical significance ( p = 0.23 ) and no significant difference in intensity of pain between the two study groups occurred CONCLUSIONS The authors concluded that the addition of lidocaine ( 20 mg ) to the propofol-MCT/LCT does not significantly reduce the incidence or severity of the pain on injection BACKGROUND Propofol is commonly used for induction and maintenance of anesthesia , but pain at the site of intravenous injection is a clinical problem . We studied the effectiveness of local cooling and pretreatment with lidocaine for prevention of injection pain of propofol . METHODS A total of 226 adult patients scheduled to receive general anesthesia were assigned r and omly to four groups : a control group receiving no prophylactic intervention , a cooling group receiving topical cooling , a lidocaine group receiving 1 mg x kg(-1 ) lidocaine , and a lidocaine plus cooling group receiving topical cooling and 1 mg x kg(-1 ) lidocaine . A 20 gauge intravenous catheter was inserted into the peripheral vein at the radial side of the forearm . After prophylactic intervention had been performed , 1 - 2 mg x kg(-1 ) MCT/LCT propofol was injected . Patients were asked to grade the pain as none , mild , moderate , or severe . RESULTS The incidence of propofol-induced pain was significantly higher in the control group ( 39 % ) than in the other three groups ( 17 % in the cooling group , 16 % in the lidocaine group and 8 % in the lidocaine plus cooling group ) . However , there were no significant differences between the three groups with different prophylactic interventions . CONCLUSIONS The results suggest that cooling and pretreatment with lidocaine reduce the incidence of pain upon propofol injection BACKGROUND Pain on injection is a recognized adverse event ( AE ) with propofol , an agent used to induce general anesthesia in surgical patients . Lidocame ( LID ) has been found efficacious in reducing pain on injection of propofol ; however , this type of pain may not be completely eliminated with LID . Metoclopramide ( MET ) is a dopamine receptor agonist with antiemetic and prokinetic properties used for the treatment of nausea and facilitation of gastric emptying in patients with gastroparesis . MET also has local anesthetic properties similar to those of LID . OBJECTIVE The aim of this study was to examine the effects of LID administered with 3 different doses of MET or saline on pain on injection of propofol in Japanese adults undergoing elective surgery . METHODS This r and omized , double-blind study was conducted at the Department of Anesthesiology , University of Tsukuba Institute of Clinical Medicine , Tsukuba , Japan . Japanese patients aged 20 to 67 years who were scheduled to undergo elective surgery were eligible for participation . Patients were r and omized to receive N administration of LID 40 mg + MET 2.5 , 5 , or 10 mg or saline . A rubber tourniquet was used to perform 1 minute of venous occlusion before administration of the study and control drugs , and then 25 % of the total calculated dose of propofol ( 2 mg/kg ) was injected into the dorsal vein of the h and through a 20-G N cannula at a rate of 1 mL/s . During a 10-second pause before the induction of anesthesia , patients were question ed by a blinded investigator about the pain intensity on injection . Pain intensity was assessed through the use of a 4-point verbal rating scale , with scores ranging from 0 ( no pain ) to 3 ( severe pain ) . Incidence and intensity of pain ( as assessed by mean pain scores ) were determined in each of the 4 study groups . Extrapyramidal reactions and injection-site AEs , including pain , edema , wheals , and inflammation occurring up to 24 hours after surgery were recorded by a blinded investigator . RESULTS The study enrolled 240 patients ( 126 men , 114 women ; mean [ SD ] age , 43 [ 13 ] years [ range , 20 - 67 years ] ; mean [ SD ] height , 160 [ 8 ] cm [ 133 - 181 cm ] ; mean [ SD ] body weight , 57 [ 10 ] kg [ range , 33 - 85 kg ] ) . There were 60 patients r and omized to each of the 4 study groups , which were comparable in distribution of demographic characteristics . Incidence of propofol-induced pain was significantly lower , but the intensity of pain was not less , in the groups that received LID/MET 40/5 or 40/10 ( both , 5 % ) compared with those who received LID/MET 40/2.5 or LID/saline ( 18 % and 20 % , respectively ) ( all , P < 0.05 ) . There were no reports of injection-site AEs or extrapyramidal reactions after injection of the control or study drugs in any of the study groups . CONCLUSION Among these 240 Japanese patients undergoing elective surgery , N administration of LID/MET 40/5 or 40/10 was associated with lower incidence , but not lower mean pain intensity scores , of pain on injection of propofol than LID/MET 40/2.5 or LID/saline before induction of anesthesia A r and omised , double‐blind , controlled trial was undertaken to compare three different methods of reducing pain during the intravenous injection of propofol . In 101 patients undergoing daycase surgery , verbal rating scores , for pain during injection of propofol were compared immediately after intravenous pretreatment with ketorolac 10 mg , lignocaine 10 mg or saline . Neither pain during injection ( p = 0.129 ) , nor venous sequelae at 7 days postoperatively were significantly different between the three treatments . Pain during propofol injection remains a confounding clinical problem Background : Several commercial formulations of propofol are available . The primary outcome of this study was the required dose of propofol alone or combined with lidocaine to achieve induction of general anesthesia . Methods : This multicenter , double-blinded trial r and omized patients ( American Society of Anesthesiologists physical status I – III ) just before elective surgery with the use of a computer-generated list . Three different propofol 1 % formulations — Diprivan ® ( Astra-Zeneca , Cheshire , United Kingdom ) , Propofol ® ( Fresenius-Kabi AG , Bad Homburg , Germany ) , and Lipuro ® ( B-Braun , Melshungen AG , Germany)—were compared with either placebo ( saline solution ) or lidocaine 1 % mixed to the propofol solution . Depth of anesthesia was automatically guided by bispectral index and by a computerized closed-loop system for induction , thus avoiding dosing bias . The authors recorded the total dose of propofol and duration of induction and the patient ’s discomfort through a behavioral scale ( facial expression , verbal response , and arm withdrawal ) ranging from 0 to 6 . The authors further evaluated postoperative recall of pain using a Visual Analog Scale . Results : Of the 227 patients enrolled , 217 were available for analysis . Demographic characteristics were similar in each group . Propofol ® required a higher dose for induction ( 2.2 ± 0.1 mg/kg ) than Diprivan ® ( 1.8 ± 0.1 mg/kg ) or Lipuro ® ( 1.7 ± 0.1 mg/kg ; P = 0.02 ) . However , induction doses were similar when propofol formulations were mixed with lidoca Output:	Currently available data from RCTs are sufficient to confirm that both lidocaine admixture and pretreatment were effective in reducing pain on propofol injection . Furthermore , there were no significant differences of effect between the two techniques
MS21615	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : Sustained hypotension , cardiogenic shock , and heart failure all imply a poor prognosis in acute myocardial infa rct ion ( MI ) . We assessed the benefit of adding 48 hours of intra-aortic balloon counterpulsation ( IABP ) to st and ard treatment for MI , in an international trial among hospitals without primary angioplasty capabilities . Methods : We r and omized 57 patients with MI complicated by sustained hypotension , possible cardiogenic shock , or possible heart failure to receive either fibrinolytic therapy and IABP or fibrinolysis alone . The primary end point was all-cause mortality at 6 months . Results : In all , IABP was inserted in 27 of 30 assigned patients a median 30 minutes after fibrinolysis began and continued for a median 34 hours . Of the 27 patients assigned to fibrinolysis alone , 9 deteriorated such that IABP was required . The IABP group was at slightly higher risk at baseline , but the incidence of the primary end point did not differ significantly between groups ( 34 % for combined treatment versus 43 % for fibrinolysis alone ; adjusted P = 0.23 ) . Patients with Killip class III or IV showed a trend toward greater benefit from IABP ( 6-month mortality 39 % for combined therapy versus 80 % for fibrinolysis alone ; P = 0.05 ) . Conclusions : While early IABP use was not associated with a definitive survival benefit when added to fibrinolysis for patients with MI and hemodynamic compromise in this small trial , its use suggested a possible benefit for patients with the most severe heart failure or hypotension . Abbreviated Abstract . We assessed the benefit of adding 48 hours of intra-aortic balloon counterpulsation to fibrinolytic therapy among 57 patients with acute myocardial infa rct ion complicated by sustained hypotension , possible cardiogenic shock , or possible heart failure . The primary end point , mortality at 6 months , did not differ between groups ( 34 % for combined treatment versus 43 % for fibrinolysis alone [ n = 27 ] ; adjusted P = 0.23 ) , although patients with Killip class III or IV did show a trend toward greater benefit from IABP ( 39 % for combined therapy versus 80 % for fibrinolysis ; P = 0.05 ) Objective : Patients undergoing percutaneous coronary intervention ( PCI ) for acute myocardial infa rct ion with cardiogenic shock ( CS ) are often treated with intra-aortic balloon pump counterpulsation ( IABP ) , even though the evidence to support this is limited . We determined whether IABP as an addition to PCI-centered therapy ameliorates multiorgan dysfunction syndrome ( MODS ) in patients with acute myocardial infa rct ion complicated by CS . Design : A prospect i ve , r and omized , controlled , open-label clinical trial recruiting patients between March 2003 and June 2004 ( Clinical Trials.gov ID NCT00469248 ) . Setting : Tertiary care university hospital . Patients and Interventions : Forty-five consecutive patients with AMI and CS undergoing PCI were r and omized to treatment with or without IABP . Measurements and Main Results : Acute Physiology and Chronic Health Evaluation ( APACHE ) II scores ( primary outcome measure ) , hemodynamic values , inflammatory markers , and plasma brain natriuretic peptide ( BNP ) levels ( secondary outcomes ) were collected over 4 days from r and omization . The prospect i ve hypothesis was that adding IABP therapy to “ st and ard care ” would improve CS-triggered MODS . The addition of IABP to st and ard therapy did not result in a significant improvement in MODS ( measured by serial APACHE II scoring over 4 days ) . IABP use had no significant effect on cardiac index or systemic inflammatory activation , although BNP levels were significantly lower in IABP-treated patients . Initial and serial APACHE II scoring correlated with mortality better than cardiac index , systemic inflammatory state , and BNP levels in this group of patients . Nonsurvivors had significantly higher initial APACHE II scores ( 29.9 ± 2.88 ) than survivors ( 18.1 ± 1.66 , p < .05 ) . Nevertheless , discrepancies among patients within the groups can not be ruled out and might interfere with our results . Conclusions : In this r and omized trial addressing addition of IABP in CS patients , mechanical support was associated only with modest effects on reduction of APACHE II score as a marker of severity of disease , improvement of cardiac index , reduction of inflammatory state , or reduction of BNP biomarker status compared with medical therapy alone . However , the limitations of our present trial preclude any definitive conclusion , but request for a larger prospect i ve , r and omized , multicentered trial with mortality as primary end point BACKGROUND AND AIM Despite major advances in the treatment of heart failure , cardiogenic shock ( CGS ) remains associated with substantial mortality . Recent data suggest that the T and emHeart percutaneous ventricular assist device ( pVAD ) may be useful in the management of CGS . The aim of this prospect i ve r and omized study was to test the hypothesis that the T and emHeart ( pVAD ) provides superior hemodynamic support compared with intraaortic balloon pumping ( IABP ) . METHODS Forty-two patients from 12 centers presenting within 24 hours of developing CGS were included in the study and treated in an initial roll-in phase ( n = 9 ) or r and omized to treatment with IABP ( n = 14 ) or T and emHeart pVAD ( n = 19 ) . Thirty patients ( 71 % ) had persistent CGS despite having an IABP in place at the time of study enrollment . RESULTS Cardiogenic shock was due to myocardial infa rct ion in 70 % of the patients and decompensated heart failure in most of the remaining patients . The mean duration of support was 2.5 days . Compared with IABP , the T and emHeart pVAD achieved significantly greater increases in cardiac index and mean arterial blood pressure and significantly greater decreases in pulmonary capillary wedge pressure . Overall 30-day survival and severe adverse events were not significantly different between the 2 groups . CONCLUSION In patients presenting within 24 hours of the development of CGS , T and emHeart significantly improves hemodynamic parameters , even in patients failing IABP . Larger-scale studies are required to assess the influence of improved hemodynamics on survival BACKGROUND In current international guidelines the recommendation for intra-aortic balloon pump ( IABP ) use has been down grade d in cardiogenic shock complicating acute myocardial infa rct ion on the basis of registry data . In the largest r and omised trial ( IABP-SHOCK II ) , IABP support did not reduce 30 day mortality compared with control . However , previous trials in cardiogenic shock showed a mortality benefit only at extended follow-up . The present analysis therefore reports 6 and 12 month results . METHODS The IABP-SHOCK II trial was a r and omised , open-label , multicentre trial . Patients with cardiogenic shock complicating acute myocardial infa rct ion who were undergoing early revascularisation and optimum medical therapy were r and omly assigned ( 1:1 ) to IABP versus control via a central web-based system . The primary efficacy endpoint was 30 day all-cause mortality , but 6 and 12 month follow-up was done in addition to quality -of-life assessment for all survivors with the Euroqol-5D question naire . A masked central committee adjudicated clinical outcomes . Patients and investigators were not masked to treatment allocation . Analysis was by intention to treat . This trial is registered at Clinical Trials.gov , NCT00491036 . FINDINGS Between June 16 , 2009 , and March 3 , 2012 , 600 patients were assigned to IABP ( n=301 ) or control ( n=299 ) . Of 595 patients completing 12 month follow-up , 155 ( 52 % ) of 299 patients in the IABP group and 152 ( 51 % ) of 296 patients in the control group had died ( relative risk [ RR ] 1·01 , 95 % CI 0·86 - 1·18 , p=0·91 ) . There were no significant differences in reinfa rct ion ( RR 2·60 , 95 % CI 0·95 - 7·10 , p=0·05 ) , recurrent revascularisation ( 0·91 , 0·58 - 1·41 , p=0·77 ) , or stroke ( 1·50 , 0·25 - 8·84 , p=1·00 ) . For survivors , quality -of-life measures including mobility , self-care , usual activities , pain or discomfort , and anxiety or depression did not differ significantly between study groups . INTERPRETATION In patients undergoing early revascularisation for myocardial infa rct ion complicated by cardiogenic shock , IABP did not reduce 12 month all-cause mortality . FUNDING German Research Foundation ; German Heart Research Foundation ; German Cardiac Society ; Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte ; University of Leipzig -- Heart Centre ; Maquet Cardiopulmonary ; Teleflex Medical OBJECTIVES Our goal was to describe the functional status of cardiogenic shock survivors , identify the correlates of cardiogenic shock , and compare global quality of life and functional status of patients r and omly assigned to treatment with emergency revascularization ( ERV ) versus initial medical stabilization ( IMS ) . BACKGROUND Historically , the hospital survival rate of patients with cardiogenic shock complicating acute myocardial infa rct ion ( MI ) has been very low . Shock survivors are salvaged from a critically ill state , and their later functional status is not well documented . The SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK ( SHOCK ) trial showed significantly improved one-year survival after ERV compared with IMS . METHODS The SHOCK trial survivors completed interviews at 2 weeks after discharge and at 6 and 12 months after MI . Functional status assessment included the Multidimensional Index of Life Quality and New York Heart Association ( NYHA ) congestive heart failure functional class . RESULTS Eighty-seven percent of one-year survivors of the SHOCK trial were in NYHA functional class I or II . Between two weeks after discharge and one year after MI , improvement was similar in the two treatment groups ( 18 % overall ) , but fewer patients remained stable ( 44 % vs. 71 % ) , and more patients worsened or died ( 34 % vs. 15 % ) in the IMS group compared with those assigned to ERV . Assignment to ERV was the only independent predictor of outcome at one year . CONCLUSIONS Although one-year mortality after ERV is still high ( 54 % ) , most survivors have good functional status . The ERV patients have a lower rate of deterioration than IMS patients . The level of recovery for shock patients undergoing ERV is similar to that of historical controls not in cardiogenic shock undergoing elective revascularization Background Aortic counterpulsation has been observed to reduce the rate of reocclusion of the infa rct -related artery after patency has been restored during acute myocardial infa rct ion in observational studies . To evaluate the benefit-to-risk ratio of aortic counterpulsation during the early phase of myocardial infa rct ion , a multicenter r and omized clinical trial was performed . Methods and Results Patients who had patency restored during acute cardiac catheterization within the first 24 hours of onset of myocardial infa rct ion were r and omly assigned to aortic counterpulsation for 48 hours versus st and ard care . Intravenous heparin was used similarly in both groups and was continued for a median ( 25th , 75th percentile ) of 5 ( 2,7 ) days . A total of 182 patients were enrolled ; 96 were assigned to aortic counterpulsation and 86 to st and ard care . Repeat cardiac catheterization was performed at a median of 5 ( 4,6 ) days after r and omization in 89 % of patients assigned to aortic counterpulsation and in 90 % of control patients . Patients r and omized to aortic counterpulsation had similar rates of severe bleeding complications ( 2 % versus 1 % ) , number of units of blood transfused ( mean , 1.3±2.6 versus 0.9±1.8 units ) , and vascular repair or thrombectomy ( 5 % versus 2 % ) compared with patients treated in a conventional manner . Patients r and omized to aortic counterpulsation had significantly less reocclusion of the infa rct -related artery during follow-up compared with control patients ( 8 % versus 21 % , P<.03 ) . In addition , there was a significantly lower event rate in patients assigned to aortic counterpulsation in terms of a composite clinical end point ( death , stroke , reinfa rct ion , need for emergency revascularization with angioplasty or bypass surgery , or recurrent ischemia ) : 13 % versus 24 % , P<.04 . Conclusions This r and omized trial showed that careful use of prophylactic aortic counterpulsation can prevent reocclusion of the infa rct -related artery and improve overall clinical outcome in patients undergoing acute cardiac catheterization during myocardial infa rct ion Background : The benefit of Output:	The high incidence of complications such as moderate and severe bleeding or infection in the control groups has to be attributed to interventions with other LVAD . Available evidence suggests that IABP may have a beneficial effect on some haemodynamic parameters . However , this did not result in survival benefits so there is no convincing r and omised data to support the use of IABP in infa rct -related cardiogenic shock
MS21616	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND OBJECTIVE : Impoverished urban children suffer disproportionately from asthma and underuse preventive asthma medications . The objective of this study was to examine cost-effectiveness ( CE ) of the School-Based Asthma Therapy ( SBAT ) program compared with usual care ( UC ) . METHODS : The analysis was based on the SBAT trial , including 525 children aged 3 to 10 years attending urban preschool or elementary school who were r and omized to either UC or administration of 1 dose of preventive asthma medication at school by the school nurse each school day . The primary outcome was the mean number of symptom-free days ( SFDs ) . The impact of the intervention on medical costs was estimated by using parent-reported child health services utilization data and average national reimbursement rates . We estimated the cost of running the program using wages for program staff . Productivity costs were estimated by using value of parent lost time due to child illness . CE of the SBAT program compared with UC was evaluated based on the incremental CE ratio . RESULTS : The health benefit of the intervention was equal to ∼158 SFD gained per each 30-day period ( P < .05 ) per 100 children . The programmatic expenses summed to an extra $ 4822 per 100 children per month . The net saving due to the intervention ( reduction in medical costs and parental productivity , and improvement in school attendance ) was $ 3240 , result ing in the incremental cost-savings difference of $ 1583 and CE of $ 10 per 1 extra SFD gained . CONCLUSIONS : The SBAT was effective and cost-effective in reducing symptoms in urban children with asthma compared with other existing programs UNLABELLED Teachers and support staff are often called upon to manage asthma at school but may have little knowledge and underst and ing of the condition . The objectives of this study were to develop educational package ( pamphlets ) about asthma , and assess its effectiveness as an educational tool for schools ' staff through evaluation of its impact on the staff 's asthma-related knowledge , attitudes and management practice s on their pupils . A pre-post experimental research design was used in Riyadh city with distribution of self-administered question naires and asthma package to 4 r and omly selected girls schools compounds . Participants were school staff ( n = 297 ) of primary , intermediate and secondary schools . Results showed that only 5.7 % of the staff had received previous training in asthma education . Lack of knowledge and misconceptions about asthma medication were evident among a considerable proportion of the staff specifically for use of antibiotics , steroids , side effect of ventolin , and addicting effect of inhalers . At pretest , only 35 % and 40.1 % of the staff had good level of knowledge and management practice s. At posttest , the corresponding percentages increased significantly to be 83.9 % and 68.6 % respectively . The mean total score of staff 's asthma related-attitudes became more favorable towards asthma education after intervention , it increased significantly from 53.5 to be 55.0 . Total posttest knowledge score was the only predictor of both staff attitudes and management practice s constituting 9.1 % and 10.2 % of their variance . The great majority cited lack of training ( 92 % ) , unavailability school policy ( 86.8 % ) , and shortage of educational re sources ( 88.3 % ) as barriers against asthma education and management in their schools . CONCLUSIONS Most of school staff had poor to fair level of asthma knowledge and management practice s. Such simple educational intervention using pamphlets and demonstration of inhaler use and peaked flow meter was significantly successful in enhancing staff 's asthma-related knowledge , attitudes and management practice s among their pupils . It is very important that training is directed to all staff as pre-service and in-service programs This article describes the evaluation of a comprehensive school-based asthma management program in an inner-city , largely African-American school system . All 54 elementary schools ( combined enrollment 13,247 students ) from a single urban school system participated in this study . Schools were r and omly divided between immediate and delayed intervention programs . The intervention consisted of 3 separate educational programs ( for school faculty/staff , students with asthma , and peers without asthma ) and medical management for the children with asthma ( including an Individual Asthma Action Plan , medications , and peakflow meters ) . Children with asthma were identified using a case detection program and 736 were enrolled into the intervention study . No significant differences were observed in school absences , grade point average , emergency room visits , or hospitalizations between the immediate and delayed intervention groups . Significant increases in knowledge were observed in the immediate intervention group . This study of a school-based asthma management education and medical intervention program did not show any differences between the intervention and control groups on morbidity outcomes . Our experience leads us to believe that such measures are difficult to impact and are not always reliable . Future research ers should be aware of the problems associated with using such measures . In addition , connecting children with a regular source of health care in this population was difficult . More intensive methods of medical management , such as school-based health centers or supervised asthma therapy , might prove more effective in inner-city schools BACKGROUND In Ohio , 14.5 % of 5- to 9-year-olds and 17.3 % of 10- to 17-year-olds have asthma . Moreover , there is concern that these numbers may underestimate the true disease burden . We sought to evaluate variability in asthma rates and respiratory symptoms among central Ohio fourth grade rs as a means to assess potential undiagnosed and undertreated asthma and its determinants . METHODS We recruited 13 central Ohio elementary schools representing a broad range of nonurban setting s and surveyed fourth grade rs to estimate school-level physician-diagnosed asthma ( PDA ) , respiratory morbidity , and home exposures to smoking and pets . We used generalized linear mixed models with r and om intercept for school to examine relationships among exposures , respiratory symptoms , and PDA . RESULTS Across the 13 schools , 94 % of students participated in the survey , and the estimated asthma prevalence rate was 10.2 % ( N = 101 of 987 ) . An additional 41 % reported not having PDA but then went on to report symptoms consistent with asthma potentially suggestive of undiagnosed asthma . Of students with PDA , 21 % reported symptoms suggestive of poorly controlled asthma . High levels of secondh and smoke ( SHS ) exposure were associated both with PDA ( p = .05 ) and with respiratory symptoms ( p < .0001 ) . Students who owned a cat or a bird were more likely to report respiratory symptoms ( p = .02 and p = .04 , respectively ) . CONCLUSIONS We provide evidence that the already high childhood asthma public health burden in central Ohio may be underreported . Schools may be an ideal location to conduct screenings and implement environmental interventions oriented toward SHS and household pets that will yield respiratory morbidity benefits The present study investigated schools as an appropriate context for an intervention design ed to produce clinical and psychological benefits for children with asthma . A total of 193 out of 219 ( 88.1 % ) children with asthma ( aged 7–9 yrs ) from 23 out of 24 ( 95.8 % ) schools completed the study . Intervention schools received a staff asthma-training session , advice on asthma policy , an emergency β2-agonist inhaler with spacer and whole-class asthma workshops . Nonintervention schools received no asthma-related input . Intervention children required less general practitioner-prescribed preventer medication despite no differences in symptom control compared with the nonintervention asthmatic group . Increased peer knowledge of asthma may have mediated improved active quality of life in the intervention group , together with increased self-esteem in young females . Those females not receiving the intervention , but identified as being asthmatic within the classroom , and thus possibly stigmatised , reported decreased self-esteem . Lower self-esteem in young males was associated with pet ownership . No change was found in staff knowledge , the establishment of asthma policies or school absences which were low even before intervention . In conclusion , a whole-school intervention can improve the health of children with asthma when followed with support for all children but effects are likely to be modified by sex and the home environment Objectives . Because children spend a significant proportion of their day in school , pediatric emergencies such as the exacerbation of medical conditions , behavioral crises , and accidental/intentional injuries are likely to occur . Recently , both the American Academy of Pediatrics and the American Heart Association have published guidelines stressing the need for school leaders to establish emergency-response plans to deal with life-threatening medical emergencies in children . The goals include developing an efficient and effective campus-wide communication system for each school with local emergency medical services ( EMS ) ; establishing and practicing a medical emergency-response plan ( MERP ) involving school nurses , physicians , athletic trainers , and the EMS system ; identifying students at risk for life-threatening emergencies and ensuring the presence of individual emergency care plans ; training staff and students in first aid and cardiopulmonary resuscitation ( CPR ) ; equipping the school for potential life-threatening emergencies ; and implementing lay rescuer automated external defibrillator ( AED ) programs . The objective of this study was to use published guidelines by the American Academy of Pediatrics and the American Heart Association to examine the preparedness of schools to respond to pediatric emergencies , including those involving children with special care needs , and potential mass disasters . Methods . A 2-part question naire was mailed to 1000 r and omly selected members of the National Association of School Nurses . The first part included 20 questions focusing on : ( 1 ) the clinical background of the school nurse ( highest level of education , years practicing as a school health provider , CPR training ) ; ( 2 ) demographic features of the school ( student attendance , grade s represented , inner-city or rural/suburban setting , private or public funding , presence of children with special needs ) ; ( 3 ) self-reported frequency of medical and psychiatric emergencies ( most common reported school emergencies encountered over the past school year , weekly number of visits to school nurses , annual number of “ life-threatening ” emergencies requiring activation of EMS ) ; and ( 4 ) the preparedness of schools to manage life-threatening emergencies ( presence of an MERP , presence of emergency care plans for asthmatics , diabetics , and children with special needs , presence of a school nurse during all school hours , CPR training of staff and students , availability of athletic trainers during all athletic events , presence of an MERP for potential mass disasters ) . The second part included 10 clinical scenarios measuring the availability of emergency equipment and the confidence level of the school nurse to manage potential life-threatening emergencies . Results . Of the 675 question naires returned , 573 were eligible for analysis . A majority of responses were from registered nurses who have been practicing for > 5 years in a rural or suburban setting . The most common reported school emergencies were extremity sprains and shortness of breath . Sixty-eight percent ( 391 of 573 [ 95 % confidence interval ( CI ) : 64–72 % ] ) of school nurses have managed a life-threatening emergency requiring EMS activation during the past school year . Eighty-six percent ( 95 % CI : 84–90 % ) of schools have an MERP , although 35 % ( 95 % CI : 31–39 % ) of schools do not practice the plan . Thirteen percent ( 95 % CI : 10–16 % ) of schools do not identify authorized personnel to make emergency medical decisions . When stratified by mean student attendance , school setting , and funding classification , schools with and without an MERP did not differ significantly . Of the 205 schools that do not have a school nurse present on campus during all school hours , 17 % ( 95 % CI : 12–23 % ) do not have an MERP , 17 % ( 95 % CI : 12–23 % ) do not identify an authorized person to make medical decisions when faced with a life-threatening emergency , and 72 % ( 95 % CI : 65–78 % ) do not have an effective campus-wide communication system . CPR training is offered to 76 % ( 95 % CI : 70–81 % ) of the teachers , 68 % ( 95 % CI : 61–74 % ) of the administrative staff , and 28 % ( 95 % CI : 22–35 % ) of the students . School nurses reported the availability of a bronchodilator meter-dosed inhaler ( 78 % [ 95 % CI : 74–81 % ] ) , AED ( 32 % [ 95 % CI : 28–36 % ] ) , and epinephrine autoinjector ( 76 % [ 95 % CI : 68–79 % ] ) in their school . When stratified by inner-city and rural/suburban school setting , the availability of emergency equipment did not differ significantly except for the availability of an oxygen source , which was higher in rural/suburban schools ( 15 % vs 5 % ) . School-nurse responders self-reported more confidence in managing respiratory distress , airway obstruction , profuse bleeding/extremity fracture , anaphylaxis , and shock in a diabetic child and comparatively less confidence in managing cardiac arrest , overdose , seizure , heat illness , and head injury . When analyzing schools with at least 1 child with special care needs , 90 % ( 95 % CI : 86–93 % ) have an MERP , 64 % ( 95 % CI : 58–69 % ) have a nurse available during all school hours , and 32 % ( Output:	Data for symptom days , night-time awakenings , restricted activities of daily living and school absences were skewed or could not be analysed ; some mean scores were better in the trained group , but most differences between groups were small and did not persist to 24 months . Schools that received asthma education were more adherent to asthma policies , and staff were better prepared ; more schools that had received staff asthma training had written asthma policies compared with control schools , more intervention schools showed improvement in measures taken to prevent or manage exercise-induced asthma attacks and more staff at intervention schools reported that they felt able to administer salbutamol via a spacer . Asthma education for school staff increases asthma knowledge and preparedness , but studies vary and all available evidence is of low quality . Studies have not yet captured whether this improvement in knowledge has led to appreciable benefits over the short term or the longer term for the safety and health of children with asthma in school . R and omised evidence does not contribute to our knowledge of content or attributes of interventions that lead to the best outcomes , or of re sources required for successful implementation . This applies to both r and omised and non-r and omised studies , although the latter may be better placed to observe important clinical outcomes such as exacerbations and mortality in the longer term
MS21617	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Background Systemic endothelial dysfunction has been identified as one of the main events in preeclampsia ( PE ) . A nonhealthy vascular endothelium can be pointed out as the pathophysiological explanation of the clinical manifestations and complications of PE . Once normal pregnancy is characterized by a constant increase in endothelial function , a follow-up of this physiological event could be used as an early marker or a prediction tool to predict PE . Objectives To perform a longitudinal assessment of endothelial function , using an ultrasound study of brachial artery flow Flow-mediated dilation ( FMD ) , in normotensive and preeclamptic pregnancies , to evaluate the difference of FMD values along the second trimester of pregnancy to predict PE . Patients and methods In a prospect i ve cohort study , 91 pregnant women with a high risk of developing PE were subjected to FMD of the brachial artery . The difference in the FMD values , between 16 + 0 and 19 + 6 and 24 + 0 and 27 + 6 weeks of gestation were compared , taking PE development into consideration . Receiver operator characteristics ( ROC ) curves were created to determine the sensibility and specificity of FMD difference to predict PE . Results A total of 19 patients developed PE and the other 72 women remained normotensive until 1 week after delivery . When considering a cut off of + 2.50 % , FMD difference , between the two evaluations , sensitivity for PE prediction was 87.5 % for early onset PE and 95.5 % for late PE . Conclusion The difference of FMD values between the second trimester of pregnancy can be used for PE prediction for both , early and late forms of PE Background Preterm preeclampsia is an important cause of maternal and perinatal death and complications . It is uncertain whether the intake of low‐dose aspirin during pregnancy reduces the risk of preterm preeclampsia . Methods In this multicenter , double‐blind , placebo‐controlled trial , we r and omly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin , at a dose of 150 mg per day , or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation . The primary outcome was delivery with preeclampsia before 37 weeks of gestation . The analysis was performed according to the intention‐to‐treat principle . Results A total of 152 women withdrew consent during the trial , and 4 were lost to follow up , which left 798 participants in the aspirin group and 822 in the placebo group . Preterm preeclampsia occurred in 13 participants ( 1.6 % ) in the aspirin group , as compared with 35 ( 4.3 % ) in the placebo group ( odds ratio in the aspirin group , 0.38 ; 95 % confidence interval , 0.20 to 0.74 ; P=0.004 ) . Results were material ly unchanged in a sensitivity analysis that took into account participants who had withdrawn or were lost to follow‐up . Adherence was good , with a reported intake of 85 % or more of the required number of tablets in 79.9 % of the participants . There were no significant between‐group differences in the incidence of neonatal adverse outcomes or other adverse events . Conclusions Treatment with low‐dose aspirin in women at high risk for preterm preeclampsia result ed in a lower incidence of this diagnosis than placebo . ( Funded by the European Union Seventh Framework Program and the Fetal Medicine Foundation ; EudraCT number , 2013‐003778‐29 ; Current Controlled Trials number , IS RCT N13633058 . This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS  Boston University Patricia Cortes  Harvard University Claudia Goldin  Swarthmore College Jennifer Background — Preeclampsia is a life-threatening pregnancy syndrome of uncertain origin . To eluci date the pathogenesis , we evaluated the temporal relationships between changes in vascular function and circulating biomarkers of angiogenic activity before and after the onset of preeclampsia and gestational hypertension . Methods and Results — Maternal mean arterial pressure , uterine artery pulsatility index , brachial artery flow-mediated dilatation , and serum concentrations of placental growth factor ( PlGF ) , soluble fms-like tyrosine kinase 1 ( sFlt-1 ) , and soluble endoglin were prospect ively measured in 159 women from 10 weeks gestation until 12 weeks postpartum . At 10 to 17 weeks , women who developed preterm preeclampsia had lower serum PlGF ( P=0.003 ) , higher soluble endoglin ( P=0.006 ) , and higher sFlt-1:PlGF ratio ( P=0.005 ) compared with women who later developed term preeclampsia , gestational hypertension , or normotensive pregnancy . At 10 to 17 weeks , mean arterial pressure inversely correlated with serum PlGF ( r=−0.19 , P=0.02 ) ; at 18 to 25 weeks , with soluble endoglin ( r=0.18 , P=0.02 ) ; and at 26 to 33 weeks , with sFlt-1 ( r=0.28 , P<0.001 ) . At 23 to 25 weeks , uterine artery pulsatility index correlated with serum soluble endoglin ( r=0.19 , P=0.02 ) and sFlt-1 levels ( r=0.17 , P=0.03 ) . Flow-mediated dilatation was higher during a pregnancy with gestational hypertension compared with preeclampsia ( P=0.001 ) . Twelve weeks postpartum , serum PlGF was higher in women who had a hypertensive pregnancy compared with a normotensive pregnancy ( P<0.001 ) . Conclusions — These observations support a role for placenta-derived angiogenic biomarkers in the control of maternal vascular resistance of preeclampsia . Gestational hypertension develops differently , with a hyperdynamic circulation and angiogenic biomarker profile similar to normotensive pregnancy . Larger studies of unselected women are needed to ascertain whether measures of these angiogenic biomarkers assist with the prediction and prognosis of preeclampsia and whether postpartum measures of serum PlGF have a role in predicting future cardiovascular disease Background — Coronary artery calcium ( CAC ) has been demonstrated to be associated with the risk of coronary heart disease . The Multi-Ethnic Study of Atherosclerosis ( MESA ) provides a unique opportunity to examine the distribution of CAC on the basis of age , gender , and race/ethnicity in a cohort free of clinical cardiovascular disease and treated diabetes . Methods and Results — MESA is a prospect i ve cohort study design ed to investigate sub clinical cardiovascular disease in a multiethnic cohort free of clinical cardiovascular disease . The percentiles of the CAC distribution were estimated with nonparametric techniques . Treated diabetics were excluded from analysis . There were 6110 included in the analysis , with 53 % female and an average age of 62 years . Men had greater calcium levels than women , and calcium amount and prevalence were steadily higher with increasing age . There were significant differences in calcium by race , and these associations differed across age and gender . For women , whites had the highest percentiles and Hispanics generally had the lowest ; in the oldest age group , however , Chinese women had the lowest values . Overall , Chinese and black women were intermediate , with their order dependent on age . For men , whites consistently had the highest percentiles , and Hispanics had the second highest . Blacks were lowest at the younger ages , and Chinese were lowest at the older ages . At the MESA public website ( http://www.mesa-nhlbi.org ) , an interactive form allows one to enter an age , gender , race/ethnicity , and CAC score to obtain a corresponding estimated percentile . Conclusions — The information provided here can be used to examine whether a patient has a high CAC score relative to others with the same age , gender , and race/ethnicity who do not have clinical cardiovascular disease or treated diabetes Preeclampsia is a leading cause of maternal morbidity and mortality . The degree of maternal cardiovascular dysfunction that precedes the onset of preeclampsia is largely unknown . This prospect i ve cohort study aim ed to characterize differences in vivo in retinal microvascular caliber and blood pressure throughout pregnancy in relation to preeclampsia development . Women were recruited from Royal Prince Alfred Hospital , Sydney , Australia , of which 92 women were included in the study . Retinal images and blood pressures were collected at 13 , 19 , 29 , and 38 weeks of gestation . Retinal vessels were analyzed as the central retinal arteriolar equivalent corrected for mean arterial blood pressure and the central retinal venular equivalent corrected for mean arterial blood pressure , using generalized linear models adjusted for age and body mass index . The preeclampsia group were significantly older ( P=0.002 ) and had a significantly higher mean body mass index ( P=0.005 ) . The central retinal arteriolar equivalent corrected for mean arterial blood pressure was significantly reduced at 13 ( P=0.03 ) , 19 ( P=0.007 ) , and 38 ( P=0.03 ) weeks of gestation in the preeclampsia group . The central retinal venular equivalent corrected for mean arterial blood pressure was also significantly lower at 13 ( P=0.04 ) and 19 ( P=0.001 ) weeks of gestation in the women who progressed to preeclampsia . This study directly documents increased peripheral resistance in vivo , observed as the combination of constricted retinal arterioles or venules and elevated blood pressure , in women who later developed preeclampsia . This difference preceded the clinical signs of preeclampsia OBJECTIVES The purpose of this study was to determine the prognostic accuracy of electron beam computed tomographic ( CT ) scanning of the coronary arteries and the relationship of coronary calcification to st and ard coronary disease risk factors and C-reactive protein ( CRP ) in the prediction of atherosclerotic cardiovascular disease ( ASCVD ) events in apparently healthy middle-age persons . BACKGROUND As a screening test for coronary artery disease ( CAD ) , electron beam CT scanning remains controversial . METHODS In a prospect i ve , population -based study , 4,903 asymptomatic persons age 50 to 70 years underwent electron beam CT scanning of the coronary arteries . RESULTS At 4.3 years , follow-up was available in 4,613 participants ( 94 % ) , and 119 had sustained at least one ASCVD event . Subjects with ASCVD events had higher baseline coronary calcium scores ( median [ interquartile range ] , Agatston method ) than those without events : 384 ( 127 , 800 ) versus 10 ( 0 , 86 ) ( p < 0.0001 ) . For coronary calcium score threshold > or = 100 versus < 100 , relative risk ( 95 % confidence interval ) was 9.6 ( 6.7 to 13.9 ) for all ASCVD events , 11.1 ( 7.3 to 16.7 ) for all CAD events , and 9.2 ( 4.9 to 17.3 ) for non-fatal myocardial infa rct ion and death . The coronary calcium score predicted CAD events independently of st and ard risk factors and CRP ( p = 0.004 ) , was superior to the Framingham risk index in the prediction of events ( area under the receiver-operating characteristic curve of 0.79 + /- 0.03 vs. 0.69 + /- 0.03 , p = 0.0006 ) , and enhanced stratification of those falling into the Framingham categories of low , intermediate , and high risk ( p < 0.0001 ) . CONCLUSIONS The electron beam CT coronary calcium score predicts CAD events independent of st and ard risk factors , more accurately than st and ard risk factors and CRP , and refines Framingham risk stratification OBJECTIVES To assess the evolution of the soluble fms-like tyrosine kinase-1 ( sFlt-1 ) to placental growth factor ( PlGF ) ratio in women with suspected or confirmed pre-eclampsia ( PE ) , and to investigate the changes in sFlt-1 and PlGF levels in pre-eclamptic women after delivery . METHODS This was an exploratory study in which secondary analysis was performed on a prospect i ve cohort study that enrolled women with a singleton pregnancy and suspected or confirmed PE from 18 weeks ' gestation , carried out between December 2013 and April 2016 at the Department of Obstetrics of the Erasmus Medical Center in Rotterdam . sFlt Output:	Accelerated coronary calcification and plaque deposition was identified , with greater rates of increased calcium scores and sub clinical coronary artery disease shown by CTCA in women with a history of pre-eclampsia at 30 years postpartum . The evidence was less conclusive for the persistence of long-term endothelial dysfunction .
MS21618	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Caffeine , an adenosine receptor antagonist , has shown to improve performance in normal ambient temperature , presumably via an effect on dopaminergic neurotransmission through the antagonism of adenosine receptors . However , there is very limited evidence from studies that administered caffeine and examined its effects on exercise in the heat . Therefore , we wanted to study the effects of caffeine on performance and thermoregulation in high ambient temperature . Eight healthy trained male cyclists completed two experimental trials ( in 30 ° C ) in a double-blind-r and omized crossover design . Subjects ingested either placebo ( 6 mg/kg ) or caffeine ( 6 mg/kg ) 1 h prior to exercise . Subjects cycled for 60 min at 55 % Wmax , immediately followed by a time trial to measure performance . The significance level was set at p < 0.05 . Caffeine did not change performance ( p = 0.462 ) . Rectal temperature was significantly elevated after caffeine administration ( p < 0.036 ) . Caffeine significantly increased B-endorphin plasma concentrations at the end of the time trial ( p = 0.032 ) . The present study showed no ergogenic effect of caffeine when administered 1 h before exercise in 30 ° C . This confirms results from a previous study that examined the effects of caffeine administration on a short ( 15 min ) time trial in 40 ° C . However , caffeine increased core temperature during exercise . Presumably , the rate of increase in core temperature may have counteracted the ergogenic effects of caffeine . However , other factors such as interindividual differences in response to caffeine and changes in neurotransmitter concentrations might also be responsible for the lack of performance improvement of caffeine in high ambient temperature This study compared the effects of a single and divided dose of caffeine on endurance performance and on postexercise urinary caffeine and plasma paraxanthine concentrations . Nine male cyclists and triathletes cycled for 90 min at 68 % of maximal oxygen uptake , followed by a self-paced time trial ( work equivalent to 80 % of maximal oxygen uptake workload over 30 min ) with three r and omized , balanced , and double-blind interventions : 1 ) placebo 60 min before and 45 min into exercise ( PP ) ; 2 ) single caffeine dose ( 6 mg/kg ) 60 min before exercise and placebo 45 min into exercise ( CP ) ; and 3 ) divided caffeine dose ( 3 mg/kg ) 60 min before and 45 min into exercise ( CC ) . Time trial performance was unchanged with caffeine ingestion ( P = 0.08 ) , but it tended to be faster in the caffeine trials ( CP : 24.2 min and CC : 23.4 min ) compared with placebo ( PP : 28.3 min ) . Postexercise urinary caffeine concentration was significantly lower in CC ( 3.8 micro g/ml ) compared with CP ( 6.8 micro g/ml ) . Plasma paraxanthine increased in a dose-dependent fashion and did not peak during exercise . In conclusion , dividing a caffeine dose provides no ergogenic effect over a bolus dose but reduces postexercise urinary concentration The power of placebos has long been recognized for improving numerous medical conditions such as Parkinson 's disease ( PD ) . Little is known , however , about the mechanism underlying the placebo effect . Using the ability of endogenous dopamine to compete for [11C]raclopride binding as measured by positron emission tomography , we provide in vivo evidence for substantial release of endogenous dopamine in the striatum of PD patients in response to placebo . Our findings indicate that the placebo effect in PD is powerful and is mediated through activation of the damaged nigrostriatal dopamine system Purpose Many studies have examined the effect of caffeine on exercise performance , but findings have not always been consistent . The objective of this study was to determine whether variation in the CYP1A2 gene , which affects caffeine metabolism , modifies the ergogenic effects of caffeine in a 10-km cycling time trial . Methods Competitive male athletes ( n = 101 ; age = 25 ± 4 yr ) completed the time trial under three conditions : 0 , 2 , or 4 mg of caffeine per kilogram body mass , using a split-plot r and omized , double-blinded , placebo-controlled design . DNA was isolated from saliva and genotyped for the −163A > C polymorphism in the CYP1A2 gene ( rs762551 ) . Results Overall , 4 mg·kg−1 caffeine decreased cycling time by 3 % ( mean ± SEM ) versus placebo ( 17.6 ± 0.1 vs 18.1 ± 0.1 min , P = 0.01 ) . However , a significant ( P < 0.0001 ) caffeine – gene interaction was observed . Among those with the AA genotype , cycling time decreased by 4.8 % at 2 mg·kg−1 ( 17.0 ± 0.3 vs 17.8 ± 0.4 min , P = 0.0005 ) and by 6.8 % at 4 mg·kg−1 ( 16.6 ± 0.3 vs 17.8 ± 0.4 min , P < 0.0001 ) . In those with the CC genotype , 4 mg·kg−1 increased cycling time by 13.7 % versus placebo ( 20.8 ± 0.8 vs 18.3 ± 0.5 min , P = 0.04 ) . No effects were observed among those with the AC genotype . Conclusion Our findings show that both 2 and 4 mg·kg−1 caffeine improve 10-km cycling time , but only in those with the AA genotype . Caffeine had no effect in those with the AC genotype and diminished performance at 4 mg·kg−1 in those with the CC genotype . CYP1A2 genotype should be considered when deciding whether an athlete should use caffeine for enhancing endurance performance Aim The purpose of this study was to examine the effect of CYP1A2 -163C > A polymorphism on the ergogenic effects of caffeine supplementation during a resistance exercise ( RE ) session . Methods In a r and omized , double-blind , placebo (PL)-controlled , crossover study , 30 resistance-trained men took part in two RE sessions ( three sets to failure at 85 % of one repetition maximum , 2-min rest between sets ) , including bench press ( BP ) , leg press ( LP ) , seated cable row , and shoulder press ( SP ) following caffeine ( CAF ) ( 6 mg kg−1 ) or PL ( 6 mg kg−1 of maltodextrin ) ingestion 1 h prior to the trial . The number of repetitions was recorded after each set , along with calculation of total number of repetitions for each exercise . Genomic DNA was isolated from the whole blood sample s for analyzing the CYP1A2 -163C > A polymorphism through amplification refractory mutation system – polymerase chain reaction ( ARMS – PCR ) . Subjects were classified as either AA ( n = 14 ) or AC/CC genotypes ( n = 16 ) . Results The two-way ANOVA with repeated measures revealed differences between AAs and AC/CCs under CAF conditions for repetitions performed in sets 1 , 2 , and 3 of BP ( F(1 , 28 ) = 14.84 , P = 0.001 , ƞ2 = 0.34 ) , LP ( F(1 , 28 ) = 8.92 , P = 0.006 , ƞ2 = 0.24 ) , SR ( F(1 , 28 ) = 17.38 , P = 0.0001 , ƞ2 = 0.38 ) , and SP ( F(1 , 28 ) = 3.76 , P = 0.063 , ƞ2 = 0.11 ) . CAF also increased the total number of repetitions performed for all three sets in AAs versus AC/CCs for BP ( F(1 , 28 ) = 8.72 , P = 0.006 , ƞ2 = 0.23 ) , LP ( F(1 , 28 ) = 4.67 , P = 0.03 , ƞ2 = 0.14 ) , SR ( F(1 , 28 ) = 5.54 , P = 0.02 , ƞ2 = 0.16 ) , and SP ( F(1 , 28 ) = 3.89 , P = 0.058 , ƞ2 = 0.12 ) in athletes who were homozygous carriers of the A allele , compared to the C allele carriers . Therefore , AA homozygotes were able to carry out a greater total volume of RE work under CAF but not PL conditions , compared to the C allele carriers . Conclusion In conclusion , acute ingestion of CAF significantly enhanced RE performance in resistance-trained men who were homozygous for the A allele , but not for C allele carriers . Further studies are needed to replicate the potential role of the CYP1A2 -163C > A polymorphism on the ergogenic effects of CAF in other modes of exercise and in other population PURPOSE To determine the effects of ingesting caffeine ( CAFF ) and sodium bicarbonate ( SB ) , taken individually and simultaneously , on 3-km cycling time-trial ( TT ) performance . METHOD Ten well-trained cyclists , age 24.2 ± 5.4 yr , participated in this acute-treatment , double-blind , crossover study that involved four 3-km cycling TTs performed on separate days . Before each TT , participants ingested either 3 mg/kg body mass ( BM ) of CAFF , 0.3 g · kg⁻¹ · BM⁻¹ of SB , a combination of the two ( CAFF+SB ) , or a placebo ( PLAC ) . They completed each 3-km TT on a laboratory-based cycle ergometer , during which physiological , perceptual , and performance measurements were determined . For statistical analysis , the minimal worthwhile difference was considered ~1 % based on previous research . RESULTS Pretrial pH and HCO₃ were higher in SB and CAFF+SB than in the CAFF and PLAC trials . Differences across treatments for perceived exertion and gastric discomfort were mostly unclear . Compared with PLAC , mean power output during the 3-km TT was higher in CAFF , SB , and CAFF+SB trials ( 2.4 % , 2.6 % , 2.7 % respectively ) , result ing in faster performance times ( -0.9 , -1.2 , -1.2 % respectively ) . Effect sizes for all trials were small ( 0.21 - 0.24 ) . CONCLUSIONS When ingested individually , both CAFF and SB enhance high-intensity cycling TT performance in trained cyclists . However , the ergogenic effect of these 2 popular supplements was not additive , bringing into question the efficacy of coingesting the 2 supplements before short- duration high-intensity exercise . In this study there were no negative effects of combining CAFF and SB , 2 relatively inexpensive and safe supplements Hudson , GM , Green , JM , Bishop , PA , and Richardson , MT . Effects of caffeine and aspirin on light resistance training performance , RPE , and pain perception . J Strength Cond Res 22(6 ) : 1950 - 1957 , 2008-This study compared independent effects of caffeine and aspirin on muscular endurance ( repetitions ) , heart rate ( HR ) , perceived exertion ( RPE ) , and perceived pain index ( PPI ) during light resistance training bouts performed to volitional failure . It was hypothesized that the hypoalgesic properties of these ergogenic aids would decrease pain perception and potentially result in enhanced performance . College-aged men ( n = 15 ) participated in a within-subjects , double-blind study with three independent , counterbalanced sessions wherein aspirin ( 10 mg·kg−1 ) , caffeine ( 6 mg·kg−1 ) , or matched placebo were ingested 1 hour before exercise , and RPE , HR , PPI , and repetitions ( per set and total per exercise ) were recorded at 100 % of individual , predetermined , 12-repetition maximum for leg extensions ( LE ) and seated arm curls ( AC ) . Repeated- measures analyses of variance were used for between-trial comparisons . Caffeine result ed in significantly greater ( p < 0.05 ) HR ( LE and AC ) , total repetitions ( LE ) , and repetitions in set 1 ( LE and AC ) compared with aspirin and placebo . Aspirin result ed in significantly higher PPI in set 1 ( LE ) . In LE , 47 % of participants ' performance exceeded the predetermined effect size ( ≥ 5 repetitions ) for total repetitions , with 53 % exceeding the effect size ( ≥ 2 repetitions ) for repetitions in set 1 with caffeine ( vs. placebo ) . In AC , 53 % ( total repetitions ) and 47 % ( set 1 repetitions ) of participants exceeded effect sizes with caffeine ( vs. placebo ) , with only 13 % experiencing decrements in performance ( total repetitions ) . Aspirin also produced a higher PPI and RPE overall and in set 1 ( vs. placebo ) . This study demonstrates that caffeine significantly enhanced resistance training performance in LE and AC , whereas aspirin Output:	Firstly , previous experience/habituation has been suggested as a factor that provides learning and information about the treatment [ 11 ] , thereby driving participants ’ expectations about caffeine ’s ergogenic effects .
MS21619	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Aim To investigate the association between dry eye symptoms and depression in an adult population . Methods In this population -based cross-sectional study , a r and om sample of 1957 subjects from the Beijing Eye Study was examined for dry eye disease ( DED ) in 2006 . All patients completed an interviewer-assisted question naire on dry eye symptoms and underwent measurement of tear break-up time ( TBUT ) , slit-lamp evaluation of corneal staining and meibomian gl and dysfunction ( MGD ) , and the Schirmer test . In 2011 , 1456 subjects from this sample were evaluated for depression using a depression scale . The association between depression symptoms and dry eye clinical tests was evaluated . Results Definite depression was more prevalent in patients with DED than in subjects without DED ( 13.7±0.4 % vs 8.6±0.3 % , p=0.02 ) . The depression score was correlated with dry eye symptoms ( correlation coefficient r=0.07 ; p=0.013 ) but not with TBUT ( p=0.18 ) , the Schirmer test ( p=0.37 ) , corneal staining ( p=0.30 ) and MGD evaluation ( p=0.93 ) . In multivariate regression analysis , the risk of definite depression remained significantly associated with dry eye symptoms ( p=0.028 ) after adjusting for lower cognitive status ( p=0.01 ) , rural region of habitation ( p=0.023 ) and lower body weight ( p=0.05 ) . Conclusions In an older population from Beijing , depression was associated with DED and in particular with dry eye symptoms OBJECTIVE To investigate the significant determinants of health-related quality of life ( HRQOL ) and the association of the EULAR Sjögren 's syndrome patient reported index ( ESSPRI ) with clinical parameters including HRQOL in Korean patients with primary Sjögren 's syndrome ( pSS ) compared with non-SS sicca patients . METHODS We prospect ively analysed 104 pSS and 42 non-SS sicca patients . Clinical data including Short Form 36 ( SF-36 ) scores , self- assessment s for symptoms and ESSPRI were cross-sectionally collected . RESULTS Although most self- assessment s and HRQOL statuses were comparable , different association patterns between HRQOL and symptoms were observed in pSS and non-SS sicca patients . pSS patients with low HRQOL had significantly higher ESSPRI scores [ P = 7.6 × 10(-6 ) for physical component summary ( PCS ) subgroups and P = 0.0015 for mental component summary ( MCS ) subgroups ] and ESSPRI scores showed a significant association with all SF-36 scales in pSS patients ( all P ≤ 0.0020 ) . Moreover , in multivariate linear regression analyses , ESSPRI ( P = 0.035 ) and depression ( P = 4.1 × 10(-14 ) ) were significantly correlated with the PCS and the MCS , respectively . However , in the non-SS sicca group , xerostomia inventory ( XI ) scores were higher in the low PCS subgroup ( P = 0.031 ) and this correlated with five SF-36 scales ( all P ≤ 0.046 ) . XI scores ( P = 0.0039 ) and anxiety ( P = 7.9 × 10(-10 ) ) were the main determinants of the PCS and MCS , respectively . CONCLUSION HRQOL levels were differentially associated with clinical facets in pSS and non-SS sicca patients , although the groups had similar clinical symptoms and HRQOL reduction . Because depression and ESSPRI are major determinants of HRQOL in Korean pSS patients , ESSPRI is suggested to be disease-specific for pSS Objective . Although multiple diseases associated with primary Sjögren ’s syndrome ( pSS ) have been reported , reliable data regarding the prevalence of specific medical comorbidities among patients with pSS remain sparse . We investigated the prevalence and risk for a broad spectrum of medical conditions among patients with pSS in Taiwan . Methods . A total of 1974 patients with pSS were eligible for inclusion in the study group . We r and omly selected 9870 enrollees matched with the study subjects , using the Taiwan National Health Insurance Research Data set for 2006 and 2007 , inclusive . Conditional logistic regression analyses conditioned on sex , age , monthly income , and level of urbanization of the patient ’s community were used to calculate the odds ratios ( OR ) of various comorbid conditions . Results . Pearson chi-square tests revealed that patients with pSS had significantly higher prevalence of hyperlipidemia , cardiac arrhythmias , headaches , migraines , fibromyalgia ( FM ) , asthma , pulmonary circulation disorders , hypothyroidism , liver disease , peptic ulcers , hepatitis B , deficiency anemias , depression , and psychoses . Conditional regression analyses showed that , compared to patients without the condition , patients with pSS were more likely to have hyperlipidemia ( OR 1.42 ) , cardiac arrhythmias ( OR 1.32 ) , headaches ( OR 1.47 ) , migraines ( OR 1.86 ) , FM ( OR 1.71 ) , asthma ( OR 1.54 ) , pulmonary circulation disorders ( OR 1.42 ) , hypothyroidism ( OR 2.37 ) , liver disease ( OR 1.89 ) , peptic ulcers ( OR 1.88 ) , hepatitis B ( OR 2.34 ) , deficiency anemias ( OR 1.33 ) , depression ( OR 2.57 ) , and psychoses ( OR 2.15 ) . Conclusion . The prevalence of several comorbidities was increased among the patients with pSS . Our study provides epidemiological data for comorbidities among pSS patients in an ethnic Chinese population OBJECTIVE Corneal and ocular wavefront aberrations were recorded together with clinical examination results and patient-reported vision-related quality -of-life evaluation results to define the relevance of dynamic optical analysis of the eye in dry eye disease ( DED ) . DESIGN Prospect i ve and comparative clinical study . PARTICIPANTS Forty DED patients and 40 age- and gender-matched control subjects . METHODS Serial measurements of ocular and corneal higher-order aberrations ( HOAs ) after blink were performed for 10 seconds using the KR-1 aberrometer ( Topcon , Clichy , France ) . Vision-related health-targeted quality of life was evaluated using the Ocular Surface Disease Index ( OSDI ) question naire . The clinical examination included tear film assessment ( tear film break-up time and Schirmer I test ) , ocular surface damage assessment with the Oxford and van Bijsterveld indexes , and Meibomian dysfunction grading . Tear osmolarity also was measured . MAIN OUTCOME MEASURES The time course of HOAs and modulation transfer function ( MTF ) was compared between groups and was analyzed in comparison with the OSDI and clinical data in DED patients . RESULTS The root mean square of ocular and corneal total HOAs , particularly third-order aberrations , significantly increased over the 10-second period in DED patients , whereas no change occurred in controls . Analysis of MTF revealed progressive degradation of ocular optical quality result ing from loss of contrast at intermediate and high spatial frequencies in DED patients compared with controls . The progression index for corneal HOAs was correlated with the subjective index of patient-reported visual outcomes and with objective clinical findings of tear film and ocular surface damage . CONCLUSIONS Objective measurement of the time course of HOAs may constitute a new single instrument to evaluate and manage patients with DED because it reliably reflects the completeness of the disease PURPOSE A population -based cross-sectional study to investigate the association between depression and dry eye disease ( DED ) in a community-dwelling elderly population . METHODS The subjects were 657 Korean elders ≥ 65 years of age r and omly selected from an official household registration data base in Yongin , Korea . DED symptoms were assessed using the six-item Dry Eye Question naire . DED signs were evaluated using the Schirmer test , fluorescein stain score , tear film break-up time ( BUT ) . Depression was assessed using the Korean version of the Short Geriatric Depression Scale ( SGDS-K ) . The association between DED and depression was evaluated using logistic linear analyses . RESULTS The SGDS-K score correlated with the number of positive responses in the Dry Eye Question naire ( r = 0.229 , P < 0.001 ) , but not with tear film break-up time ( r = 0.041 , P = 0.139 ) or Schirmer test score ( r = 0.048 , P = 0.642 ) . In the binary logistic regression model , female sex ( P = 0.014 ) , residence in urban areas ( P < 0.001 ) , depression ( P < 0.001 ) , and Schirmer score of ≤ 5 mm ( P = 0.035 ) were associated with the risk of DED . Depression was associated with the risk of DED ( P < 0.001 ) in the patients with Schirmer score > 5 mm but not in those with Schirmer score ≤ 5 mm ( P = 0.290 ) . CONCLUSIONS Depression was associated with DED symptoms in subjects with normal or mildly reduced tear production OBJECTIVE To compare pain , fatigue , and sicca symptoms ; quality of life ; and psychological status between patients with primary Sjögren 's syndrome ( SS ) and those with sicca symptoms but no autoimmune features ( sicca asthenia polyalgia syndrome [ SAPS ] ) , and to determine whether a psychological pattern can be detected in patients with SAPS , which could suggest psychological distress as the cause . METHODS This cross-sectional , prospect i ve study included 111 patients with primary SS according to the American-European Consensus Group criteria and 65 SAPS patients with no focus on lip biopsy and no anti-SSA/SSB antibodies . Pain , fatigue , and sicca symptoms were assessed using visual analog scales ; quality of life was assessed using the Short Form 36 ( SF-36 ) ; and psychological distress by the Symptom Checklist-90-Revised ( SCL-90-R ) question naire . RESULTS No difference was observed between primary SS and SAPS patients for pain , fatigue , sicca symptoms , quality of life , and psychological status . Fatigue and pain , but not dryness , were correlated with both quality of life and psychological distress in both groups . For primary SS patients , physical and mental composite scores on the SF-36 correlated well with global severity index ( GSI ) scores of the SCL-90-R ( r = -0.29 , P = 0.006 and r = -0.61 , P < 0.0001 , respectively ) . CONCLUSION Patients with primary SS and SAPS do not differ in quality of life or psychological status . Although both diseases probably have a different origin , they may require the same psychological support or psychiatric care . The strong correlation between the composite physical and mental scores of the SF-36 and the GSI scores of the SCL-90-R in primary SS patients emphasizes the importance of the psychological dimension in results of the SF-36 Output:	Subgroup analyses revealed that the prevalence and severity of depression are greatest in primary Sjogren ’s syndrome patients . Conclusion Depression and anxiety are more prevalent in DED patients than in controls . Among patients with DED , those suffering from primary Sjogren 's syndrome have higher prevalence and severity of depression
MS21620	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In this prospect i ve study of 45 patients , we tested the hypothesis that markedly elevated levels of plasma von Willebr and antigen ( vWf-Ag ) a marker of endothelial cell injury , might predict the development of acute lung injury in patients with nonpulmonary sepsis syndrome . Acute lung injury was quantified on a four-point scoring system . At the time of entry into the study , none of the 45 patients had evidence of lung injury . Subsequently , 15 patients developed lung injury and 30 patients did not develop lung injury . The mean plasma vWf-Ag level was markedly elevated in the 15 patients who developed lung injury compared with the 30 patients who did not develop lung injury ( 588 + /- 204 vs. 338 + /- 196 , percentage of control , P less than 0.01 ) . Furthermore , a plasma vWf-Ag level greater than or equal to 450 was 87 % sensitive and 77 % specific for predicting the development of acute lung injury in the setting of nonpulmonary sepsis . In addition , the combination of a plasma vWf-Ag greater than 450 and nonpulmonary organ failure at the time of entry into the study had a positive predictive value of 80 % for acute lung injury . Also , a plasma vWf-Ag level greater than 450 had a positive predictive value of 80 % for identifying nonsurvivors . Thus , in patients with nonpulmonary sepsis , an elevated level of plasma vWf-Ag is a useful , early biochemical marker of endothelial injury and it has both predictive and prognostic value Introduction The endothelial specific angiopoietin (Ang)-Tie2 lig and -receptor system has been identified as a non-redundant mediator of endothelial activation in experimental sepsis . Binding of circulating Ang-1 to the Tie2 receptor protects the vasculature from inflammation and leakage , whereas binding of Ang-2 antagonises Tie2 signalling and disrupts endothelial barrier function . Here , we examine whether circulating Ang-1 and /or Ang-2 independently predict mortality in a cohort of critically ill medical patients . Methods Circulating vascular endothelial growth factor ( VEGF ) , Ang-1 and Ang-2 were prospect ively measured in sera from 29 healthy controls and 43 medical ICU patients by immunoradiometric assay ( IRMA ) and ELISA , respectively . Survival after 30 days was the primary outcome studied . Results Median serum Ang-2 concentrations were increasingly higher across the following groups : healthy controls , patients without sepsis , patients with sepsis and patients with septic shock . In contrast , Ang-1 and VEGF concentrations were significantly lower in all patient groups compared with healthy controls . Ang-2 correlated with partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen ( FiO2 ) , tissue hypoxia , Sequential Organ Failure Assessment ( SOFA ) and Physiology and Chronic Health Evaluation II ( APACHE II ) score . Multivariate Cox regression analyses confirmed a strong independent prognostic impact of high Ang-2 as a novel marker of 30-day survival . Conclusions A marked imbalance of the Ang-Tie system in favour of Ang-2 is present in critically ill medical patients . Our findings highlight the independent prognostic impact of circulating Ang-2 in critical illness . Ang-2 may be used as a readily available powerful predictor of outcome and may open new perspectives to individualise treatment in the ICU Abstract Angiogenesis is a key component of the repair mechanisms triggered by tissue injury . Vascular endothelial growth factor ( VEGF ) is an important mediator of angiogenesis , as it acts directly and specifically on endothelial cells . VEGF produced locally in regenerating tissue may spill over into the systemic circulation , and measuring levels of circulating VEGF may allow monitoring of angiogenesis . To determine whether circulating VEGF is increased after severe injury , we measured concentrations of VEGF in serial serum sample s of 23 mechanical burn patients , 55 patients with multiple trauma and 56 healthy normal controls , using a newly established ELISA assay . In burn patients , serum VEGF was increased on day 1 ( 369.4 ± 88.0 pg/ml ) and on day 3 ( 452.0 ± 65.3 pg/ml ) , reached highest levels on day 14 ( 1809.5 ± 239.7 pg/ml ) and was still elevated on day 21 post-burn ( 1339.8 ± 208.7 pg/ml ) ( mean ± SEM , p<0.01 ) , when compared with healthy controls ( 82.2 ± 10.8 pg/ml ( mean ± SEM ) ) . Likewise , in trauma patients , serum VEGF showed a trend towards elevated values on the day of admission ( 186.9 ± 43.9 pg/ml ) and on day 3 after injury ( 193.2 ± 62.1 pg/ml ) . Thereafter , serum VEGF increased further ( day 7 , 507.0 ± 114.7 pg/ml ) , peaked on day 14 ( 742.4 ± 151.8 pg/ml ) and was still elevated on day 21 after injury ( 693.1 ± 218.6 pg/ml ( mean ± SEM , p<0.01 ) ) . No significant correlation was observed between peak serum VEGF and initial severity of mechanical ( Injury Severity Score ) or burn injury ( percentage of body surface burned ) . However , in both burn and trauma patients , the subgroup of patients with uncomplicated healing showed significantly higher increases of serum VEGF than the subgroup who developed severe complications during the post-traumatic course , such as sepsis , adult respiratory distress syndrome or multiple organ failure ( p<0.05 ) . Thus , markedly enhanced levels of serum VEGF are present one to three weeks after trauma or burn injury . Further , occurrence of severe complications during the post-traumatic period is associated with lesser increases of serum VEGF Objective : To measure plasma levels of angiopoietin-1 ( Ang-1 ) , angiopoietin-2 ( Ang-2 ) , and vascular endothelial growth factor ( VEGF ) early after trauma and to determine their clinical significance . Background : Angiopoietins and VEGF play a central role in the physiology and pathophysiology of endothelial cells . Ang-2 has recently been shown to have pathogenetic significance in sepsis and acute lung injury . Little is known about the role of angiopoietins and VEGF early after trauma . Methods : Blood specimens from consecutive major trauma patients were obtained immediately upon arrival in the emergency department and plasma sample s assayed for Ang-1 , Ang-2 , VEGF , markers of endothelial activation , protein C pathway , fibrinolytic system , and complement . Base deficit was used as a measure of tissue hypoperfusion . Data were collected prospect ively . Results : Blood sample s were obtained from 208 adult trauma patients within 30 minutes after injury before any significant fluid resuscitation . Plasma levels of Ang-2 , but not Ang-1 and VEGF were increased and correlated independently with severity of injury and tissue hypoperfusion . Furthermore , plasma levels of Ang-2 correlated with markers of endothelial activation , coagulation abnormalities , and activation of the complement cascade and were associated with worse clinical outcome . Conclusions : Ang-2 is released early after trauma with the degree proportional to both injury severity and systemic hypoperfusion . High levels of Ang-2 were associated with an activated endothelium , coagulation abnormalities , complement activation , and worse clinical outcome . These data indicate that Ang-2 is a marker and possibly a direct mediator of endothelial activation and dysfunction after severe trauma Introduction Previous reports suggest that endothelial activation is an important process in sepsis pathogenesis . We investigated the association between biomarkers of endothelial cell activation and sepsis severity , organ dysfunction sequential organ failure assessment ( SOFA ) score , and death . Methods This is a prospect i ve , observational study including adult patients ( age 18 years or older ) presenting with clinical suspicion of infection to the emergency department ( ED ) of an urban , academic medical center between February 2005 and November 2008 . Blood was sample d during the ED visit and biomarkers of endothelial cell activation , namely soluble fms-like tyrosine kinase-1 ( sFlt-1 ) , plasminogen activator inhibitors -1 ( PAI-1 ) , sE-selectin , soluble intercellular adhesion molecule ( sICAM-1 ) , and soluble vascular cell adhesion molecule ( sVCAM-1 ) , were assayed . The association between biomarkers and the outcomes of sepsis severity , organ dysfunction , and in-hospital mortality were analyzed . Results A total of 221 patients were included : sepsis without organ dysfunction was present in 32 % , severe sepsis without shock in 30 % , septic shock in 32 % , and 6 % were non-infected control ED patients . There was a relationship between all target biomarkers ( sFlt-1 , PAI-1 , sE-selectin , sICAM-1 , and sVCAM-1 ) and sepsis severity , P < 0.05 . We found a significant inter-correlation between all biomarkers , including the strongest correlations between sFlt-1 and sE-selectin ( r = 0.55 , P < 0.001 ) , and between sFlt-1 and PAI-1 ( 0.56 , P < 0.001 ) . Among the endothelial cell activation biomarkers , sFlt-1 had the strongest association with SOFA score ( r = 0.66 , P < 0.001 ) , the highest area under the receiver operator characteristic curve for severe sepsis of 0.82 , and for mortality of 0.91 . Conclusions Markers of endothelial cell activation are associated with sepsis severity , organ dysfunction and mortality . An improved underst and ing of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis OBJECTIVE Soluble adhesion molecules are regarded to be markers of inflammation , endothelial activation , or damage . The influence of age on plasma concentrations of circulating adhesion molecules should be serially studied in critically ill intensive care patients . DESIGN Prospect i ve and descriptive study over 5 days . SETTING Clinical investigation in a surgical intensive care unit of a university hospital . PATIENTS Thirty critically ill patients ( Acute Physiology and Chronic Health Evaluation [ APACHE ] II score of > 15 points ) , with sepsis secondary to postoperative complications , were included in this study . Fifteen consecutive patients aged < 50 yrs and 15 consecutive patients aged > 70 yrs were prospect ively studied . INTERVENTIONS All patients were treated by the st and ard protocol s of our intensive care unit , which did not differ between the groups . The patients received continuous analgesia-sedation and mechanical ventilation . Intensivists caring for the patients were not involved in the study and were blinded to data analysis . MEASUREMENTS AND MAIN RESULTS Hemodynamic parameters were extensively monitored in all patients . From arterial blood sample s , plasma concentrations of soluble adhesion molecules ( endothelial leukocyte adhesion molecule-1 , intercellular adhesion molecule-1 , vascular cell adhesion molecule-1 , granule membrane protein-140 ) were measured on the day of admission ( i.e. , baseline values ) and during the following 5 days . Three of the younger patients and six of the elderly patients died during the study period ( p < .05 ) . Oxygen delivery and consumption , and the other hemodynamic data , were without group differences throughout the study . Plasma concentrations of all adhesion molecules were beyond normal at baseline in both groups . These concentrations increased further during the first 2 to 3 days in both groups , with a significantly higher increase in the elderly patients ( endothelial leukocyte adhesion molecule-1 to 179 + /- 32 ng/mL ; intercellular adhesion molecule-1 to 1695 + /- 158 ng/mL ; vascular cell adhesion molecule-1 to 1395 + /- 212 ng/mL ; and granule membrane protein-140 to 888 + /- 119 ng/mL ) . In the younger patients , concentrations of soluble adhesion molecules decreased later in the study and almost reached baseline values on day 5 . In the elderly patients , these concentrations remained significantly higher until the end of the study . CONCLUSIONS The higher plasma concentrations of the measured adhesion molecules in elderly critically ill patients indicate that elderly patients are more prone than younger patients to a more pronounced activation or even damage of the endothelium . Further work needs to be done to determine the prognostic importance and to define the role of soluble adhesion molecules , particularly in the elderly critically ill patient ObjectiveS epsis and systemic inflammatory response syndrome ( SIRS ) result in the release in plasma of inflammatory cytokines and soluble forms of adhesion molecules in relation to endothelial activation . This study was design ed to compare cerebrospinal fluid ( CSF ) concentrations of adhesion molecules in meningitis and SIRS without neurological infection and to evaluate in meningitis whether they originate from passive diffusion through damaged blood – CSF barrier or from local production . Design Prospect i ve observational study . Setting University hospital medical intensive Output:	Overall , published studies report positive correlations between multiple EC-derived molecules and the diagnosis of sepsis , supporting the critical role of EC activation in sepsis . Conclusions Multiple endothelial-derived molecules are positively correlated with the presence of sepsis in humans , and variably correlated to other clinical ly-important outcomes .
MS21621	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES : The lower esophageal sphincter ( LES ) , surrounded by diaphragmatic muscle , prevents gastroesophageal reflux . When these structures become incompetent , gastric contents may cause gastroesophageal reflux disease ( GERD ) . For treatment , lifestyle interventions are always recommended . We hypothesized that by actively training the crura of the diaphragm as part of the LES using breathing training exercises , GERD can be positively influenced . METHODS : A prospect i ve r and omized controlled study was performed . Patients with non-erosive GERD or healed esophagitis without large hernia and /or previous surgery were included . Patients were r and omized and allocated either to active breathing training program or to a control group . Quality of life ( QoL ) , pH-metry , and on-dem and proton pump inhibitor ( PPI ) usage were assessed at baseline and after 4 weeks of training . For long-term follow-up , all patients were invited to continue active breathing training and were further assessed regarding QoL and PPI usage after 9 months . Paired and unpaired t-test was used for statistical analysis . RESULTS : Nineteen patients with non-erosive GERD or healed esophagitis were r and omized into two groups ( 10 training group and 9 control group ) . There was no difference in baseline patient characteristics between the groups and all patients finished the study . There was a significant decrease in time with a pH<4.0 in the training group ( 9.1±1.3 vs. 4.7±0.9 % ; P<0.05 ) , but there was no change in the control group . QoL scores improved significantly in the training group ( 13.4±1.98 before and 10.8±1.86 after training ; P<0.01 ) , but no changes in QoL were seen in the control group . At long-term follow-up at 9 months , patients who continued breathing exercise ( 11/19 ) showed a significant decrease in QoL scores and PPI usage ( 15.1±2.2 vs. 9.7±1.6 ; 98±34 vs. 25±12 mg/week , respectively ; P<0.05 ) , whereas patients who did not train had no long-term effect . CONCLUSIONS : We show that actively training the diaphragm by breathing exercise can improve GERD as assessed by pH-metry , QoL scores and PPI usage . This non-pharmacological lifestyle intervention could help to reduce the disease burden of GERD Background The risk for acidic reflux is mainly determined by the position of the gastric acid pocket . It was hypothesised that compounds affecting proximal stomach tone might reduce gastro-oesophageal reflux by changing the acid pocket position . Objective To study the effect of azithromycin ( Azi ) on acid pocket position and acid exposure in patients with gastro-oesophageal reflux disease ( GORD ) . Methods Nineteen patients with GORD were included , of whom seven had a large hiatal hernia ( ≥3 cm ) ( L-HH ) and 12 had a small or no hiatal hernia ( S-HH ) . Patients were r and omised to Azi 250 mg/day or placebo during 3 days in a crossover manner . On each study day , reflux episodes were detected using concurrent high-resolution manometry and pH-impedance monitoring after a st and ardised meal . The acid pocket was visualised using scintigraphy , and its position was determined relative to the diaphragm . Results Azi reduced the number of acid reflux events ( placebo 8.0±2.2 vs Azi 5.6±1.8 , p<0.01 ) and postpr and ial acid exposure ( placebo 10.5±3.8 % vs Azi 5.9±2.5 % , p<0.05 ) in all patients without affecting the total number of reflux episodes . Acid reflux occurred mainly when the acid pocket was located above , or at the level of , the diaphragm , rather than below the diaphragm . Treatment with Azi reduced hiatal hernia size and result ed in a more distal position of the acid pocket compared with placebo ( below the diaphragm 39 % vs 29 % , p=0.03 ) . Azi reduced the rate of acid reflux episodes in patients with S-HH ( 38 % to 17 % ) to a greater extent than in patients with L-HH ( 69 % to 62 % , p=0.04 ) . Conclusion Azi reduces acid reflux episodes and oesophageal acid exposure . This effect was associated with a smaller hiatal hernia size and a more distal position of the acid pocket , further indicating the importance of the acid pocket in the pathogenesis of GORD . clinical trial registration http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=1970 NTR1970 The crural diaphragm ( CD ) is an essential component of the esophagogastric junction ( EGJ ) , and inspiratory exercises may modify its function . This study 's goal is to verify if inspiratory muscle training ( IMT ) improves EGJ motility and gastroesophageal reflux ( GER ) . Twelve GER disease [ GERD ; 7 males , 20 - 47 yr , 9 esophagitis , and 3 nonerosive reflex disease ( NERD ) ] and 7 healthy volunteers ( 3 males , 20 - 41 yr ) performed esophageal pH monitoring , manometry , and heart rate variability ( HRV ) studies . A 6-cm sleeve catheter measured average EGJ pressure during resting , peak inspiratory EGJ pressures during sinus arrhythmia maneuver ( SAM ) and inhalations under 17- , 35- , and 70-cmH2O loads ( TH maneuvers ) , and along 1 h after a meal . GERD patients entered a 5-days-a-week IMT program . One author scored heartburn and regurgitation before and after IMT . IMT increased average EGJ pressure ( 19.7 ± 2.4 vs. 29.5 ± 2.1 mmHg ; P < 0.001 ) and inspiratory EGJ pressure during SAM ( 89.6 ± 7.6 vs. 125.6 ± 13.3 mmHg ; P = 0.001 ) and during TH maneuvers . The EGJ-pressure gain across 35- and 70-cmH2O loads was lower for GERD volunteers . The number and cumulative duration of the transient lower esophageal sphincter relaxations decreased after IMT . Proximal progression of GER decreased after IMT but not the distal acid exposure . Low-frequency power increased after IMT and the higher its increment the lower the increment of supine acid exposure . IMT decreased heartburn and regurgitation scores . In conclusion , IMT improved EGJ pressure , reduced GER proximal progression , and reduced GERD symptoms . Some GERD patients have a CD failure , and IMT may prove beneficial as a GERD add-on treatment OBJECTIVES The prevalence of gastroesophageal reflux disease ( GERD ) in patients with laryngopharyngeal disorders is probably greater than realized . STUDY DESIGN Prospect i ve study . METHODS To investigate the incidence of gastroenterological diseases including GERD in patients complaining of nonspecific laryngopharyngeal symptoms , laryngological examinations and gastroenterological evaluation with esophagogastroduodenoscopy were performed in 30 patients who refused to undergo 24-hour pH monitoring . Therapeutic intervention by behavioural and dietary modifications , antireflux medication , and eradication of Helicobacter pylori were assessed for changes in laryngeal findings and relief of symptoms . RESULTS Posterior laryngitis was present in 26 patients and in 19 of them was accompanied by erythema and edema of the interarytenoid region . Gastroenterological diseases such as GERD ( 43 % ) , hiatal hernia ( 43 % ) , and Helicobacter pylori-positive antrum gastritis ( 23 % ) were confirmed in 22 ( 73 % ) cases by esophagogastroduodenoscopy and histological examination of biopsy specimens . Medical antireflux treatment and eradication of Helicobacter pylori result ed in a remarkably therapeutic success rate of 90 % because there was resolution of laryngopharyngeal symptoms and laryngeal findings in 20 of 22 patients with gastroenterological diseases for the mean follow-up period of 8 months . CONCLUSIONS Laryngopharyngeal symptoms can be predictors of gastroesophageal diseases and GERD because the most frequent underlying cause is supposed to be associated with posterior laryngitis . Medical antireflux treatment is effective for relief of symptoms and mucosal healing of posterior laryngitis The treatment of gastroesophageal reflux disease may be clinical or surgical . The clinical consists basically of the use of drugs ; however , there are new techniques to complement this treatment , osteopathic intervention in the diaphragmatic muscle is one these . The objective of the study is to compare pressure values in the examination of esophageal manometry of the lower esophageal sphincter ( LES ) before and immediately after osteopathic intervention in the diaphragm muscle . Thirty-eight patients with gastroesophageal reflux disease - 16 su bmi tted to sham technique and 22 su bmi tted osteopathic technique - were r and omly selected . The average respiratory pressure ( ARP ) and the maximum expiratory pressure ( MEP ) of the LES were measured by manometry before and after osteopathic technique at the point of highest pressure . Statistical analysis was performed using the Student 's t-test and Mann-Whitney , and magnitude of the technique proposed was measured using the Cohen 's index . Statistically significant difference in the osteopathic technique was found in three out of four in relation to the group of patients who performed the sham technique for the following measures of LES pressure : ARP with P= 0.027 . The MEP had no statistical difference ( P= 0.146 ) . The values of Cohen d for the same measures were : ARP with d= 0.80 and MEP d= 0.52 . Osteopathic manipulative technique produces a positive increment in the LES region soon after its performance BACKGROUND Proton pump inhibitors ( PPIs ) are a major breakthrough in the medical management of gastroesophageal reflux disease ( GERD ) . In several patients with non erosive reflux disease symptoms ( NERD ) the response to PPIs is partial or limited and symptoms relief needs the administration of additional medications . AIM The aim of this study was to evaluate the effect of a new medical device , based on an oral fixed combination of hyaluronic acid and chondroitin-sulphate ( HA+CS ) , in a bioadhesive carrier , in adults with symptoms of non erosive gastroesophageal reflux and with a low response to PPIs . PATIENTS AND METHODS Twenty patients who had experienced heartburn and /or acid regurgitation for at least 3 days during a 7 day run-in period , without endoscopic mucosal breaks , were r and omized in a double blind crossover study to receive four daily doses of a fixed oral combination of HA+CS and placebo for 14 days . Relief of cardinal symptoms of GERD was evaluated at the end of each period . RESULTS A significant greater Sum of Symptoms Intensity Difference , compared to placebo , was observed after HA+CS treatment ( -2.7 vs 0.5 - p < 0.01 ) , being both heartburn ( -1.6 vs 0.5 - p < 0.03 ) and acid regurgitation ( -1.1 vs 0.1 - p < 0.03 ) significantly improved by the medical device . A speed of action ≤ 30 min was significantly more frequently reported by patients during HA+CS administration than with placebo ( 60 % vs 30 % - p = 0.05 ) . Total disappearance of symptoms was observed in 50 % of the patients compared to 10 % during placebo administration ( p = 0.01 between group comparison ) . CONCLUSIONS A fixed combination of HA+CS has demonstrated to be effective in gastroesophageal reflux control , with a rapid onset of action Output:	Among the non-surgical , non-pharmacological treatment modalities , the breathing training on diaphragm could play an important role in selected patients to manage the symptoms of GERD
MS21622	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In a prospect i ve , r and omized study , 58 patients with primary cemented hip arthroplasty and 39 patients with primary cemented knee arthroplasty were divided into groups with postoperative closed-suction drainage and without drainage . There was no difference in healing of the wounds , postoperative blood transfusions , complications , or range of motion . Although there was more soaked dressing requiring reinforcements in the groups without drainage , as a result of this study , we no longer use drains in uncomplicated cemented primary hip and knee arthroplasties for osteoarthritis Abstract A prospect i ve evaluation of 98 patients who had undergone a total hip or knee arthroplasty was conducted to assess the effect of postoperative suction drainage . Sixty-six patients undergoing elective total hip arthroplasty and 32 patients undergoing total knee replacement were r and omly allocated to undergo either suction drainage or no drainage of the wound . Statistical analysis of the results showed no difference in wound healing , severity of wound haematoma , postoperative blood transfusion requirement , range of motion and duration of the hospitalization between the two groups . We conclude that the use of closed suction drainage provides no apparent advantage after uncomplicated total hip or knee arthroplasty Purpose of the study Suction drainage in bipolar arthroplasty for hip fracture is st and ard procedure despite the lack of a solid scienfific basis . No study is reported in the literature demonstrating an advantage of systematic drainage . The aim of this work was to search for reasons why this conventional practice should be continued , Material and method es A prospect i ve r and omized stydt in a homogeneous consecutive group of patients hospitalized in our unit for hip fracture were included in the study from January 1995 through January 1999 . Among the 183 patients , 97 were excluded ( hemostasis disorders or anticoagulant treatment , multiple fractures , preoperative anemia with Hg < 9.5 g/dl , postponed operation ) . For the 86 included patients , the posterolateral Moore access was used to implant a sealed intermediary prosthesis . According to r and om selection , drainage was then installed or not . Outcome criteria were number of reoperations , hemoglobin level on DO , D1 , D2 , D5 , and D10 , number of patients requiring transfusion and number of packed red cell units in each group , and finally , temperature as reflecting presence of possible hematome ( DO , D2 , D5 , D10 ) . Results The two groups were similar for age and sex . There were no reoperations for hematoma or superficial infection and only one patient was reoperated for early dislocation in the group without drainage . Twenty-seven patients had transfusions , 14 in the drainage group and 13 in the no drainage group ; mean number of packed red cell units was 2 . Hemoglobin level fell similarly in the two groups in DO ( 2.1 versus 1.9 ) , D2 ( 2.5 versus 2.4 ) , D ( 2.7 versus 2.7 ) , D10 ( 2.4 versus 2.6 ) as did mean temperatures . Discussion We were thus unable to demonstrate any advantage of using suction drainage in bipolar arthroplasty for hip fracture when using more access . This is in agreement with reports in the literature . Exception the simplification of nursing care by not using drains , the cost savings can be considerable in light of the number of patients treated . We recommend that systematic use of suction drainage be discontinued in bipolar arhtroplasty for hip fracture The routine use of surgical drains in total hip arthroplasty remains controversial . They have not been shown to decrease the rate of wound infection significantly and can provide a retro grade route for it . Their use does not reduce the size or incidence of post-operative wound haematomas . This prospect i ve , r and omised study was design ed to evaluate the role of drains in routine total hip arthroplasty . We investigated 552 patients ( 577 hips ) undergoing unilateral or bilateral total hip arthroplasty who had been r and omised to either having a drain for 24 hours or not having a drain . All patients followed st and ardised pre- , intra- , and post-operative regimes and were independently assessed using the Harris hip score before operation and at six , 18 and 36 months follow-up . The rate of superficial and deep infection was 2.9 % and 0.4 % , respectively , in the drained group and 4.8 % and 0.7 % , respectively in the undrained group . One patient in the undrained group had a haematoma which did not require drainage or transfusion . The rate of transfusion after operation in the drained group was significantly higher than for undrained procedures ( p < 0.042 ) . The use of a drain did not influence the post-operative levels of haemoglobin , the revision rates , Harris hip scores , the length of hospital stay or the incidence of thromboembolism . We conclude that drains provide no clear advantage at total hip arthroplasty , represent an additional cost , and expose patients to a higher risk of transfusion We report on a prospect i ve r and omized trial on the effect of wound drains on wound healing following surgery for proximal femoral fractures . One hundred and seventy-seven consecutive patients admitted to Queen 's Medical Centre Nottingham , undergoing AO dynamic hip screw ( DHS ) or hemiarthroplasty were r and omized whether or not to receive wound drainage . Wound healing was assessed in terms of ultrasound examination , the ASEPSIS wound score system and overt infection rates . All patients were followed up at 6 weeks and 6 months . Ultrasound examinations showed that drains were indeed ineffective in preventing haematoma formation , the first time this has been demonstrated objective ly . However , using drains failed to prevent late seroma formation . Patients who received wound drainage showed statistically better wound healing on the ASEPSIS wound scoring system and a reduced infection rate . The ASEPSIS scores on day 2 and 5 postoperatively proved an accurate predictor of poor wound healing . This study conflicts with previous smaller studies which failed to show an effect of wound drainage upon wound healing , and strongly supports the use of wound drains In a r and omized clinical study on 40 intraarticular knee joint drainages the effect of a high vacuum , middle vacuum , low vacuum and suction free drainages were examined . The maximum of the volume that was drained had been in the group of the suction free drainages . Drains with a long period of suction had a minimum of evaluated ultrasonographic effusion in the knee joint . The group with high vacuum was obviously not as long as open as in the other groups . Thrombi in the drainages could be found in every group . This refers to the observation that the finding of adherent thrombi is related to the material the drain is made of . Adherent thrombi decrease the possibility of secretion , not adherent thrombi do not decrease suction volume . Referring to these results it is obvious that not the high-vacuum drainage is the matter of choice for intraarticular drains . The suction-free drainages or drains with reduced vacuum have more advantages in respect to simple , secure and fast implantation and h and ling A prospect i ve study of thirty-eight patients ( seventy-six knees ) who had had a primary bilateral total knee replacement and twelve patients ( twenty-four hips ) who had had a primary bilateral total hip replacement was conducted to assess the effect of postoperative suction drainage on wound-healing . A suction drain was placed on each patient 's right operative wound , while no drains were used on the left . Otherwise , the same operative technique and method of closure were used in all wounds . Statistical analysis of the results showed no difference between the two sides with regard to the incidences of swelling or persistent drainage . Return of active function of the quadriceps and of range of motion of the knee in patients who had had a total knee replacement was also unaffected by the use of suction drains . We concluded that the routine use of suction drains for wounds is unnecessary after uncomplicated total joint arthroplasty One hundred fifteen consecutive patients undergoing TKR were divided into two groups to determine whether blood loss and transfusion in total knee replacement ( TKR ) using adrenaline with saline infiltration would be less than TKR with tourniquet and drain . Group 1 , composed of 60 patients , received 2.5 mg of 1:1000 adrenaline diluted in 500 mL of normal saline , which was infiltrated into the skin , subcutaneous tissues , and capsule before surgical incision . No tourniquets or postoperative drains were used . Group 2 , composed of 55 patients , had a tourniquet and postoperative drain . Thromboprophylaxis with low molecular weight heparin also was used . Pre- and postoperative hemoglobin , blood loss , hematocrit , and transfusion requirements were studied in both groups ; in group 2 , blood loss in the drains also was noted . Average preoperative hemoglobin and hematocrit in the two groups were 13.7 g/dL and 39.3 g/dL , respectively , and 13.5 % and 39 % , respectively . Average intraoperative blood loss was 290 mL in group 1 and 377.7 mL in group 2 ( P<.005 ) . Postoperative blood loss in group 1 was < 50 mL based on dressing soakage and 297.7 mL in group 2 ( P<.005 ) . Average postoperative hemoglobin and hematocrit in the two groups were 10.6 g/dL and 8.4 g/dL , respectively , and 35.4 % and 31.1 % , respectively . Transfusion rates were 3.3 % and 23.6 % , respectively ( P<.005 ) . The average volume transfused was 1.2 U. Adrenaline and saline infiltration is safe and helps reduce intraoperative blood loss . Suction drain use for surgical wounds after primary , uncomplicated TKR is question able The goal of this study is to report our experience with the use of suction drainage for various arthroscopic knee procedures . One hundred and ninety patients who underwent arthroscopic knee procedures participated in the study , and were divided into two groups ( Group 1 : Suction drainage , Group 2 : No suction drainage ) . For every patient , the following parameters were recorded : age , gender , operative time , tourniquet or pump use , the amount of fluid collected in the hemovac drain , presence of meniscal tear , type of the operative procedure , date of the operation , and presence of effusion at the follow-up . Statistical analysis was performed to detect any significant statistical difference between the amount of fluid collected in the hemovac drain and the other mentioned parameters in Group 1 ; and these patients were divided into four subgroups to facilitate the statistical evaluation between the procedures and the amount of fluid collected in the hemovac drain . The partial meniscectomy subgroup had significantly lower amounts of collected fluid when compared to the subtotal meniscectomy subgroup . Drilling of the osteochondral faces led to significantly higher amounts of fluid when compared to non-drilling cases . Use of an infusion pump during surgery and shorter operation time led to lower amounts of fluid to be collected . No case in either main group suffered from effusion at the follow-up . Our investigation demonstrated that in different arthroscopic interventions , variable amounts of fluid can be collected in the hemovac drains . Subtotal meniscal resection , drilling of the osteochondral faces and longer duration of the operation increase the amount of fluid . In cases of partial meniscal resection and /or chondral debridement , limited synovial and plica resection , suction drainage is unnecessary A r and omized , controlled study compared the effects of wound compression with drainage after primary total hip arthroplasty . In 51 patients , an inflatable cuff was placed over the wound underneath a girdle ( System Calmed , Calmed AB , Askim , Sweden ) . Control patients had wound drainage ( n = 54 ) . Preoperative and intraoperative variables did not differ between groups . Total blood loss was calculated using hemoglobin balance ; with compression it was 1510 + /- 656 mL ( mean + /- SD ) and in controls 1695 + /- 712 mL ( P = .13 ) . However , less blood was transfused in the compression group ( P = .05 ) . Wound infection was seen in 2 patients with compression and in 3 controls . Deep venous thrombosis occurred in 3 controls . Wound discharge was more frequent in controls ( 19/54 vs 8/51 ; P = .04 ) . Thus , wound compression had no obvious negative effects and reduced wound discharge and need for transfusion . It may replace drainage after total hip arthroplasty A prospect i ve , r and omized study was performed to assess the effectiveness of postoperative closed suction drainage . One hundred and twelve consecutive procedures involving autologous iliac-crest bone graft were performed , from December 29 , 1992 , to July 1 , 1993 , following a traumatic injury of the spine in 108 patients . Sixty of the sites from which the bone graft had been obtained were drained with a single large Hemovac device . The drains were maintained for two to five days postoperatively . The remaining fifty-two incisions were closed without a drainage device . All patients were evaluated clinical ly for problems with wound-healing . The incisions were considered to be healed when they had been asymptomatic for one year . Of eleven patients who had problems with wound-healing , six had been managed with a drain and five had not . The findings of this study do not support Output:	Pooling of results indicated no statistically significant difference in the incidence of wound infection , haematoma , dehiscence or re-operations between those allocated to drains and the un-drained wounds . Blood transfusion was required more frequently in those who received drains . The need for reinforcement of wound dressings and the occurrence of bruising were more common in the group without drains . There is insufficient evidence from r and omised trials to support the routine use of closed suction drainage in orthopaedic surgery .
MS21623	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background and Purpose — Transcranial color-coded duplex sonography ( TCCS ) allows bedside imaging of intracranial hemodynamics and parenchymal structures . It provides reliable information regarding midline shift ( MLS ) in space-occupying hemispheric stroke . We studied the value of MLS measurement to predict fatal outcome at different time points after stroke onset . Methods — Forty-two patients with acute , severe hemispheric stroke were enrolled . Cranial computed tomography ( CCT ) and extracranial duplex sonography were performed on admission . TCCS was carried out 8±3 , 16±3 , 24±3 , 32±3 , and 40±3 hours after stroke onset . Lesion size was determined from follow-up CCT . Results — Twelve patients died as the result of cerebral herniation ( group 1 ) ; 28 survived ( group 2 ) . Two patients received decompressive hemicraniectomy and were therefore excluded from further evaluation . MLS was significantly higher in group 1 as early as 16 hours after onset of stroke . Specificity and positive predictive values for death caused by cerebral herniation of MLS ≥2.5 , 3.5 , 4.0 , and 5.0 mm after 16 , 24 , 32 , and 40 hours were 1.0 . Conclusions — TCCS helps to estimate outcome as early as 16 hours after stroke onset and thus facilitates identification of patients who are unlikely to survive without decompressive craniectomy . Because of its noninvasive character and bedside suitability , sonographic monitoring of MLS might be a useful tool in management of critically ill patients who can not undergo repeated CCT scans BACKGROUND AND PURPOSE Malignant , space-occupying supratentorial ischemic stroke is characterized by a mortality rate of up to 80 % . Several reports indicate a beneficial effect of hemicraniectomy in this situation . However , whether and when decompressive surgery is indicated in these patients is still a matter of debate . METHODS In an open , prospect i ve trial we performed hemicraniectomy in 63 patients with acute complete middle cerebral artery infa rct ion . Initial clinical presentation was assessed by the Sc and inavian Stroke Scale ( SSS ) and the Glasgow Coma Scale ( GCS ) . All survivors were reexamined 3 months after surgical decompression , with the clinical evaluation grade d according to the Rankin Scale ( RS ) and Barthel Index ( BI ) . We analyzed the influence of early decompressive surgery ( < 24 hours after symptom onset , based on clinical status at admission and initial CT findings ) versus late surgery ( > 24 hours after first reversible signs of herniation ) on mortality , functional outcome , and the length of time of critical care therapy was needed . RESULTS In total , 46 patients ( 73 % ) survived . Despite complete hemispheric infa rct ion , no survivor suffered from complete hemiplegia or was permanently wheelchair bound . In patients with speech-dominant hemispheric infa rct ion ( n=11 ) , only mild to moderate aphasia was present . The mean BI score was 65 , and RS score revealed severe h and icap in 13 % of the patients . In 31 patients with early decompressive surgery , mortality was 16 % and BI score 68.8 . Early hemicraniectomy led to a significant reduction in the length of time critical care therapy was needed ( 7.4 versus 13.3 days , P<0.05 ) . CONCLUSIONS In general , the outcome of patients treated with craniectomy in severe ischemic hemispheric infa rct ion was surprisingly good . In addition , early decompressive surgery may further improve outcome in these patients BACKGROUND AND PURPOSE Early identification of acute stroke patients at risk of fatal brain swelling is necessary to facilitate implementation of aggressive therapies . Initial clinical , laboratory , and CT characteristics that may be used as selection criteria were analyzed to determine predictors of herniation and neurological death . METHODS Data from the placebo arm of the Lubeluzole-International-9 trial were review ed to identify patients with fatal brain edema . Early clinical , laboratory , and radiographic parameters were evaluated in a case-control design . Initial CT scans were analyzed for early ischemic abnormalities by 2 blinded investigators . RESULTS Twenty-three patients died from brain swelling , with minimum baseline National Institutes of Health Stroke Scale ( NIHSS ) scores of 20 ( n=12 ; mean , 23.2+/-1.8 ) with left and 15 ( n=11 ; mean , 17.6+/-2.2 ) with right hemispheric infa rct ions ( P=0 . 0001 ) . A sample of 112 subjects with comparably severe strokes , but who did not die from brain swelling , was selected from the remaining population according to the same NIHSS scores . Among clinical and laboratory characteristics , nausea/vomiting within 24 hours after onset ( odds ratio [ OR ] , 5.1 ; 95 % CI , 1.7 to 15.3 ; P=0.003 ) and 12-hour systolic blood pressure > /=180 mm Hg ( OR , 4.2 ; 95 % CI , 1.4 to 12.9 ; P=0.01 ) were independently associated with fatal brain swelling . Among radiographic factors , only hypodensity of > 50 % of the middle cerebral artery territory on initial CT scan was an independent predictor ( OR , 6.1 ; 95 % CI , 2.3 to 16.6 ; P=0.0004 ) . CONCLUSIONS Patients with baseline NIHSS score > /=20 with left or > /=15 with right hemispheric infa rct ions within 6 hours of symptom onset who also have nausea/vomiting or > 50 % middle cerebral artery territory hypodensity are at high risk for developing fatal brain swelling BACKGROUND AND PURPOSE To predict malignant course in patients with large middle cerebral artery ( MCA ) infa rct ion , we combined PET imaging and neuromonitoring , including microdialysis . METHODS Thirty-four patients with stroke of > 50 % of the MCA territory in early cerebral CT scan were included . Probes for microdialysis and measurement of intracranial pressure and tissue oxygen pressure ( Pto2 ) were placed into the ipsilateral frontal lobe . PET was performed with 11C-flumazenil to assess CBF and irreversible neuronal damage . RESULTS PET measurements within 24 hours after stroke showed larger volumes of ischemic core ( mean , 144.5 versus 62.2 cm3 ) and larger volumes of irreversible neuronal damage ( 157.9 versus 47.0 cm3 ) in patients with malignant course ( ie , edema formation with midline shift ) than in patients with benign course . Mean cerebral blood flow values within the ischemic core were significantly lower and the volume of the ischemic penumbra was smaller in the malignant than in the benign group . In patients with malignant course , cerebral perfusion pressure dropped to < 50 to 60 mm Hg 22 to 72 hours ( mean , 52.0 hours ) after onset of symptoms ; subsequently , Pto2 dropped and glutamate increased , indicating secondary ischemia . Maximal changes in the monitored variables reached significant levels for glutamate , aspartate , GABA , glycerol , lactate-to-pyruvate ratio , hypoxanthine , intracranial pressure , cerebral perfusion pressure , and Pto2 . CONCLUSIONS PET allowed prediction of malignant MCA infa rct ion within the time window suggested for hemicraniectomy . Neuromonitoring helped to classify the clinical courses by characterizing pathophysiological sequelae of malignant edema formation . In contrast to PET , however , it did not predict fatal outcome early enough for successful implementation of invasive therapies BACKGROUND In laboratory animals , cerebral ischaemia is worsened by hyperthermia and improved by hypothermia . Whether these observations apply to human beings with stroke is unknown . We therefore examined the relation between body temperature on admission with acute stroke and various indices of stroke severity and outcome . METHODS In a prospect i ve and consecutive study 390 stroke patients were admitted to hospital within 6 h after stroke ( median 2.4 h ) . We determined body temperature on admission , initial stroke severity , infa rct size , mortality , and outcome in survivors . Stroke severity was measured on admission , weekly , and at discharge on the Sc and inavian Stroke Scale ( SSS ) . Infa rct size was determined by computed tomography . Multiple logistic and linear regression outcome analyses included relevant confounders and potential predictors such as age , gender , stroke severity on admission , body temperature , infections , leucocytosis , diabetes , hypertension , atrial fibrillation , ischaemic heart disease , smoking previous stroke , and comorbidity . FINDINGS Mortality was lower and outcome better in patients with mild hypothermia on admission ; both were worse in patients with hyperthermia . Body temperature was independently related to initial stroke severity ( p < 0.009 ) , infa rct size ( p < 0.0001 ) , mortality ( p < 0.02 ) , and outcome in survivors ( SSS at discharge ) ( p < 0.003 ) . For each 1 degrees C increase in body temperature the relative risk of poor outcome ( death or SSS score on discharge < 30 points ) rose by 2.2 ( 95 % CI 1.4 - 3.5 ) ( p < 0.002 ) . INTERPRETATION We have shown that , in acute human stroke , an association exists between body temperature and initial stroke severity , infa rct size , mortality , and outcome . Only intervention trials of hypothermic treatment can prove whether this relation is causal Analysis of early deaths after stroke is important , since some deaths may be preventable . Previous studies have relied on retrospective and often incomplete clinical data , for comparison with pathological findings . The present study is based on 1073 consecutive stroke patients admitted to an intensive care stroke unit from a well-defined population . There were 212 deaths within the first 30 days , yielding a mortality rate of 20 % . Clinical , radiological , and laboratory data were collected prospect ively according to a st and ardized protocol . Autopsies were performed on 90 of the 212 patients , and CT scanning on a further 27 . Early mortality after stroke exhibits a bimodal distribution . One peak occurs during the first week , and a second during the second and third weeks . The majority of deaths in the first week are due to transtentorial herniation . Of these , deaths due to hemorrhage usually occur within the first three days , whilst deaths due to infa rct ion peak between the third and sixth day post ictus . After the first week , deaths due to relative immobility ( pneumonia , pulmonary embolism and sepsis ) predominate , peaking towards the end of the second week . Cardiac deaths occur throughout the first month , and unfortunately account for many deaths in patients with small functional deficits . Stroke VOL 15 , No 3 , BACKGROUND AND PURPOSE No neuroradiological markers have been characterized that support a timely decision for decompressive surgery in malignant middle cerebral artery ( MCA ) infa rct ion ( mMCAI ) . This case-control study was design ed to analyze whether early cerebral CT ( CCT ) scanning provides reliable information for the prospect i ve selection of stroke patients at risk of developing mMCAI . METHODS Thirty-one pairs ( n=62 ) were formed with cases ( mMCAI ) and controls ( acute but not malignant MCA infa rct ion ) closely matched in terms of age , sex , and stroke etiology . CCT was performed within 18 hours of stroke onset and analyzed by a blinded neuroradiologist according to a defined panel of 12 CCT criteria . RESULTS In terms of predicting mMCAI , the criteria of extended MCA territory hypodensities > 67 % and > 50 % , hemispheric brain swelling , midline shift , and hyperdense MCA sign exhibited high specificity ( 100 % , 93 . 5 % , 100 % , 96.7 % , and 83.9 % , respectively ) but low sensitivity ( 45.2 % , 58.1 % , 12.9 % , 19.4 % , and 70.9 % , respectively ) . Two criteria yielded high sensitivity ( subarachnoid space compressed , 100 % ; cella media compressed , 80.6 % ) but low specificity ( 29 % and 74.2 % , respectively ) . The criterion of attenuated corticomedullary contrast yielded both high specificity ( 96.8 % ) and sensitivity ( 87.1 % ) . The latter remained as the crucial criterion [ Exp(B)=90.8 ; 95 % CI , 5.8 to 1427 . 5 ] in a 2-tailed logistic regression analysis with the strongest correlating parameters ( Spearman correlation factor > /=0.6 or < /=-0.6 ) . CONCLUSIONS The analysis of CCT scans within 18 hours of stroke onset revealed an attenuated corticomedullary contrast as the crucial CCT criterion , which , with both sufficient sensitivity and specificity , predicted mMCAI with 95 % certainty Background and Purpose — Cerebral venous pressure is governed by intracranial pressure , cerebral perfusion pressure , and venous outflow resistance . Therefore , changes in venous flow velocities are to be expected because of changes Output:	Results : Infa rct size was the major determinant of the development of life-threatening edema . Other associated determinants were early mass effect , involvement of other vascular territories , higher body temperature , internal carotid artery occlusion , and need for mechanical ventilation . However , predictive values were only moderate . Conclusions : The size of the ischemic area is the major determinant . Single predictors lack sufficient predictive value to select c and i date s for surgical decompression before the onset of clinical signs of herniation
MS21624	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Study Design . Prospect i ve cohort study . Objective . To evaluate whether the DASH is not only a valid and responsive instrument to measure patients with shoulder , arm , and h and complaints , but also to evaluate patients with neck complaints . Summary of Background Data . The DASH has shown to be a valid and responsive question naire to evaluate disability in patients with shoulder , arm , and h and complaints . However , patients with shoulder , arm , or h and complaints frequently report neck complaints as well . Therefore , a valid and responsive question naire design ed for the whole upper extremity , including the neck , would be very useful and practical in upper-extremity research . Methods . Six hundred seventy-nine patients visiting their general practitioner with a new episode of nontraumatic complaints of the neck and upper extremity were evaluated by use of question naires at baseline and at 6-months follow-up . Six (sub)groups were formulated according to the location of complaints , including a subgroup with complaints in the shoulder-arm-h and region only and a group with complaints of the neck only . Disability ( DASH ) , general health [ SF-12 ( physical and mental component ) ] , severity , and persistence of complaints were assessed . Construct validity , floor and ceiling effects , and responsiveness were studied . Results . Correlations between the DASH and the other measures within the 6 (sub)groups at baseline ( construct validity ) , for the change scores at 6-months follow-up ( responsiveness ) , and the responsiveness ratios were classified as acceptable . No floor and ceiling effects were found . Conclusion . The DASH performed well with regard to the a priori hypotheses . This study has shown acceptable validity and responsiveness of the DASH for use in patients with nontraumatic neck complaints in addition to shoulder , arm , and h and complaints . We would caution against using the DASH in patients with neck complaints only , since fewer of the hypotheses could be confirmed in this subgroup Study Design . An observational prospect i ve cohort study in general practice . Objectives . To describe the clinical course and to identify predictors of recovery , changes in pain intensity , and changes in functional disability in patients with neck or shoulder symptoms at 3- and 12-month follow-up . Summary of Background Data . Knowledge on the clinical course and predictors of outcome in neck and shoulder symptoms is limited . Such knowledge would facilitate treatment decisions and may help to inform patients about their prognosis . Methods . Four hundred and forty-three patients who consulted their general practitioner with neck or shoulder symptoms participated in the study . Baseline scores of pain and disability , symptom characteristics , sociodemographic and psychological factors , social support , physical activity , general health , and comorbidity were investigated as possible predictors of recovery , changes in pain intensity , and changes in functional disability using multiple regression analyses . Results . The recovery rate was low ; 24 % of the patients reported recovery at 3 months and 32 % reported recovery at 12-month follow-up . Duration of the symptoms before consulting the GP and a history of neck or shoulder symptoms increased the probability of an unfavorable outcome . Furthermore , less vitality and more worrying were consistently associated with poorer outcome after 3 and 12 months . The area under the receiver-operator characteristic curve for the model predicting recovery was 0.8 at 3 months and 0.75 at 12 months . The explained variance of the models on pain and functional disability ranged from 43 to 54 % . Conclusions . The results found in this study indicate that besides clinical characteristics , psychological factors also predict the outcome of neck and shoulder symptoms Objectives For the measurement of patient-reported outcomes , such as ( health-related ) quality of life , often many measurement instruments exist that intend to measure the same construct . To facilitate instrument selection , our aim was to develop a highly sensitive search filter for finding studies on measurement properties of measurement instruments in PubMed and a more precise search filter that needs less abstract s to be screened , but at a higher risk of missing relevant studies . Methods A r and om sample of 10,000 PubMed records ( 01 - 01 - 1990 to 31 - 12 - 2006 ) was used as a gold st and ard . Studies on measurement properties were identified using an exclusion filter and h and search ing . Search terms were selected from the relevant records in the gold st and ard as well as from 100 systematic review s of measurement properties and combined based on sensitivity and precision . The performance of the filters was tested in the gold st and ard as well as in two validation sets , by calculating sensitivity , precision , specificity , and number needed to read . Results We identified 116 studies on measurement properties in the gold st and ard . The sensitive search filter was able to retrieve 113 of these 116 studies ( sensitivity 97.4 % , precision 4.4 % ) . The precise search filter had a sensitivity of 93.1 % and a precision of 9.4 % . Both filters performed very well in the validation sets . Conclusion The use of these search filters will contribute to evidence -based selection of measurement instruments in all medical fields OBJECTIVE To determine the prevalence , interrelation , and impact of musculoskeletal disorders of the upper limb in the general population . METHODS A total of 9,696 r and omly selected adults of working age were surveyed in a 2-stage cross-sectional study involving a screening question naire and a st and ardized physical examination in symptomatic subjects . Age- and sex-specific prevalence rates were estimated for several musculoskeletal disorders and for nonspecific pain in the upper limbs . The overlap and impact on daily activities and healthcare utilization were explored . RESULTS Among 6,038 first-stage responders , 3,152 reported upper limb symptoms and 1,960 were subsequently examined . Of subjects with pain , 44.8 % had 1 or more specific soft-tissue disorders . Site-specific prevalence rates were as follows : shoulder tendinitis 4.5 % among men and 6.1 % among women ; adhesive capsulitis 8.2 % among men and 10.1 % among women ; lateral epicondylitis 1.3 % among men and 1.1 % among women ; de Quervain 's disease 0.5 % among men and 1.3 % among women ; other tenosynovitis of the h and or wrist , 1.1 % among men and 2.2 % among women . Specific disorders tended to cluster ( P < 0.001 ) in individuals , with particular overlap at the shoulder . Compared with subjects with nonspecific pain , those with specific disorders more often reported inability to perform everyday tasks ( P < 0.05 ) , consultation with a doctor ( P < 0.05 ) , and use of prescribed medication ( P < 0.05 ) . CONCLUSION Upper limb pain is common in the general population and is often associated with physical signs suggestive of specific upper-limb disorders . These disorders have a substantial impact on physical function and use of health care Background : Epidemiological research in the field of soft tissue neck and upper limb disorders has been hampered by the lack of an agreed system of diagnostic classification . In 1997 , a United Kingdom workshop agreed consensus definitions for nine of these conditions . From these criteria , an examination schedule was developed and vali date d in a hospital setting . Objective : To investigate the reliability of this schedule in the general population . Methods : Ninety seven adults of working age reporting recent neck or upper limb symptoms were invited to attend for clinical examination consisting of inspection and palpation of the upper limbs , measurement of active and passive ranges of motion , and clinical provocation tests . A doctor and a trained research nurse examined each patient separately , in r and om order and blinded to each other 's findings . Results : Between observer repeatability of the schedule was generally good , with a median κ coefficient of 0.66 ( range 0.21 to 0.93 ) for each of the specific diagnoses considered . Conclusion : As expected , the repeatability of tests is poorer in the general population than in the hospital clinic , but the Southampton examination schedule is sufficiently reproducible for epidemiological research in the general population Study Design . A prospect i ve , multicenter , cross-sectional analysis of data from the National Spine Network data base . Objectives . To compare the relative impact of radicular and axial symptoms associated with disease of the cervical spine on general health as measured by the SF-36 Health Survey , and to compare the impact of these symptoms among patients of varying age and symptom duration . Background . Degenerative disorders of the cervical spine can cause debilitating symptoms of neck and arm pain . Physicians generally treat radiculopathy more aggressively than axial neck pain alone , although it has never been shown that the presence of radiculopathy leads to a greater impairment of physical and mental function . Material s and Methods . SF-36 Health Survey data were collected from all consenting patients seen within the National Spine Network . Patients with symptoms referable to the cervical spine ( as per their physician ) were included ( n = 1,809 ) . SF-36 scores for all eight scales ( bodily pain ( BP ) , vitality ( VT ) , general health ( GH ) , mental health ( MH ) , physical function ( PF ) , role physical ( RP ) , role emotional ( RE ) , and social function ( SF ) , and two summary scales ( Physical Component Summary [ PCS ] and Mental Component Summary [ MCS ] ) were calculated . Age/gender normative scores were subtracted from the scale scores to produce a negative “ impact ” score , which reflected how far below normal health status these patients were . Patients were grouped according to location of symptoms ( axial only , radicular only , or axial and radicular ) , age ( younger than 40 , 40 to 60 , and older than 60 years ) , and symptom duration ( acute : < 6 wk ; subacute : 6 wk–6 mo ; and chronic : > 6 mo ) . SF-36 scores were compared between all groups using analysis of variance and multiple comparisons with Bonferroni adjustment . Results . Patients who presented with both axial and radicular symptoms had the lowest SF-36 scores relative to age and gender norms . These scores were significantly lower than those for patients with only axial or only radicular symptoms across all eight subscales ( P < 0.05–P < 0.0001 ) . Scores for patients with only axial pain were significantly lower than for patients with only radicular pain for VT ( P < 0.04 ) and GH ( P < 0.004 ) . Patients younger than 40 and those between ages 40 to 60 years were significantly more impacted by their symptoms than patients older than 60 years for all eight scales ( P < 0.01 ) . PCS scores were similar for acute , subacute , and chronic groups , whereas MCS scores were significantly worse for patients with chronic pain . Conclusions . Combined neck and arm pain were much more disabling than either symptom alone . Younger patients ( younger than 40 or 40–60 ) were more affected by these symptoms than patients older than 60 years . In addition , as symptom duration increased , a negative impact on mental health was observed , although chronic symptoms did not affect physical health . This study suggests that patients with a significant component of axial pain in conjunction with cervical radiculopathy should be considered the most affected of all patients with cervical spondylosis . Given the evidence that the treatment methods at the disposal of physicians are effective , this study suggests that prompt treatment of these patients may help avoid the harmful effects of chronic symptoms on mental functioning , especially among younger patients who were found to be more impacted by the symptoms Output:	The findings of this study will assist clinicians who seek to utilise suitable and accurate measures to assess upper limb function for a patient with neck pain .
MS21625	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : To present long-term results of a large series of patients su bmi tted to laparoscopic Roux-en-Y gastric bypass ( RYGBP ) for morbid obesity . Background : Reports on long-term results of RYGBP are scarce and focus primarily on weight loss . Our aim is to provide mid- to long-term data of RYGBP , with detailed results on weight loss , evolution of comorbidities and quality of life , also using the BAROS score . Methods : All patients who underwent a primary RYGBP for morbid obesity in our 2 hospitals between 1999 and August 2008 were included . Data were collected prospect ively in a computerized data base , and review ed for the purpose of this study . Results : A total of 379 patients were included in the analysis of long-term results , 282 women , and 97 men , with a mean BMI of 46.3 kg/m2 . After 5 years , 74.9 % of the patients achieved an excess weight loss of at least 50 % , with a mean of 62.7 % and 76.8 % achieved a BMI < 35 kg/m2 . The corresponding figures after 7 years were 64.9 , 58.1 , and 71.9 , respectively . There was a small but significant long-term weight regain . All comorbidities improved markedly in the vast majority of patients , with no significant difference between the 3- and 5-year terms . Quality of life also improved markedly , and more than 95 % of the patients had a good to excellent 5-year overall result according to the BAROS score . Conclusions : Laparoscopic RYGBP for morbid obesity results in good and maintained weight loss up to 7 years in the majority of patients , improves quality of life and markedly improves all the evaluated comorbidities , result ing in good to excellent overall 5-year results in 97 % of the patients according to the BAROS score Background Aim ing to clarify the mechanism of weight loss after the restrictive bariatric procedure of sleeve gastrectomy ( LSG ) , the volumes and pressures of the stomach , of the removed part , and of the remaining sleeve were measured in 20 morbidly obese patients . Methods The technique used consisted of occlusion of the pylorus with a laparoscopic clamp and of the gastroesophageal junction with a special orogastric tube connected to a manometer . Instillation of methylene-blue-colored saline via the tube was continued until the intraluminal pressure increased sharply , or the inflated stomach reached 2,000 cc . After recording of measurements , LSG was performed . Results Mean volume of the entire stomach was 1,553 cc ( 600–2,000 cc ) and that of the sleeve 129 cc ( 90–220 cc ) , i.e. , 10 % ( 4–17 % ) and that of the removed stomach was 795 cc ( 400–1,500 cc ) . The mean basal intragastric pressure of the whole stomach after insufflations of the abdominal cavity with CO2 to 15 mmHg was 19 mmHg ( 11–26 mmHg ) ; after occlusion and filling with saline it was 34 mmHg ( 21–45 mmHg ) . In the sleeved stomach , mean basal pressure was similar 18 mmHg ( 6–28 mmHg ) ; when filled with saline , pressure rose to 43 mmHg ( 32–58 mmHg ) . The removed stomach had a mean pressure of 26 mmHg ( 12–47 mmHg ) . There were no postoperative complications and no mortality . Conclusions The notably higher pressure in the sleeve , reflecting its markedly lesser distensibility compared to that of the whole stomach and of the removed fundus , indicates that this may be an important element in the mechanism of weight loss BACKGROUND The effect of bariatric surgery on iron absorption is only partially known . OBJECTIVE The objective was to study the effects of sleeve gastrectomy ( SG ) and Roux-en-Y gastric bypass ( RYGBP ) on heme- and nonheme-iron absorption and iron status . DESIGN Fifty-eight menstruating women were enrolled in this prospect i ve study [ mean ( ±SD ) age : 35.9 ± 9.1 y ; weight : 101.7 ± 13.5 kg ; BMI ( in kg/m² ) : 39.9 ± 4.4 ] . Anthropometric , body-composition , dietary , and hematologic indexes and heme- and nonheme-iron absorption-using a st and ardized meal containing 3 mg Fe-were determined before and 12 mo after surgery . Forty-three subjects completed the 12-mo follow-up . Iron supplements were strictly controlled . RESULTS Heme-iron absorption was 23.9 % before and 6.2 % 12 mo after surgery ( P < 0.0001 ) . Nonheme-iron absorption decreased from 11.1 % to 4.7 % ( P < 0.0001 ) . No differences were observed by type of surgery . Iron intakes from all sources of supplements were 27.9 ± 6.2 mg/d in the SG group and 63.2 ± 21.1 mg/d in the RYGBP group ( P < 0.001 ) . Serum ferritin and total-body iron decreased more after RYGBP than after SG . CONCLUSIONS Iron ( heme and nonheme ) absorption is markedly reduced after SG and RYGBP . The magnitude of the decrease in heme-iron absorption is greater than that of nonheme iron . The amounts suggested as iron supplements may need to be increased to effectively prevent iron-status impairment Background Bariatric surgery is currently the most effective treatment for morbid obesity . It provides not only substantial weight loss , but also resolution of obesity-related comorbidities . Laparoscopic sleeve gastrectomy ( LSG ) has rapidly been gaining in popularity . However , there are limited data on the reduction of obesity-related comorbidities for LSG compared to laparoscopic Roux-en-Y gastric bypass ( LRYGB ) . The aim of this study was to assess the effectiveness of laparoscopic LSG versus LRYGB for the treatment of obesity-related comorbidities . Methods A total of 558 patients who underwent either LSG or LRYGB for morbid obesity at the Westchester Medical Center between April 2008 and September 2010 were included . Data were collected prospect ively into a computerized data base and review ed for this study . Fisher ’s exact test analyses compared 30-day , 6-month , and 1-year outcomes of obesity-related comorbidities . Results A total of 558 patients were included in the analysis of obesity-related comorbidity resolution ; 200 underwent LSG and 358 underwent LRYGB . After 1 year , 86.2 % of the LSG patients had one or more comorbidities in remission compared to 83.1 % LRYGB patients ( P = 0.688 ) . With the exception of GERD ( −0.09 vs. 50 % ; P < 0.001 ) , similar comorbidity remission rates were observed between LSG and LRYGB for sleep apnea ( 91.2 vs. 82.8 % ; P = 0.338 ) , hyperlipidemia ( 63 vs. 55.8 % ; P = 0.633 ) , hypertension ( 38.8 vs. 52.9 % ; P = 0.062 ) , diabetes ( 58.6 vs. 65.5 % ; P = 0.638 ) , and musculoskeletal disease ( 66.7 vs. 79.4 % ; P = 0.472 ) . Conclusions Laparoscopic sleeve gastrectomy markedly improves most obesity-related comorbidities . Compared to LRYGB , LSG may have equal in reducing sleep apnea , hyperlipidemia , hypertension , diabetes , and musculoskeletal disease . LRYGB appears to be more effective at GERD resolution than LSG Background The long-term efficacy of laparoscopic Roux-en-Y gastric bypass ( RYGB ) in the treatment of morbid obesity has been demonstrated . Laparoscopic sleeve gastrectomy ( SG ) as a single procedure has shown promising short-term results , but the long-term efficacy of SG has not yet been demonstrated . The aim of this study was to determine the preliminary 30-day morbidity and mortality of RYGB and SG in a prospect i ve multicenter r and omized setting . Methods A total of 240 morbidly obese ( BMI = 35–66 kg/m² ) patients evaluated by a multidisciplinary team were r and omized to undergo either RYGB or SG . There were 117 patients in the RYGB group and 121 in the SG group ; two patients had to be excluded after r and omization . Both study groups were comparable regarding age , gender , BMI , and comorbidities . Results There was no 30-day mortality . The median operating time was significantly shorter in the SG group ( 66 min vs. 94 min , p < 0.001 ) . All complications were recorded thoroughly . There were 7 ( 5.8 % ) major complications following SG and 11 ( 9.4 % ) after RYGB ( p = 0.292 ) . Nine ( 7.4 % ) SG patients and 20 ( 17.1 % ) RYGB patients had minor complications ( p = 0.023 ) . The overall morbidity was 13.2 % after SG and 26.5 % after RYGB ( p = 0.010 ) . There were three ( 2.5 % ) early reoperations after SG and four ( 3.3 % ) after RYGB ( p = 0.719 ) . Conclusions At 30-day analysis SG is associated with a shorter operating time and fewer early minor complications compared to RYGB . There were no significant differences in major complications or early reoperations . Long-term follow-up is required to determine the effect on weight loss , resolution of obesity-related comorbidities , and improvement of quality of life Background : Bariatric surgery is currently the most effective treatment in morbidly obese patients , leading to durable weight loss . Objective : In this prospect i ve double blind study , we aim to evaluate and compare the effects of laparoscopic Roux-en-Y gastric bypass ( LRYGBP ) with laparoscopic sleeve gastrectomy ( LSG ) on body weight , appetite , fasting , and postpr and ial ghrelin and peptide-YY ( PYY ) levels . Methods : After r and omization , 16 patients were assigned to LRYGBP and 16 patients to LSG . Patients were reevaluated on the 1st , 3rd , 6th , and 12th postoperative month . Blood sample s were collected after an overnight fast and in 6 patients in each group after a st and ard 420 kcal mixed meal . Results : Body weight and body mass index ( BMI ) decreased markedly ( P < 0.0001 ) and comparably after either procedure . Excess weight loss was greater after LSG at 6 months ( 55.5 % ± 7.6 % vs. 50.2 % ± 6.5 % , P = 0.04 ) and 12 months ( 69.7 % ± 14.6 % vs. 60.5 % ± 10.7 % , [ P = 0.05 ] ) . After LRYGBP fasting ghrelin levels did not change significantly compared with baseline ( P = 0.19 ) and did not decrease significantly after the test meal . On the other h and , LSG was followed by a marked reduction in fasting ghrelin levels ( P < 0.0001 ) and a significant suppression after the meal . Fasting PYY levels increased after either surgical procedure ( P ≤ 0.001 ) . Appetite decreased in both groups but to a greater extend after LSG . Conclusion : PYY levels increased similarly after either procedure . The markedly reduced ghrelin levels in addition to increased PYY levels after LSG , are associated with greater appetite suppression and excess weight loss compared with LRYGBP Introduction Roux-en-Y gastric bypass ( RYGB ) is considered the gold st and ard bariatric procedure with documented safety and effectiveness . Laparoscopic sleeve gastrectomy ( LSG ) is a newer procedure being done with increasing frequency . R and omized comparisons of LSG and other bariatric procedures are limited . We present the results of the first prospect i ve r and omized trial comparing LSG and RYGB in the Polish population . Aim To assess the efficacy and safety of LSG versus RYGB in the treatment of morbid obesity and obesity-related comorbidities . Material and methods Seventy-two morbidly obese patients were r and omized to RYGB ( 36 patients ) or LSG ( 36 patients ) . Both groups were comparable regarding age , gender , body mass index ( BMI ) and comorbidities . The follow-up period was at least 12 months . Baseline and 6 and 12 month outcomes were analyzed including assessment of percent excess weight lost ( % EWL ) , reduction in BMI , morbidity ( minor , major , early and late complications ) , mortality , reoperations , comorbidities and nutritional deficiencies . Results There was no 30-day mortality and no significant difference Output:	Compared with SG , RYGB had significantly better effect in resolving type 2 diabetes mellitus , hypertension , hypercholesterolemia , gastroesophageal reflux disease , and arthritis . However , RYGB had higher incidence of complications and reoperation , and longer operation time than SG . RYGB was more effective than SG in the resolution of obesity-related comorbidities , SG was a safer procedure with a reduced rate of complications and reoperation
MS21626	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea ( BCNU ) wafers ( Gliadel wafers ) prolong survival in patients with recurrent glioblastoma multiforme . A previously completed phase 3 trial , also placebo controlled , in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers . Because of the small number of patients in that trial , a larger phase 3 trial was performed to confirm these results . Two hundred forty patients were r and omized to receive either BCNU or placebo wafers at the time of primary surgical resection ; both groups were treated with external beam radiation postoperatively . The two groups were similar for age , sex , Karnofsky performance status ( KPS ) , and tumor histology . Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group ( log-rank P -value stratified by country = 0.03 ) , with a 29 % reduction in the risk of death in the treatment group . When adjusted for factors affecting survival , the treatment effect remained positive with a risk reduction of 28 % ( P = 0.03 ) . Time to decline in KPS and in 10/11 neuroperformance measures was statistically significantly prolonged in the BCNU wafer-treated group ( P < /= 0.05 ) . Adverse events were comparable for the 2 groups , except for CSF leak ( 5 % in the BCNU wafer-treated group vs. 0.8 % in the placebo-treated group ) and intracranial hypertension ( 9.1 % in the BCNU wafer-treated group vs. 1.7 % in the placebo group ) . This study confirms that local chemotherapy with BCNU wafers is well tolerated and offers a survival benefit to patients with newly diagnosed malignant glioma The results of a multi-institutional phase I trial evaluating the safety of surgically implanted biodegradable 1,3-bis(chloro-ethyl)-1-nitrosourea ( BCNU ) impregnated polymer as theinitial therapy for malignant brain tumors are reported . This is the first study of locally delivered BCNU and st and ard external beam radiation therapy ( XRT ) given concurrently . Twenty-two patients were treated at three hospitals . The entry criteria were : single unilateral tumor focus larger than 1 cm3 ; age over 18 years ; Karnofsky Performance Score ( KPS ) of at least 60 h ; and an intra-operative diagnosis of malignant glioma . Twenty-one of twenty-two patients had glioblastoma multiforme . After surgery , seven or eight BCNU-loaded polyanhydride polymer discs ( 7.7 mg BCNU each ) were placed in the resection cavity . Postoperatively , all patients received st and ard radiation therapy ; none received additional chemotherapy in the first 6 months . Neurotoxicity , systemic toxicity , and survival were assessed . No perioperative mortality was seen . Neurotoxicity was equivalent to that occurring in other series of patients undergoing craniotomy and XRT without local chemotherapy . Systematic ally , no significant bone marrow suppression occurred , and there were no wound infections . Median survival in this group of older patients ( mean age=60 ) was 42 weeks , 8 patients survived 1 year , and 4 patients survived more than 18 months . Interstitial chemotherapy with BCNU-polymer with subsequent radiation therapy appears to be safe as an initial therapy . Several long-term survivors in this group of older patients with predominantly glioblastoma suggests efficacy in some patients . Dose escalation and efficacy trials are planned to further evaluate interstitial chemotherapy for the initial treatment of malignant gliomas OBJECTIVE To find out the effect of carmustine ( bischloroethyl-nitrosourea ) combined with a biodegradable polymer in the treatment of malignant ( Grade s III and IV ) gliomas , applied locally , at the time of the primary operation . METHODS Prospect i ve , r and omized double-blind study of an active treatment group versus a placebo group . Conducted at the Departments of Neurosurgery of the University Hospitals of Helsinki , Tampere , and Turku in Finl and and Trondheim in Norway . The study consisted of 32 patients ( 16 in each treatment group ) enrolled between March 23 , 1992 , and March 19 , 1993 . The study was planned to include 100 patients but had to be terminated prematurely , because the drug that was being used had become unobtainable . The main outcome measures included the survival times of patients after the operations and the application of an active drug or placebo . RESULTS The median time from surgery to death was 58.1 weeks for the active treatment group versus 39.9 weeks for the placebo group ( P = 0.012 ) . For 27 patients with Grade IV tumors , the corresponding times were 39.9 weeks for the placebo group and 53.3 weeks for the active treatment group ( P = 0.008 ) . At the end of the study , six patients were still alive , five of whom belonged to the active treatment group . CONCLUSION Carmustine applied locally in a biodegradable polymer at the time of primary operation , seems to have a favorable effect on the life span of patients with high- grade gliomas PURPOSE This New Approaches to Brain Tumor Therapy CNS Consortium study sought to determine the maximum-tolerated dose ( MTD ) of carmustine ( BCNU ) that can be implanted in biodegradable polymers following resection of recurrent high- grade gliomas and the systemic BCNU exposure with increasing doses of interstitial BCNU . PATIENTS AND METHODS Forty-four adults underwent tumor debulking and polymer placement . Six patients per dose level were studied using polymers with 6.5 % , 10 % , 14.5 % , 20 % , and 28 % BCNU by weight . Toxicities were assessed 1 month after implantation by a safety monitoring committee to determine whether subsequent escalations should occur . Nine additional patients were studied at the MTD to confirm safety . BCNU blood levels were obtained before and after polymer implantation . RESULTS No dose-limiting toxicities were identified at the 6.5 % , 10 % , or 14.5 % dose levels , although difficulties with wound healing , seizures , and brain edema were noted . At the 20 % dose , these effects seemed more prominent , and six additional patients were treated at this dose and tolerated treatment well . Three of four patients receiving the 28 % polymers developed severe brain edema and seizures , and accrual to this cohort was stopped . Nine additional patients received 20 % polymer , confirming this as the MTD . Maximum BCNU plasma concentrations with the 20 % loaded polymers were 27 ng/mL. Overall median survival was 251 days . CONCLUSION The MTD of BCNU delivered in polymer to the surgical cavity is 20 % . This polymer provides five times more BCNU than st and ard commercially available BCNU polymers and results in minimal systemic BCNU exposure . Additional studies are needed to establish the efficacy of high-dose BCNU polymers OBJECTIVE To determine the risks and survival benefit associated with implantation of an absorbable , 1,3-bis(2chloroethyl)-1-nitrosourea-impregnated polymer wafer , we prospect ively studied patients with recurrent glioblastoma multiforme and compared them with a demographically matched cohort group . METHODS Over a 29-month period , 62 patients underwent operations . All had tumor growth despite st and ard treatment , a Karnofsky performance score of > or = 70 , and histopathological confirmation of glioblastoma . Seventeen patients underwent gross total resection with placement of 1,3-bis(2-chloroethyl)-1-nitrosourea wafers ( wafer group ) at a median 44 weeks from diagnosis ( 6 women , 11 men ; median age , 56 years ) . A cohort group of 45 patients undergoing surgery for recurrent glioblastoma during the same time period , but not receiving wafers , was identified . Surgery was performed at a median 47 weeks from diagnosis ( 14 women , 31 men ; median age , 54 years ) . RESULTS Within 6 weeks of surgery , 13 complications were identified in 8 patients in the wafer group . In the cohort group , 6 patients sustained 8 complications . We were unable to identify any survival advantage using Kaplan-Meier analysis . In the wafer group , median survival was 58 weeks from diagnosis and 14 weeks from wafer implantation . In the cohort group , median survival was 97 weeks from diagnosis and 50 weeks from operation . CONCLUSION 1,3-bis(2-chloroethyl)-1-Nitrosourea wafer implantation for recurrent glioblastoma was associated with a higher risk of postoperative complications , particularly those related to infection and wound healing . No clear survival benefit associated with wafer implantation was identified Malignant gliomas have been difficult to treat with chemotherapy . The most effective agent , BCNU ( carmustine ) , has considerable systemic toxicity and a short half-life in serum . To obviate these problems , a method has been developed for the local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers . Implantation of the drug-impregnated polymer at the tumor site allows prolonged local exposure with minimal systemic exposure . In this Phase I-II study , 21 patients with recurrent malignant glioma were treated with BCNU released interstitially by means of a polyanhydride biodegradable polymer implant . Up to eight polymer wafers were placed in the resection cavity intraoperatively , upon completion of tumor debulking . The polymer releases the therapeutic drug for approximately 3 weeks . Three increasing concentrations of BCNU were studied ; the treatment was well tolerated at all three levels . There were no adverse reactions to the BCNU wafer treatment itself . The average survival period after reoperation was 65 weeks for the first dose group , 64 weeks for the second dose group , and 32 weeks for the highest dose group . The overall mean survival time was 48 weeks from reoperation and 94 weeks from the original operation . The overall median survival times were 46 weeks postimplant and 87 weeks from initial surgery . Eighteen ( 86 % ) of 21 patients lived more than 1 year from the time of their initial diagnosis and eight ( 38 % ) of 21 patients lived more than 1 year after intracranial implantation of the polymer . Frequent hematology , blood chemistry , and urinalysis tests did not reveal any systemic effect from this interstitial chemotherapy . Since the therapy is well tolerated and safe , a placebo-controlled clinical trial has been started . The trial will measure the effect of the second treatment dose on survival of patients with recurrent malignant glioma Output:	CONCLUSIONS Gliadel is an option for selected patients with newly diagnosed malignant glioma where a near gross total resection is possible . Gliadel is also an option for patients with surgically resectable recurrent malignant glioma
MS21627	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE The aim was to examine the effects of a Mindfulness-Based Stress Reduction ( MBSR ) intervention on cardiovascular and cortisol activity during acute stress . METHOD Eighty-eight healthy community-dwelling individuals reporting elevated stress levels were r and omly assigned to the MBSR protocol or a waitlist control group . Before and after the intervention period they participated in a laboratory stress protocol consisting of mental arithmetic and speech tasks . Laboratory measurements included continuous cardiovascular parameters ( heart period , heart rate variability , and systolic and diastolic blood pressure [ SBP and DBP ] ) , and salivary cortisol . RESULTS Compared to the control group and controlling for age , sex , body mass index , and beta-blockers , the MBSR group showed larger pre- to postintervention decreases in overall SBP ( F(1 , 58 ) = 4.99 , p = .029 , partial η² = .08 ) and DBP ( F(1 , 58 ) = 11.09 , p = .002 , partial η² = .16 ) . In addition , the MBSR group exhibited smaller SBP and DBP stress-related changes from pre- to postintervention ( F(2 , 116 ) = 4.89 , p = .012 , partial η² = .08 ; F(2 , 116 ) = 6.07 , p = .007 , partial η² = .10 , respectively ) . No effects were obtained on other physiological measures . CONCLUSION MBSR may help reducing blood pressure levels and blood pressure reactivity to stress OBJECTIVE Emotional distress is common in out patients with diabetes , affecting ∼20–40 % of the patients . The aim of this study was to determine the effectiveness of group therapy with Mindfulness-Based Cognitive Therapy ( MBCT ) , relative to usual care , for patients with diabetes with regard to reducing emotional distress and improving health-related quality of life and glycemic control . RESEARCH DESIGN AND METHODS In the present r and omized controlled trial , 139 out patients with diabetes ( type 1 or type 2 ) and low levels of emotional well-being were r and omized to MBCT ( n = 70 ) or a waiting list group ( n = 69 ) . Primary outcomes were perceived stress ( Perceived Stress Scale ) , anxiety and depressive symptoms ( Hospital Anxiety and Depression Scale ) , mood ( Profiles of Mood States ) , and diabetes-specific distress ( Problem Areas In Diabetes ) . Secondary outcomes were health-related quality of life ( 12-Item Short-Form Health Survey ) , and glycemic control ( HbA1c ) . Assessment s were conducted at baseline and at 4 and 8 weeks of follow-up . RESULTS Compared with control , MBCT was more effective in reducing stress ( P < 0.001 , Cohen d = 0.70 ) , depressive symptoms ( P = 0.006 , d = 0.59 ) , and anxiety ( P = 0.019 , d = 0.44 ) . In addition , MBCT was more effective in improving quality of life ( mental : P = 0.003 , d = 0.55 ; physical : P = 0.032 , d = 0.40 ) . We found no significant effect on HbA1c or diabetes-specific distress , although patients with elevated diabetes distress in the MBCT group tended to show a decrease in diabetes distress ( P = 0.07 , d = 0.70 ) compared with the control group . CONCLUSIONS Compared with usual care , MBCT result ed in a reduction of emotional distress and an increase in health-related quality of life in diabetic patients who had lower levels of emotional well-being Objective Mindfulness-based stress reduction ( MBSR ) is an increasingly popular practice demonstrated to alleviate stress and treat certain health conditions . MBSR may reduce elevated blood pressure ( BP ) . Treatment guidelines recommend life-style modifications for BP in the prehypertensive range ( systolic BP [ SBP ] 120–139 mm Hg or diastolic BP [ DBP ] 80–89 mm Hg ) , followed by antihypertensives if BP reaches hypertensive levels . MBSR has not been thoroughly evaluated as a treatment of prehypertension . A r and omized clinical trial of MBSR for high BP was conducted to determine whether BP reductions associated with MBSR exceed those observed for an active control condition consisting of progressive muscle relaxation ( PMR ) training . Methods Fifty-six men ( 43 % ) and women ( 57 % ) averaging ( st and ard deviation ) 50.3 ( 6.5 ) years of age ( 91 % white ) with unmedicated BP in the prehypertensive range were r and omized to 8 weeks of MBSR or PMR delivered in a group format . Treatment sessions were administered by one treatment provider and lasted approximately 2.5 hours each week . Clinic BP was the primary outcome measure . Ambulatory BP was a secondary outcome measure . Results Analyses were based on intent to treat . Patients r and omized to MBSR exhibited a 4.8-mm Hg reduction in clinic SBP , which was larger than the 0.7-mm Hg reduction observed for PMR ( p = .016 ) . Those r and omized to MBSR exhibited a 1.9-mm Hg reduction in DBP compared with a 1.2-mm Hg increase for PMR ( p = .008 ) . MBSR did not result in larger decreases in ambulatory BP than in PMR . Conclusions MBSR result ed in a reduction in clinic SBP and DBP compared with PMR . Trial Registration Clinical Trials.gov identifier : NCT00440596 Hypertension affects a large proportion of urban African-American older adults . While there have been great strides in drug development , many older adults do not have access to such medicines or do not take them . Mindfulness-based stress reduction ( MBSR ) has been shown to decrease blood pressure in some population s. This has not been tested in low-income , urban African-American older adults . Therefore , the primary purpose of this pilot study was to test the feasibility and acceptability of a mindfulness-based program for low income , minority older adults provided in residence . The secondary purpose was to learn if the mindfulness-based program produced differences in blood pressure between the intervention and control groups . Participants were at least 62 years old and residents of a low-income senior residence . All participants were African-American , and one was male . Twenty participants were r and omized to the mindfulness-based intervention or a social support control group of the same duration and dose . Blood pressure was measured with the Omron automatic blood pressure machine at baseline and at the end of the 8-week intervention . A multivariate regression analysis was performed on the difference in scores between baseline and post-intervention blood pressure measurements , controlling for age , education , smoking status , and anti-hypertensive medication use . Effect sizes were calculated to quantify the magnitude of the relationship between participation in the mindfulness-based intervention and the outcome variable , blood pressure . Attendance remained > 80 % in all 8 weeks of both the intervention and the control groups . The average systolic blood pressure decreased for both groups post-intervention . Individuals in the intervention group exhibited a 21.92-mmHg lower systolic blood pressure compared to the social support control group post-intervention and this value was statistically significant ( p = 0.020 ) . The average diastolic blood pressure decreased in the intervention group post-intervention , but increased in the social support group . Individuals in the intervention group exhibited a 16.70-mmHg lower diastolic blood pressure compared to the social support group post-intervention , and this value was statistically significant ( p = 0.003 ) . Older adults are at a time in life when a reflective , stationary intervention , delivered in residence , could be an appealing mechanism to improve blood pressure . Given our preliminary results , larger trials in this hypertensive study population are warranted CONTEXT Psychological distress is linked with impaired glycemic control among diabetics . OBJECTIVE Estimate changes in glycemic control , weight , blood pressure , and stress-related psychological symptoms in patients with type 2 diabetes participating in a st and ard Mindfulness Based Stress Reduction ( MBSR ) program . DESIGN Prospect i ve , observational study . SETTING Academic health center . PATIENTS Adult patients with type 2 diabetes mellitus . INTERVENTIONS Participation in MBSR program for heterogeneous patient population . Diet and exercise regimens held constant . MAIN OUTCOME MEASURES Glycosylated hemoglobin A1c ( HA1c ) , blood pressure , body weight , and Symptom Checklist 90-Revised ( anxiety , depression , somatization , and general psychological distress scores ) . RESULTS Eleven of 14 patients completed the intervention . At 1 month follow-up , HA1c was reduced by 0.48 % ( P = .03 ) , and mean arterial pressure was reduced by 6 mmHg ( P = .009 ) . Body weight did not change . A decrease in measures of depression , anxiety , and general psychological distress was observed OBJECTIVE To determine whether a mindfulness-based stress reduction ( MBSR ) intervention is effective for reducing psychosocial distress ( i.e. , depression , psychosocial stress ) and the progression of nephropathy ( i.e. , albuminuria ) and for improving the subjective health status of patients with type 2 diabetes . RESEARCH DESIGN AND METHODS Patients with type 2 diabetes and microalbuminuria were r and omized to a mindfulness-based intervention ( n = 53 ) or a treatment-as-usual control ( n = 57 ) group . The study is design ed to investigate long-term outcomes over a period of 5 years . We present data up to the first year of follow-up ( FU ) . RESULTS At FU , the MBSR group showed lower levels of depression ( d = 0.71 ) and improved health status ( d = 0.54 ) compared with the control group . No significant differences in albuminuria were found . Per- protocol analysis also showed higher stress reduction in the intervention group ( d = 0.64 ) . CONCLUSIONS MBSR intervention achieved a prolonged reduction in psychosocial distress . The effects on albuminuria will be followed up further Summary : Heart disease is the leading cause of death among Americans each year , yet the misperception still exists that cardiovascular disease is not a serious health problem for women . Evidence indicates that anxiety contributes to the development of heart disease . The primary purpose of this study was to assess the effectiveness of Kabat-Zinn 's mindfulness-based stress reduction program to reduce anxiety in women with heart disease . Anxiety , emotional control , coping styles , and health locus of control were compared in a treatment and control group of women with heart disease . Post-intervention analyses provide initial support for beneficial effects of this program In this study effects of a brief mindfulness-based stress reduction intervention were examined in cardiac patients who had a percutaneous coronary intervention ( PCI ) . One-hundred- and -fourteen patients ( mean age 55 ± 7 years , 18 % women ) were r and omly assigned to a 4-session mindfulness group intervention or a minimal mindfulness self-help control group that received a booklet containing identical information . Compared to self-help , the group intervention showed larger increases in psychological and social quality of life ( p < .05 , partial η2 = .04 and .05 , respectively ) . For symptoms of anxiety and depression , and for perceived stress , this effect was evident only in patients younger than 60 years ( p < .01 , partial η2 = .10 and .15 , respectively ) . These effects were partially or fully mediated by increase in mindfulness . The brief group mindfulness intervention seems beneficial for cardiac PCI patients regarding general psychosocial quality of life , although for specific psychological symptoms , this intervention can be recommended only for nonelderly patients OBJECTIVE Stress has been cited as a causal factor in heart disease . The objective of this study was to examine the effects of an 8-week mindfulness-based stress-reduction program on the resting levels of stress hormones , physical functioning , and submaximal exercise responses in women with heart disease . SUBJECTS R and om selection with the numbers 1 and 2 were used to assign 18 women ( 60 + /-6.3 years old ) with documented histories of heart disease to a treatment group ( n = 9 ) or a control group ( n = 9 ) . Speilberger 's state anxiety scores for the treatment ( M = 37.88 ; st and ard deviation ( SD ) = 10.91 ) and control group ( M = 43.22 ; SD = 12.26 ) were not significantly different prior to the start of the study . However , their scores fell in the upper percentile rank for normal adults in their age category . INTERVENTION The intervention was provided one night each week for 2 hours over a period of 8 weeks . The intervention included didactic , inductive , and experiential modes of learning regarding stress responses and mindfulness skill-development training . DESIGN Pre-post test hormonal measurements and physical function were analyzed using a 2 ( group ) by 2 ( time ) analysis of variance ( ANOVA ) with repeated measures following the 8-week program . Submaximal exercise responses were also compared between the treatment group and the control group following the 8-week program . A 2 ( group ) by 3 ( time ) ANOVA with repeated measures was used to analyze the data . SETTING S/LOCATION Weekly meetings were held on a university medical school campus . Submaximal exercise responses were recorded while participants cycled on a stationary bike in an applied physiology laboratory following the 8-week program . RESULTS There were no significant main effects Output:	Whilst population s with vascular disease appear to derive a range of psychological benefits from MBSR/MBCT intervention , the effects on physical parameters of disease are not yet established .
MS21628	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE The study evaluated whether targeted changes in factors influencing enjoyment of physical education ( PE ) , physical activity enjoyment , and self-efficacy beliefs about participating in physical activity mediated the effect of the Lifestyle Education for Activity Program ( LEAP ) intervention on participation in physical activity . METHODS High schools ( N=24 ) paired on enrollment size , racial composition , urban or rural location , and class structure were r and omized into control ( N=12 ) or experimental ( N=12 ) groups . Of the 4044 girls enrolled and eligible , 2087 ( 51.6 % ) participated in the measurement component of the study . There were 1038 girls in the control group and 1049 girls in the experimental group . INTERVENTION LEAP was a comprehensive school-based intervention emphasizing changes in instruction and school environment design ed to increase physical activity among black and white adolescent girls . It was organized according to the Coordinated School Health Program and included a PE component with core objectives of promoting enjoyment of PE , physical activity enjoyment , and self-efficacy . RESULTS Latent variable structural equation modeling indicated that : 1 ) the intervention had direct , positive effects on physical activity and factors influencing enjoyment of PE , which subsequently explained the effects of increased physical activity enjoyment and self-efficacy on increased physical activity ; and 2 ) an additional , indirect effect of physical activity enjoyment on physical activity operated by an influence on self-efficacy . CONCLUSIONS Increases in enjoyment partially mediated the positive effect of the LEAP intervention . To our knowledge , we have provided the first experimental evidence from a r and omized controlled trial linking increased enjoyment with increased physical activity among black and white adolescent girls The primary objective of this pilot study was to evaluate the effect of active video games on children 's physical activity levels . Twenty children ( mean ± SD age = 12 ± 1.5 years ; 40 % female ) were r and omised to receive either an active video game up grade package or to a control group ( no intervention ) . Effects on physical activity over the 12-week intervention period were measured using objective ( Actigraph accelerometer ) and subjective ( Physical Activity Question naire for Children [ PAQ-C ] ) measures . An activity log was used to estimate time spent playing active and non-active video games . Children in the intervention group spent less mean time over the total 12-week intervention period playing all video games compared to those in the control group ( 54 versus 98 minutes/day [ difference = -44 minutes/day , 95 % CI [ -92 , 2 ] ] , p = 0.06 ) . Average time spent in all physical activities measured with an accelerometer was higher in the active video game intervention group compared to the control group ( difference at 6 weeks = 194 counts/min , p = 0.04 , and at 12 weeks = 48 counts/min , p = 0.06).This preliminary study suggests that playing active video games on a regular basis may have positive effects on children 's overall physical activity levels . Further research is needed to confirm if playing these games over a longer period of time could also have positive effects on children 's body weight and body mass index . Trial Registration Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists OBJECTIVE We examined the feasibility of Dance Dance Revolution ( DDR ) , a dance video game , in participants ' homes , to increase physical activity ( PA ) and to decrease sedentary screen time ( SST ) . METHODS AND PROCEDURES Sixty children ( 7.5 + /- 0.5 years ) were r and omized in a 2:1 ratio to DDR or to wait-list control ( 10-week delay ) . DDR use was logged , PA was measured objective ly by accelerometry . SST was self-reported at weeks 0 and 10 . At week 28 , after both groups had access to DDR , accelerometry and SST were repeated . RESULTS Mean use of DDR was 89 + /- 82 ( range 0 - 660 min ) min per week ( mpw ) . The DDR group showed increased vigorous PA and a reduction in light PA ; the control group showed no increase in moderate and /or vigorous PA ( MVPA ) although they also had a reduction in light PA . Differences between the groups were not observed . The DDR group also reported a decrease in SST of -1.2 + /- 3.7 h per week ( hpw ) ( P < 0.05 ) , whereas the controls reported an increase of + 3.0 + /- 7.7 hpw ( nonsignificant ) . The difference in SST between the groups was significant , with less SST in the DDR group . Between weeks 10 and 28 , numeric reductions in SST were reported in both groups . In the DDR group , SST at week 28 ( 8.8 + /- 6.0 hpw ) was lower than baseline ( 10.5 + /- 5.5 hpw ; P < 0.03 ) . DISCUSSION This pilot study suggests that DDR reduces SST and may facilitate slight increases in vigorous PA . Further study is needed to better characterize children and context s in which DDR may promote a healthy lifestyle The purpose of this pilot study was to evaluate the effect of a weekly multiplayer class on the motivation of children aged 9 - 12 years to play an interactive dance simulation video game ( IDSVG ) at home over a period of 12 weeks . A sample of 27 children was r and omly assigned to ( 1 ) a home group instructed to play the IDSVG at home ; ( 2 ) a multiplayer group instructed to play the IDSVG at home and to participate in a weekly IDSVG multiplayer class . Participants were asked to play the IDSVG as often as they liked and report the playing time daily on a calendar for a 12-week period . Motivation to play was assessed by the playing duration of IDSVG in minutes and the dropout during the study . Mean age of the 16 children who completed the study was 10.6+/-0.8 years . During the 12-week intervention period , the multiplayer group played approximately twice as many minutes ( 901min ) as the home group ( 376min , p=0.13 ) . Dropout was significantly ( p=0.02 ) lower in the multiplayer group ( 15 % ) than in the home group ( 64 % ) . Our findings suggest that multiplayer classes may increase children 's motivation to play interactive dance simulation video games PURPOSE The primary aim was to determine the energy expenditure ( EE : kcal.kg(-1).h(-1 ) ) in terms of caloric cost and metabolic equivalents of activities commonly performed by children and adolescents . Secondary aims were to determine at what age and pubertal developmental stage values approach those of adults . METHODS In this descriptive study , 295 volunteer youth 8 - 18 yr of age completed 18 common physical activities ( including rest ) while EE was measured continuously with a portable metabolic system . Three sets of activities were assigned in r and om order for each subject . Activities ranged from television viewing and video game play to running and rope skipping . Pubertal development was estimated from a self-report question naire . RESULTS At rest , VO(2 ) and EE were highest in the youngest children and decreased with advancing age and higher pubertal stage in both genders . The age-adjusted and puberty-adjusted energy expenditure values were generally lower than the compendium MET values for sedentary and moderate activities but were more varied for high-intensity activities . However , the ratio of activity EE to REE was comparable in children and adults . CONCLUSIONS Energy expenditure per kilogram of body mass at rest or during exercise is greater in children than adults and varies with pubertal status , thus using the definition of a MET in the compendium of physical activities without adjustment is inadequate for energy estimation in children , until a child reaches Tanner Stage 5 . However , the ratio of activity EE to resting EE in children appears to be similar or slightly less than in the compendium , suggesting that the compendium MET increments used with our adjusted EE values more closely approximate the true EE of activities in children than present adult norms Output:	AVGs are capable of generating EE in youth to attain PA guidelines . Few studies have assessed sustainability of AVG play , which appears to diminish after a short period of time for most players .
MS21629	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND PURPOSE Hyperglycemia at the time of ischemic stroke is associated with increased mortality and morbidity . Animal studies suggest that infa rct expansion may be responsible . The influence of persisting hyperglycemia after stroke has not previously been examined . We measured the blood glucose profile after acute ischemic stroke and correlated it with infa rct volume changes using T2- and diffusion-weighted MRI . METHODS We recruited 25 subjects within 24 hours of ischemic stroke symptoms . Continuous glucose monitoring was performed with a glucose monitoring device ( CGMS ) , and 4-hour capillary glucose levels ( BGL ) were measured for 72 hours after admission . MRI and clinical assessment s were performed at acute ( median , 15 hours ) , subacute ( median , 5 days ) , and outcome ( median , 85 days ) time points . RESULTS Mean CGMS glucose and mean BGL glucose correlated with infa rct volume change between acute and subacute diffusion-weighted MRI ( r > or=0.60 , P<0.01 ) , acute and outcome MRI ( r=0.56 , P=0.01 ) , outcome National Institutes of Health Stroke Scale ( NIHSS ; r > or=0.53 , P<0.02 ) , and outcome modified Rankin Scale ( mRS ; r > or=0.53 , P=0.02 ) . Acute and final infa rct volume change and outcome NIHSS and mRS were significantly higher in patients with mean CGMS or mean BGL glucose > or=7 mmol/L. Multiple regression analysis indicated that both mean CGMS and BGL glucose levels > or=7 mmol/L were independently associated with increased final infa rct volume change . CONCLUSIONS Persistent hyperglycemia on serial glucose monitoring is an independent determinant of infa rct expansion and is associated with worse functional outcome . There is an urgent need to study normalization of blood glucose after stroke BACKGROUND diabetes mellitus not only increases the risk of ischaemic stroke two- to four-fold but also adversely inXuences prognosis . The prevalence of recognised diabetes mellitus in acute stroke patients is between 8 and 20 % , but between 6 and 42 % of patients may have undiagnosed diabetes mellitus before presentation . Post-stroke hyperglycaemia is frequent and of limited diagnostic value and the oral glucose tolerance test assumes that the patient is clinical ly stable and eating normally . There is a need for a simple and reliable method to predict new diabetes mellitus in acute stroke patients . OBJECTIVES to determine the prevalence of unrecognised diabetes mellitus and impaired glucose tolerance on hospital admission and 12 weeks later in acute stroke patients with post-stroke hyperglycaemia > or = 6.1 mmol/l . To measure the accuracy of hyperglycaemia and elevated glycosylated haemoglobin concentration in predicting the presence of unrecognised diabetes mellitus at 12 weeks . DESIGN acute ( < 24 hours ) stroke patients ( cerebral infa rct ion and primary intracerebral haemorrhage ) with admission hyperglycaemia between 6.0 and 17 mmol/l and without a previous history of insulin-treated diabetes mellitus who were r and omised into the Glucose Insulin in Stroke Trial between October 1997 and May 1999 were studied . The Glucose Insulin in Stroke Trial is a r and omised controlled trial investigating the benefits of maintaining euglycaemia in acute stroke patients with mild to moderate hyperglycaemia . At 12 weeks , survivors underwent a 75 g oral glucose tolerance test . The positive predictive value and negative predictive value of admission plasma glucose > or = 6.1 mmol/l and elevated glycosylated haemoglobin concentration in predicting the presence of diabetes mellitus were used to estimate the prevalence of unrecognised diabetes mellitus in a consecutive series of 582 acute stroke admissions . RESULTS 582 consecutive acute stroke patients were assessed for eligibility for the Glucose Insulin Stroke Trial , of whom 83 ( 14 % ) had recognised diabetes mellitus . One hundred and forty-two patients were r and omised and 62 underwent a 3-month oral glucose tolerance test , of whom 26 ( 42 % ) had normal glucose tolerance , 23 ( 37 % ) had impaired glucose tolerance and 13 ( 21 % ) had diabetes mellitus . Admission plasma glucose > or = 6.1 mmol/l and glycosylated haemoglobin > or = 6.2 % predicted the presence of previously unrecognised diabetes mellitus at 12 weeks with a positive predictive value of 80 % and negative predictive value of 96 % . The estimated prevalence of unrecognised diabetes mellitus in the total series of acute stroke admissions was 16 - 24 % . CONCLUSIONS one-third of all acute stroke patients may have diabetes mellitus . For patients presenting with post-stroke hyperglycaemia , impaired glucose tolerance or diabetes mellitus is present in two-thirds of survivors at 12 weeks . Admission plasma glucose > or = 6.1 mmol/l combined with glycosylated haemoglobin > or = 6.2 % are good predictors of the presence of diabetes mellitus following stroke In a prospect i ve study to correlate admission glucose level with neurologic outcome in stroke , 252 acute stroke patients without prior disability and admitted within 24 hours of onset of ictus were assessed . The stroke was classified into one of three types -- cortical infa rct , lacunar infa rct , or intracerebral hemorrhage -- by clinical , computed tomographic , and necropsy findings . Fifty-one diabetic patients were excluded from the entire cohort to form a nondiabetic category for analysis . We found that admission glucose level showed a significantly higher degree of correlation with mortality and morbidity ( measured as arm function , leg function , and activities of daily living ) when cortical ( n = 118 ) and lacunar ( n = 58 ) infa rcts were pooled compared with when they were assessed separately . For intracerebral hemorrhage ( n = 76 ) , admission glucose level correlated with mortality but not morbidity . This trend persisted despite exclusion of diabetic patients . These results are consistent with previous observations of a correlation between a high admission glucose level and the severity of stroke . The importance of segregating cortical from lacunar infa rcts , two groups with a different natural history and prognosis , in any future analysis is emphasized From August 1987 through December 1989 all consecutive conscious patients younger than 70 years with a recent ( less than 48 h ) brain infa rct ion of the carotid territory were prospect ively included in the study . Blood sample s for fasting blood glucose and glycosylated haemoglobin ( HbA1c ) were taken after a median delay of 23 h of the onset of symptoms . The severity of hemiparesis was assessed on admission , at 1 week , 3 weeks , and 3 months . The functional outcome was assessed at 3 months . Computed cerebral tomography was performed on admission , and later on at 3 weeks or 3 months . The brain infa rct volume was measured from the CTs . The patients were diagnosed to have prestroke normoglycemia ( n = 76 ) and prestroke hyperglycemia ( n = 23 ) on basis of the HbA1c level . The case fatality rate , severity of hemiparesis , functional outcome , and infa rct size did not differ between these 2 groups . On the other h and , fasting blood glucose level of the non-diabetics correlated strongly with the severity of hemiparesis and predicted stroke outcome . A statistically significant correlation was observed between blood glucose values and the volumes of cortical infa rcts in non-diabetics . Because prestroke blood glucose level , in contrast to post-stroke blood glucose level , did not have any predictive value concerning stroke outcome it is concluded that high fasting blood glucose values after stroke reflect a stress response to a more severe ischemic brain lesion BACKGROUND The adrenal glucocorticoid stress response in humans causes catabolism , increasing blood glucose and heart rate , and possibly potentiates ischaemic damage to neurons . These effects could induce secondary brain damage in acute stroke . MATERIAL S AND METHODS This prospect i ve study was based on a single determination of s-cortisol in 172 patients included within 24 h of stroke onset , 50 % within 12 h of stroke onset . All patients were admitted to hospital within 6 h of stroke onset . We investigated the relations of s-cortisol to neurological deficit measured by Sc and inavian Stroke Scale ( SSS ) , lesion volume on CT-scan , blood glucose on admission , pulse rate , blood pressure , body temperature , deteriorating stroke , cytokines and cytokine receptors , and outcome . RESULTS In a multivariate logistic regression analysis , s-cortisol was independently related to death within 7 days of stroke onset , odds ratio ( OR ) Cortisol(+100 nmol/l ) 1.9 ( 95 % CI 1.01 - 3.8 ) ; serum-cortisol was , however , not a predictor of death or dependency within 3 months . S-cortisol correlated to SSS ( rho=-0.45 , p<0.001 ) , body temperature ( rho=0.27 , p<0.001 ) , pulse rate ( rho=0.26 , p<0.001 ) , and lesion volume ( rho=0.33 , p<0.001 ) . S-cortisol was related to the presence of insular damage . CONCLUSION Acute stroke mortality related to increasing serum-cortisol levels . S-cortisol was associated with stroke severity and markers reflecting stroke severity Background Screening for undiagnosed diabetes in patients with acute myocardial infa rct ion is recommended ( ESC and EASD Task Force 2007 ) . Glucose tolerance testing in the peri-infa rct period may not be valid because of confounding , e.g. by the acute stress reaction . The aim was to evaluate undiagnosed diabetes ( DM ) and impaired glucose regulation ( IGR ) in AMI during hospital stay and 3 months after discharge . Material s and methods In 96 consecutively admitted AMI patients ( Heart Center Wuppertal , Germany ) OGTT were performed , of whom in 62 OGTT were also carried out 3 months later . Results Before discharge 32 % of the patients had newly diagnosed diabetes and 47 % patients had prediabetes ( IGR ) . Glucose tolerance was normal in 20 ( 21 % ) patients only . After 3 months , 74 % with newly diagnosed DM at baseline still had disturbed glucose metabolism ( 58 % DM , 16 % IGT ) . No patient with normal OGTT became diabetic after 3 months . In multivariate regression , the odds of having diabetes ( 3 months ) was about sixfold higher when having diabetes before discharge ( OGTT ) . Admission glucose , infa rct ion size CKMAX , and inflammation ( CRP ) were not significantly related to OGTT results . Conclusions This prospect i ve study confirms a high prevalence of undiagnosed DM in patients with AMI . In about 60 % of AMI patients , newly diagnosed DM persisted after 3 months . For the first time we could show that there is no correlation between infa rct ion size and undiagnosed diabetes . Thus , an OGTT performed before discharge may provide a reliable measure of disturbed glucose regulation but needs to be repeated AIMS To assess the cardiovascular disease ( CVD ) risk of people with screen-detected Type 2 diabetes and to estimate the risk reduction achievable through early intensive pharmacological intervention . METHODS In ADDITION-Cambridge , diabetic patients were identified among people aged 40 - 69 years through a stepwise screening procedure including a risk score , r and om and fasting capillary blood glucose , HbA(1c ) and oral glucose tolerance test . In those without prior macrovascular disease , 10-year CVD risk was computed using UK Prospect i ve Diabetes Study ( UKPDS ) and Framingham engines . The absolute risk reduction achievable and its plausible range were predicted using relative risk reductions for individual therapies from published trials and sensitivity analysis . RESULTS Of the 867 individuals with undiagnosed diabetes , 19 % had pre-existing CVD , 97 % were overweight or obese , 86 % had hypertension , 75 % had dyslipidaemia , 20 % had microalbuminuria and 18 % were smokers . Of those with hypertension , 35 % were not prescribed drugs and 42 % were suboptimally treated . Of participants with dyslipidaemia , 68 % were not prescribed medications and 22 % were poorly controlled . Median 10-year CVD risk was 34.0%[interquartile range ( IQR ) 26.2 - 44.6 ] in men and 21.5 % ( IQR 15.7 - 28.7 ) in women using the UKPDS engine ; 38.6 % ( IQR 27.8 - 53.0 ) in men and 24. Output:	In this study hyperglycaemia in the setting of an acute stroke was transient in the majority of patients
MS21630	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : Previous studies have described that pediatric offices are ill-prepared for medical emergencies . Pediatric " mock codes " have been utilized to increase the emergency preparedness of inpatient medical units for several decades . These practice drills have been shown to both increase practitioners ' confidence and decrease anxiety during actual resuscitations . Although the use of mock codes is recommended in the outpatient setting , these benefits have yet to be demonstrated for office-based practitioners . Objective : We conducted this study to determine whether mock codes performed in pediatric primary care offices increase practitioner confidence to perform life-saving skills . Methods : Pediatric group practice s participated in a clinical trial of an office-based , 2-step , emergency preparedness training . First , physicians and staffs attended a 1-hour didactic program which included staff education , office emergency protocol s , emergency equipment and medications , and guidelines on instituting a mock code program . Second , each practice participated in a 10 - 15-minute mock code exercise . The drill was conducted by pediatric advanced life support instructors . After the code , a 30-minute feedback session was conducted which review ed office coordination , individual skill performance , and approach to resuscitation . Each participating practice also received an infant manikin and a text complete with several mock codes scenarios written specifically for the pediatric primary care office . Evaluation of the intervention consisted of 2 components . ( 1 ) Pre- and postintervention completion of a self-administered survey assessed participants ' comfort in emergency situations and confidence to perform specific life-saving skills , using an ordinal scale : 1 = " strongly agree " to 5 = " strongly disagree " . ( 2 ) Practice s were contacted by telephone 12 months after the training to determine whether they had implemented improvements in emergency preparedness , including instituting mock codes , preparing a written emergency protocol and purchasing new emergency equipment and medications . Results : Eleven group pediatric practice s participated , which were representative of urban , suburban , and rural offices in southwestern Pennsylvania . Ninety-seven of a total 164 ( 59 % ) physicians and staff members completed both pre- and postintervention surveys . Practitioner participants were analyzed in 2 groups . Group 1 consisted of physicians , nurse practitioners , and physician assistants ; group 2 consisted of registered nurses , licensed practical nurses , and medical assistants . Comparison of pre- versus postintervention surveys in both of these groups revealed significant improvement in reported confidence to perform resuscitation skills that were included in the mock code after the training : airway positioning ( group 1 , 67 % vs. 94 % , P < 0.001 ; group 2 , 55 % vs. 75 % , P = 0.003 ) , airway suctioning , ( group 1 , 64 % vs. 88 % , P = 0.005 ; group 2 , 27 % vs. 51 % , P < 0.001 ) , and bag-mask assisted ventilation ( group 1 , 82 % vs. 91 % , P = 0.003 ; group 2 , 39 % vs. 71 % , P < 0.001 ) . In addition , group 1 reported more confidence in their ability to place an intraossesous line ( 24 % vs. 39 % , P = 0.003 ) and group 2 showed a significant increase in their confidence to administer oxygen ( 65 % vs. 84 % , P < 0.001 ) . As a result of the mock code , 83 % of all participants , both medical and nonmedical staffs , and 96 % of physicians felt less anxious about medical emergencies in the office . Twelve months after the conclusion of the program , 18 % of offices had conducted 1 or more mock codes , 64 % of offices had written an emergency protocol , and 27 % of offices had acquired essential resuscitation medications or equipment . Conclusions : The results of this study support the recommendation that mock codes should be performed in the pediatric primary care setting to improve practitioner confidence and decrease practitioner anxiety Background Benefits of skills lab training are widely accepted , but there is sparse research on its long-term effectiveness . We therefore conducted a prospect i ve , r and omised controlled-trial to investigate whether in a simulated setting students trained according to a " best practice " model ( BPSL ) perform two skills of different complexity ( nasogastral tube insertion , NGT ; intravenous cannulation , IVC ) better than students trained with a traditional " see one , do one " teaching approach ( TRAD ) , at follow-up of 3 or 6 months . Methodology and Principal Findings 94 first-year medical students were r and omly assigned to one of four groups : BPSL training or TRAD teaching with follow-up at 3 ( 3 M ) or 6 ( 6 M ) months . BPSL included structured feedback , practice on manikins , and Peyton ’s " Four-Step-Approach " , while TRAD was only based on the " see one - do one " principle . At follow-up , manikins were used to assess students ’ performance by two independent blinded video-assessors using binary checklists and a single-item global assessment scale . BPSL students scored significantly higher immediately after training ( NGT : BPSL3 M 94.8%±0.2 and BPSL6 M 95.4%±0.3 percentage of maximal score ± SEM ; TRAD3 M 86.1%±0.5 and TRAD6 M 84.7%±0.4 . IVC : BPSL3 M 86.4%±0.5 and BPSL6 M 88.0%±0.5 ; TRAD3 M 73.2%±0.7 and TRAD6 M 72.5%±0.7 ) and lost significantly less of their performance ability at each follow-up ( NGT : BPSL3 M 86.3%±0.3 and TRAD3 M 70.3%±0.6 ; BPSL6 M 89.0%±0.3 and TRAD6 M 65.4%±0.6 ; IVC : BPSL3 M 79.5%±0.5 and TRAD3 M 56.5%±0.5 ; BPSL6 M 73.2%±0.4 and TRAD6 M 51.5%±0.8 ) . In addition , BPSL students were more often rated clinical ly competent at all assessment times . The superiority at assessment after training was higher for the more complex skill ( IVC ) , whereas NGT with its lower complexity profited more with regard to long-term retention . Conclusions This study shows that within a simulated setting BPSL is significantly more effective than TRAD for skills of different complexity assessed immediately after training and at follow-up . The advantages of BPSL training are seen especially in long-term retention BACKGROUND AND OBJECTIVE : Simulation-based medical education ( SBME ) is used to teach residents . However , few studies have evaluated its clinical impact . The goal of this study was to evaluate the impact of an SBME session on pediatric interns ’ clinical procedural success . METHODS : This r and omized trial was conducted at 10 academic medical centers . Interns were surveyed on infant lumbar puncture ( ILP ) and child intravenous line placement ( CIV ) knowledge and watched audiovisual expert modeling of both procedures . Participants were r and omized to SBME mastery learning for ILP or CIV and for 6 succeeding months reported clinical performance for both procedures . ILP success was defined as obtaining a sample on the first attempt with < 1000 red blood cells per high-power field or fluid described as clear . CIV success was defined as placement of a functioning catheter on the first try . Each group served as the control group for the procedure for which they did not receive the intervention . RESULTS : Two-hundred interns participated ( 104 in the ILP group and 96 in the CIV group ) . Together , they reported 409 procedures . ILP success rates were 34 % ( 31 of 91 ) for interns who received ILP mastery learning and 34 % ( 25 of 73 ) for controls ( difference : 0.2 % [ 95 % confidence interval : –0.1 to 0.1 ] ) . The CIV success rate was 54 % ( 62 of 115 ) for interns who received CIV mastery learning compared with 50 % ( 58 of 115 ) for controls ( difference : 3 % [ 95 % confidence interval : –10 to 17 ] ) . CONCLUSIONS : Participation in a single SBME mastery learning session was insufficient to affect pediatric interns ’ subsequent procedural success OBJECTIVE To evaluate the effectiveness of an educational intervention on pediatric residents ' resuscitation fund of knowledge , technical skills , confidence , and overall performance . DESIGN Prospect i ve , nonconcurrent , controlled interventional trial . SETTING Urban pediatric tertiary care hospital . PARTICIPANTS An intervention group ( IG ) of 28 pediatric residents graduating in 1997 , and a control group ( CG ) of 30 pediatric residents graduating in 1996 . INTERVENTIONS Resuscitation course with didactic lectures and skills practice stations , as well as a minimum of 3 practice mock resuscitations with immediate feedback throughout postgraduate year 3 . MAIN OUTCOME MEASURES Fund of knowledge , using the Pediatric Advanced Life Support test and short answer test ; technical skills , using the Airway and Vascular Access Skills Assessment ; experience and confidence , using an anonymous survey ; and overall performance , evaluated using a videotaped mock resuscitation test . RESULTS The IG scored better on the short answer test ( P<.001 ) . A larger number of IG residents were successful in the completion of ancillary airway maneuvers and femoral vascular access ( P = .02 ) , as well as endotracheal intubation ( P = .004 ) and intraosseous access ( P = .002 ) . The IG was more confident in their leadership role ( P = .0001 ) and technical skills ( P = .05 ) . Trends toward improved overall performance were noted for the IG mock resuscitations . Residents in the IG were more likely to assess the airway in fewer than 2 minutes ( P = .02 ) , recognize the threat to life in fewer than 5 minutes ( P = .02 ) , and complete the primary survey in a timely fashion ( P = .05 ) . They required fewer prompts ( P = .04 ) and made fewer mistakes ( P = .07 ) . CONCLUSIONS A structured , formal curriculum can improve the necessary fund of knowledge , skills , confidence , and leadership required for resuscitation Background Unsuccessful or traumatic lumbar punctures ( LPs ) occur commonly and contribute to patient discomfort and to challenges in medical decision making in the pediatric emergency department ( ED ) . Objective We produced an instructional video demonstrating the best practice s in pediatric LP technique . We hypothesized that the performance of LPs would change and the rate of successful LPs would increase after watching the video . Methods This was a prospect i ve study of LPs performed in an urban , academic pediatric ED before and after an educational intervention . Lumbar punctures performed during year 1 constituted the control arm . During year 2 , all medical practitioners working in the ED watched the instructional video , and this constituted the interventional arm . The practitioner performing the LP completed a st and ardized data collection form after each LP procedure , and medical records were review ed . Results Data forms were collected on 668 LPs during the study period , 391 during year 1 and 277 during year 2 . There was neither a significant change in overall LP success rate between the 2 years ( 56.8 % year 1 vs 53.4 % year 2 ) nor a significant difference in median number of LP attempts required per patient ( P = 0.78 ) . Seventy-eight percent of participants who viewed the LP video during year 2 stated that the video helped increase their comfort level with performing LPs . The odds of using the techniques endorsed in the educational video were significantly higher during year 2 compared to year 1 for use of local anesthetic , early stylet removal , and vertical patient position . Conclusions The video increased practitioners ’ comfort level with the performance of pediatric LPs and adherence to evidence -based best practice s. It was not associated with an increased rate of successful LPs BACKGROUND We studied the reasons why patients undergoing thoracenteses performed in our outpatient pulmonary clinic had a higher frequency of iatrogenic pneumothorax compared to that in the concurrent radiology practice in our institution , which utilizes ultrasound guidance . We review ed our practice model and implemented a unique experiential training paradigm in a zero-risk simulation environment to improve efficacy , timeliness , service orientation , and safety . METHODS We retrospectively determined the rate of clinical ly significant pneumothoraces in our practice ( phase I , July 1 , 2001 , to June 30 , 2002 ) . The training system re design included the following : ( 1 ) a design ated group of pulmonologist instructors dedicated to treating pleural disease and reducing the number of iatrogenic complications ; ( 2 ) the use of ultrasound image guidance for all thoracenteses ; and ( 3 ) structured proficiency and competency st and ards for proceduralists . Postintervention ( phase II ) data were prospect ively collected ( January 2005 to December 2006 ) and compared with our baseline data . RESULTS The baseline rate of pneumothorax was 8.6 % ( 5 of 58 patients ) in our pulmonary practice . Following intervention ( phase II ) , the rate of pneumothorax declined to 1.1 % ( p = 0.0034 ) . During phase II , the number of thoracenteses performed increased ( 186 vs 58 per year , respectively ; p < 0.05 ) . The iatrogenic pneumothorax rate was stable in the 2 years following intervention ( 2005 , 0.7 % [ 1 of 137 pneumothoraces ] ; 2006 , Output:	Evidence is strongest for the use of simulation and competency-based paradigms in teaching procedures , and these approaches should be the mainstay of programmes that train physicians to perform procedures .
MS21631	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE This study examined the effectiveness of three peer-facilitated brief alcohol interventions -small group motivational interviewing , motivationally enhanced peer theater , and an interactive alcohol-education program-with students engaging in high-risk drinking who were referred for alcohol policy violations . METHOD Undergraduate students referred for alcohol policy violations ( N = 695 ) at a large northeastern public university were r and omized to one of the three conditions . Six-month follow-up data were collected on drinking frequency and quantity , negative consequences , use of protective behaviors , and perceptions of peers ' drinking norms . RESULTS There were no statistically significant overall pre-post effects or treatment effects . However , exploratory analyses indicated that decreases in perceived norms and increases in use of protective behavioral strategies were associated with reductions in alcohol use and alcohol-related problems at follow-up ( p < .01 ) . CONCLUSIONS The presence of nonsignificant pre-post or main effects is , in part , consistent with recent research indicating that sanctioned college students may immediately reduce drinking in response to citation and that brief interventions may not contribute to additional behavioral change . The presence of statistically significant correlations between alcohol use and related problems with corrections in norms misperceptions and increased use of protective behaviors at the individual level holds promise for both research and practice . The integration of elements addressing social norms and use of protective behaviors within brief cognitive-behavioral intervention protocol s delivered by trained peer facilitators warrants further study using r and omized clinical trials AIM To establish the efficacy of a brief motivational intervention compared to feedback only when delivered in an emergency department for reducing alcohol use and problems among young adults . DESIGN Two-group r and omized controlled trial with follow-up assessment s at 6 and 12 months . SETTING Level I Trauma Center . PARTICIPANTS A total of 198 18 - 24-year-old patients who were either alcohol positive upon hospital admission or met screening criteria for alcohol problems . INTERVENTION Participants were assigned r and omly to receive a one-session motivational intervention ( MI ) that included personalized feedback , or the personalized feedback report only ( FO ) . All participants received additional telephone contact 1 month and 3 months after baseline . MEASUREMENTS Demographic information , alcohol use , alcohol problems and treatment seeking . FINDINGS Six months after the intervention MI participants drank on fewer days , had fewer heavy drinking days and drank fewer drinks per week in the past month than did FO patients . These effects were maintained at 12 months . Clinical significance evaluation indicated that twice as many MI participants as FO participants reliably reduced their volume of alcohol consumption from baseline to 12 months . Reductions in alcohol-related injuries and moving violations , and increases in alcohol treatment-seeking were observed across both conditions at both follow-ups with no differences between conditions . CONCLUSIONS This study provides new data supporting the potential of the motivational intervention tested to reduce alcohol consumption among high-risk youth AIMS This study aim ed at testing the effectiveness of a brief motivational intervention ( BI ) compared with a minimal intervention ( MI ) for reducing alcohol consumption in adult , alcohol-positive traffic casualties . METHODS Patients were recruited at the emergency room of a trauma hospital and screened for alcohol by a qualitative saliva test ( positive from a blood alcohol concentration of 0.02 g/l ) . Positive patients ( 13.3 % ) who accepted entering the study were r and omly allocated into BI and MI . Baseline assessment was the same for all patients . Blind telephone follow-ups were performed at months 3 , 6 , and 12 , and results were analysed by protocol and by intention-to-treat analysis . RESULTS After 1 year of follow-up , 67 % of the patients had reduced their consumption , the percentage of heavy drinkers had dropped by 47 % , and 62 % of baseline AUDIT-C positive patients ( hazardous drinkers ) had become negative . Binge drinking dropped significantly ( P < 0.05 ) . Results at month 12 were in line with the previous ones . CONCLUSIONS The effectiveness of BI compared with MI has not been verified , but a significant reduction in consumption has been observed in the whole sample , without significant differences by type of intervention . The persistence and dimension of changes suggest a real effect of both interventions , although the lack of a pure control group does not allow definitive conclusions . Traffic casualties are in a teachable moments to benefit from easy and cheap interventions This study tested the efficacy of behavioral treatments for alcohol use disorders ( AUD ) among men who have sex with men ( MSM ) and who are at risk for HIV transmission . HIV-negative MSM with current AUD ( N = 198 ) were recruited , offered treatment focused on reducing drinking and HIV risk , and followed during treatment and 12 months posttreatment . Participants ( n = 89 ) accepted treatment and were r and omized to either 4 sessions of motivational interviewing ( MI ) or 12 sessions of combined MI and coping skills training ( MI + CBT ) . Other participants ( n = 109 ) declined treatment but were followed , forming a non-help-seeking group ( NHS ) . MI yielded significantly better drinking outcomes during the 12-week treatment period than MI + CBT , but posttreatment outcomes were equivalent . NHS participants significantly reduced their drinking as well . Service delivery and treatment research implication s are discussed OBJECTIVES Adolescents in their late teens and early 20s have the highest alcohol consumption in the United States ; binge drinking peaks at age 21 - 25 years . Underage drinking is associated with many negative consequences , including academic problems and risk of intentional and unintentional injuries . This study tested the effectiveness of pediatric emergency department ( PED ) screening and brief intervention to reduce alcohol consumption and associated risks . METHODS A three-group r and omized assignment trial was structured to test differences between intervention ( I ) and st and ard assessed control ( AC ) groups in alcohol consumption and alcohol-related behaviors from baseline to 12 months and to compare the AC group with a minimally assessed control ( MAC ) group to adjust for the effect of assessment reactivity on control group behavior . Patients aged 14 - 21 years were eligible if they screened positive on the Alcohol Use Disorders Identification Test ( AUDIT ) or for binge drinking or high-risk behaviors . The MAC group received a re source h and out , written advice about alcohol-related risks , and a 12-month follow-up appointment . Patients in the AC group were assessed using st and ardized instruments in addition to the MAC protocol . The I group received a peer-conducted motivational intervention , referral to community re sources and treatment if indicated , and a 10-day booster in addition to assessment . Measurements included 30-day self-report of alcohol consumption and alcohol-related behaviors , screens for depression and posttraumatic stress disorder , and self-report of attempts to quit , cut back , or change conditions of use , all repeated at follow-up . Motor vehicle records and medical records were also analyzed for changes from baseline to 1-year follow-up . RESULTS Among 7,807 PED patients screened , 1,202 were eligible ; 853 enrolled ( I , n = 283 ; AC , n = 284 ; MAC , n = 286 ) , with a 12-month follow-up rate of 72 % . At 12 months , more than half of enrollees in Reaching Adolescents for Prevention ( RAP ) attempted to cut back on drinking , and over a third tried to quit . A significantly larger proportion of the I group made efforts to quit drinking and to be careful about situations when drinking compared to AC enrollees , and there was a numerically but not significantly greater likelihood ( p = 0.065 ) among the I group for efforts to cut back on drinking . At 3 months , the likelihood of the I group making attempts to cut back was almost triple that of ACs . For efforts to quit , it was double , and for trying to be careful about situations when drinking , there was a 72 % increase in the odds ratio ( OR ) for the I group . Three-month results for attempts were sustained at 12 months for quit attempts and efforts to be careful . Consumption declined in both groups from baseline to 3 months to 12 months , but there were no significant between-group differences in alcohol-related consequences at 12 months or in alcohol-related risk behaviors . We found a pattern suggestive of assessment reactivity in only one variable at 12 months : the attempt to cut back ( 73.3 % for the I group vs. 64.9 % among the AC group and 54.8 % among the MAC group ) . CONCLUSIONS Brief motivational intervention result ed in significant efforts to change behavior ( quit drinking and be careful about situations while drinking ) but did not alter between-group consumption or consequences By the age of 18 , between 16 and 27 % of adolescents in the U.S. have been arrested for an offense and by the age of 23 this increases to a staggering 25 - 41 % . Most youth that get into legal trouble have a substance abuse problem and many youth report high risk driving behaviors . Adjudication of adolescents for an offense may provide an opportunity to provide a secondary prevention program for such high risk behaviors . In this regard the primary aim of the present study was to test two hypotheses : ( 1 ) that interventions involving group motivational interviewing would decrease future legal charges beyond those achieved by the combination of sanctions and remedial actions otherwise m and ated by the court ; and ( 2 ) that the addition of a trauma room exposure to the group MI intervention would increase the effectiveness of MI in decreasing these future legal charges . Court m and ated youth who have had a high risk driving police charge and /or alcohol related police charge and who are drivers ( n=992 ) were r and omly assigned to one of the three 20h interventions ; enhanced prototypic community service ( CS ) , Motivational Intervention with typical community service ( MI ) , and Motivational Intervention with exposure to a hospital trauma center ( MI-H ) . As hypothesized , the probability of being charged with an offense within the 6 months post-treatment was significantly less for participants in the combined MI groups than those in the CS group . The combined MI groups also had significantly fewer overall number of police charge events than the CS group at 6 months . Mediation analyses revealed that the relationship between MI vs. CS interventions and subsequent police charges was partially accounted for by the youth 's experience of the MI component of the intervention . Despite fewer police charges at 6 months the combined MI group reported ( 1 ) significantly more hazardous drinking and ( 2 ) a greater amount of speeding and distracted driving than the control group over this same 6-month period . Hypothesis 2 , that MI-H would be more effective than MI in reducing police charges , was not supported . This was so despite evidence supporting the hypotheses that ( 1 ) trauma room exposure would increase participants ' emotional arousal during the intervention and ( 2 ) increased arousal would be predictive of fewer police charges . Despite support for the theorized causal pathway , the combination of trauma room exposure and MI did not result in better outcomes than MI combined with traditional community service . Given this discrepancy between empirical supports for the theory in the face of the absence of incremental effectiveness of the MI-H treatment condition , a better underst and ing of the participant 's hospital experience will be necessary if we are to successfully utilize the trauma room exposure to increase the effectiveness of MI interventions for this target group to achieve better outcomes OBJECTIVE To determine whether a brief individual motivational interview ( IMI ) plus a family motivational interview ( Family Check-Up [ FCU ] ) would reduce alcohol use in adolescents treated in an emergency department after an alcohol-related event more effectively than would an IMI only . DESIGN Two-group r and omized design with 3 follow-up time points . SETTING An urban regional level I trauma center . PARTICIPANTS Adolescents aged 13 to 17 years ( N = 125 ) with a positive blood alcohol concentration as tested using blood , breath , or saliva . INTERVENTIONS Either IMI or IMI plus FCU . MAIN OUTCOME MEASURES Drinking frequency ( days per month ) , quantity ( drinks per occasion ) , and frequency of high-volume drinking ( ≥5 drinks per occasion ) . RESULTS Both conditions result ed in a reduction in all drinking outcomes at all follow-up points ( P < .001 for all ) , with the strongest effects at 3 and 6 months . Adding the FCU to the IMI result ed in a somewhat better outcome than did the IMI only on high-volume drinking days at 3-month follow-up ( 14.6 % vs 32.1 % , P = .048 ; odds ratio , 2.76 ; 95 % confidence interval , 0.99 - 7.75 ) . CONCLUSIONS Motivational interventions have a positive effect on drinking outcomes in the short term after an alcohol-related emergency department visit . Adding the FCU to an IMI result ed in somewhat better effects on high-volume drinking at short-term follow-up than did an IMI only . The cost of extra sessions necessary to complete the FCU should be weighed against the potential benefit of reducing high-volume drinking when considering adding the FCU to an IMI for this population OBJECTIVE Motivational interviewing to reduce alcohol and marijuana use among incarcerated adolescents was evaluated . METHOD Adolescents ( N = 162 , 84 % male ; M = 17.10 years old ) were r and omly assigned to receive motivational interviewing or relaxation training , with follow-up assessment 3 months after release . RESULTS Compared with those who received relaxation training , adolescents who received motivational interviewing had lower rates of alcohol and marijuana use at follow-up , with some evidence for moderating effects of depression . At low levels of depression , adolescents who received motivational interviewing had lower rates of use . Adoles Output:	We also considered other outcomes and at four or more months follow-up we found no effects on drink-driving ( SMD -0.11 ; 95 % CI -0.31 to 0.09 ) , moderate quality of evidence ; or other alcohol-related risky behaviour ( SMD -0.14 ; 95 % CI -0.30 to 0.02 ) , moderate quality of evidence .Further analyses showed that the type of control comparison ( assessment only versus alternative intervention ) did not predict the outcome in a clear or straightforward way ; and there was no consistent relationship between the duration of the MI intervention ( in minutes ) and effect size . The results of this review indicate that there are no substantive , meaningful benefits of MI interventions for the prevention of alcohol misuse .
MS21632	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES This is a controlled , prospect i ve study which compares the effects of a low-dose heat patch for self-medication on the reduction of pain symptoms in dysmenorrhea . METHODS The sample group included female sophomore students study ing at a university in Istanbul , Turkey , between 2007 and 2008 . These female participants completed the Dysmenorrhea Identification Form to determine the sample group , and a total of 193 female students possessed the eligible criteria . The research control group consisted of 66 patients , the analgesia group consisted of 61 , and the heat patch group consisted of 66 . The control group did not use any treatments , while the self-medication group used analgesic medication ( single dose ) , and the heat patch group applied a heat patch on the lower abdomen , against the skin , for an application period of 2 menstrual cycles . Using a visual analog scale ( VAS ) , the pain severity was recorded at the baseline , after 4 hours of intervention , and after 8 hours of intervention . The data were examined using ANOVA . RESULTS There were significant differences between the groups in terms of pain severity after 8 hours of application ( P < .001 ) . All groups had similar pain levels at baseline and during the fourth and eighth hours , with no significant differences between the groups during the first and the second menstrual cycles ( P > .05 ) . CONCLUSION The authors conclude that the heat patch is an effective method for reducing dysmenorrhea OBJECTIVES The aim of this study was to evaluate the effects of auricular acupressure on relieving menstrual symptoms and decreasing nitric oxide ( NO ) for women with primary dysmenorrhea . DESIGN This was a r and omized clinical trial comparing the effects of auricular acupressure by seed-pressure method and placebo adhesive patch . SETTING Setting s included colleges in northern and central Taiwan . SUBJECTS Serum CA-125 testing was used as a screening test for primary dysmenorrhea ( < 35 mg/dL ) . The study included 36 college females r and omized to acupressure group , 35 to control group . INTERVENTIONS The acupressure group received auricular acupressure by seed-pressure method on liver ( CO12 ) , kidney ( CO10 ) , and endocrine ( CO18 ) acupoints . The control group had a plain adhesive patch placed on the same acupoints with no seed attached . Acupressure protocol included massaging 15 times on each acupoint , 3 times a day , for a total of 20 days . OUTCOME MEASURES Primary : Short-form Menstrual Distress Question naire ( MDQs ) . Secondary : blood sample of NO . Assessment s of MDQs and NO were performed at baseline and within the first 2 days of their next menses ( after completion of 20 days of acupressure ) . RESULTS In the acupressure group , the overall menstrual symptoms ( 95 % confidence interval [ CI ] = -49.8 to -6.5 , effect size [ ES ] = 0.43 , p = 0.01 ) and two subscales , menstrual pain ( 95 % CI = -16.4 -to -2.2 , ES = 0.45 , p = 0.01 ) and negative affects ( 95 % CI = -11.9 - 2.0 , ES = 0.38 , p = 0.04 ) , revealed that menstrual symptoms decreased significantly after auricular acupressure by the seed-pressure method . The ES for the MDQs were in favor of the auricular acupressure by seed-pressure method . NO level increased in the acupressure group , although this difference did not achieve statistical significance ( p > 0.05 ) . CONCLUSIONS This study supports the effects of auricular acupressure by seed-pressure method in improving menstrual symptoms , and offers a noninvasive complementary therapy for women with primary dysmenorrhea OBJECTIVE We have evaluated the clinical efficacy of yoga for primary dysmenorrhea . Primary dysmenorrhea occurs in 50 % of female adolescents and is a common problem in women of reproductive age . We have assessed whether three yoga poses ( Cobra , Cat , and Fish Poses ) are able to reduce severity and duration of primary dysmenorrhea . METHODS To determine the effectiveness of yoga in adolescents with primary dysmenorrhea , 92 girl students,18 - 22 years old , were r and omly assigned to an experimental group ( n = 50 ) and a control group ( n = 42 ) . The Visual Analog Scale for Pain was used to assess intensity of pain and the pain duration was calculated in terms of hours . Each group was evaluated for three menstrual cycles . At first cycle no method was presented ; the participants only were asked to complete the question naire of menstrual characteristics during their menstrual . Then the participants were asked by the experimental group to do yoga poses at luteal phase , and also to complete the menstrual characteristics question naire in during of menstruation . The control group did not receive any intervention except to complete menstrual characteristics question naire in during of menstruation . RESULTS There was a significant difference in the pain intensity and pain duration in the post-tests compared with the pretest in yoga group ( P < 0.05 ) . The results showed that compared with the Control group , there was a significant difference in the pain intensity and pain duration in the experimental group ( P < 0.05 ) . CONCLUSION Yoga reduced the severity and duration of primary dysmenorrhea . The findings suggest that yoga poses are safe and simple treatment for primary dysmenorrhea BACKGROUND : There are two types of primary dysmenorrhea ( spasmodic and congestive ) which differ from each other in terms of the occurrence time in menstrual cycle , pain quality and other symptoms . The present study aim ed to determine the effect of acupressure at the Sanyinjiao point ( SP-6 ) on severity of menstrual symptoms ( primary outcome ) and the duration of resting time as well as the number of ibuprofen consumption ( secondary outcome ) in the two types of primary dysmenorrhea . METHODS : This was a clustered r and omized controlled trial on 72 eligible students residing in dormitories of public universities of Tabriz , Iran . Determining the type of primary dysmenorrhea using a Menstrual symptoms question naire ( MSQ ) , 36 participants which suffered from each type of dysmenorrhea were enrolled from the four dormitories . The dormitories were r and omly divided into intervention and control groups . No intervention was carried out at the first cycle . During the two next cycles , Sanyinjiao point of the subjects in the intervention group was pressed for twenty minutes at the time of pain . The subjects in both groups were allowed to consume ibuprofen , if needed . During these three cycles , the participants recorded and reported menstrual symptoms severity , duration of resting time and the number of the used ibuprofen . RESULTS : The severity of menstrual symptoms and duration of resting time in the 2nd and 3rd cycles were significantly reduced more than control groups for both spasmodic and congestive types of primary dysmenorrhea . In addition , the aver-age numbers of ibuprofen pills taken by both intervention groups was significantly less than the control groups . There was no significant difference between the two intervention groups in terms of any of the outcomes . CONCLUSIONS : Acupressure is effective on lowering the symptoms of dysmenorrhea and duration of resting time almost equally in both spasmodic and congestive types . Therefore , using this method either alone or along with other methods is recommended to treat dysmenorrhea OBJECTIVES Dysmenorrhea is a common gynecologic disorder . Although non-steroidal anti-inflammatory drugs are commonly used , due to their side effects and lack of response in some individuals , other approaches such as exercise have been considered . This study compared the effect of stretching exercises and mefenamic acid on the reduction of pain and menstruation characteristics in primary dysmenorrhea . METHODS In this r and omized clinical trial , 122 female students with moderate to severe dysmenorrhea were assessed and were placed in either the exercise or mefenamic acid group . The exercise program was performed for 15 minutes , three times a week and included a five-minute warm up and six belly and pelvic stretching exercises for 10 minutes . The mefenamic acid group received 250 mg capsules every eight hours from the onset of menstruation until pain relief . Both interventions were performed during two consecutive menstrual cycles . Pain intensity was measured using a 10 cm visual analog scale . RESULTS The mean pain intensity was significantly higher in the exercise group only in the first cycle ( p = 0.058 ) . In the second cycle , the mean difference in pain reduction in the exercise group was higher than the mefenamic group compared to the start of the study ( p = 0.056 ) and the first cycle ( p = 0.007 ) . There was no significant difference in the severity and duration of pain between the groups ( p > 0.050 ) . CONCLUSIONS Stretching exercises were as effective as mefenamic acid in the treatment of primary dysmenorrhea . Our results suggest that the effect of exercise on relieving menstruation pain increases over time The present study aims at comparing the effects of acupressure using new combination of acupoints , and Ibuprofen on the severity of primary dysmenorrhea ( PD ) . 216 female high school students , aged between 14 to 18 years , were r and omly selected and divided into three groups . Each group underwent different treatment techniques : acupressure , Ibuprofen and sham acupressure as a placebo . The results indicated that the three therapeutic techniques were significantly effective in reducing the pain . However the therapeutic efficacies of acupressure and Ibuprofen were similar with no significant difference , and were significantly better than the placebo . Thus acupressure , with no complications , is recommended as an alternative and also a better choice in the decrease of the severity of PD Background Primary dysmenorrhea is a common and sometimes disabling condition . In recent years , some studies aim ed to improve the treatment of dysmenorrhea , and therefore , introduced several therapeutic measures . This study was design ed to compare the analgesic effect of iron chip containing heat wrap with ibuprofen for the treatment of primary dysmenorrhea . Methods In this r and omized ( I RCT 201107187038N2 ) controlled trial , 147 students ( 18–30 years old ) with the diagnosis of primary dysmenorrhea were enrolled considering the CONSORT guideline . Screening for primary dysmenorrhea was done by a two- question screening tool . The participants were r and omly assigned into one of the intervention groups ( heat Patch and ibuprofen ) . Data regarding the severity and emotional impact of the pain were recorded by a shortened version of McGill Pain Question naire ( SF-MPQ ) . Student 's t test was used for statistical analysis . Results The maximum and minimum pain severities were observed at 2 and 24 hours in both groups . The severity of sensual pain at 8 , 12 , and 24 hours was non-significantly less in the heat Patch group . There was also no significant difference between the groups regarding the emotional impact of pain at the first 2 , 4 , 8 , 12 and 12 hours of menstruation . Conclusions Heat patch containing Iron chip has comparable analgesic effects to ibuprofen and can possibly be used for primary dysmenorrhea . Trial registration I RCT OBJECTIVE To determine if pain relief provided by a wearable heat wrap ( continuous , low-level , topical heat therapy ) is superior to oral acetaminophen for primary dysmenorrhea . STUDY DESIGN A r and omized , active-controlled , multisite , single-blind ( investigator ) , parallel- design study compared an abdominal wrap to an oral medication ( acetaminophen , 1000 mg ) over I day . Pain relief ( 0 - 5 ) and abdominal muscle tightness/cramping ( 0 - 100 ) were recorded at 12 time points . At 24 and 48 hours , menstrual symptom-based quality of life was assessed . RESULTS Three hundred sixty-seven subjects entered the study , with 344 subjects evaluable . The heat wrap was superior to acetaminophen for pain relief over an 8-hour period ( means of 2.48 and 2.17 , p = 0.015 ) and at t hours 3 , 4 , 5 and 6 ( p < or = 0.05 ) . Tightness/cramping was less for the heat wrap versus acetaminophen over 8 hours ( means of 40.4 and 44.5 , p = 0.04 ) and at hours 4 , 5 and 6 ( p < or = 0.05 ) . There was significantly decreased fatigue , fewer mood swings and less lower abdominal cramping ( p < or = 0.05 ) with heat therapy . CONCLUSION Continuous , low-level , topical heat therapy was superior to acetaminophen for the treatment of dysmenorrhea Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVES This study aims to evaluate the effects of Sanyinjiao ( SP6 ) acupressure in reducing the pain level and menstrual distress result ing from dysmenorrhea . METHODS Forty participants with dysmenorrhea were assigned to either the acupressure group ( n = 19 ) or the control group ( n = 21 ) . The acupressure group received 20 min of SP6 acupressure during the initial inter Output:	Conclusion Exercise showed large effects , while acupressure and heat showed moderate effects in reducing menstrual pain compared to no treatment . Both exercise and heat are potential alternatives to analgesic medication .
MS21633	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective : There have been a number of reports that natural foods such as garlic , honey , and capsaicin can inhibit Helicobacter pylori in vitro and each report has suggested the natural ingredient be used for treatment of the infection . We investigated whether garlic or capsaicin-containing peppers would actually inhibit H. pylori in vivo . Methods : We performed a prospect i ve crossover study in healthy H. pylori-infected adults . We used the urea breath test to assess the status of the H. pylori infection . On separate days subjects received three test meals consisting of beef , tortillas , and salad with one of the following : fresh garlic ( 10 sliced cloves ) , capsaicin ( six sliced fresh jalapeños ) , two tablets of bismuth subsalicylate ( Pepto-Bismol , positive control ) , or nothing added ( negative control ) . Breath testing was done before the first meal , the evening meal , and the following morning . At least 2 days elapsed between the test substances . Results : Twelve subjects participated ( seven men , five women ) , with an average age of 41.4 yr , range 27–51 yr . Ten subjects received garlic , six received jalapeños , and 11 received bismuth . Neither garlic nor capsaicin had any in vivo effect on H. pylori ( median urease activity 28.5 vs 39.8 and 43.7 vs 46.6 before and after garlic and jalapeños , respectively ) p > 0.8 . Bismuth had a marked inhibitory effect ( median 55.8 vs 14.3 before and after bismuth ) p < 0.001 , respectively . Conclusions : This study did not support a role for either garlic or jalapeños in the treatment of H. pylori infection . Caution must be used when attempting to extrapolate data from in vitro studies to the in vivo condition In this study , in vivo effectiveness of ascorbic acid ( AA ) , beta carotene ( BC ) and allicin in HP eradication were evaluated . 210 patients who are HP positive in biopsy were involved in this study . The patients r and omised to seven treatment groups ( each group consisting of 30 patients ) . The first group was given st and ard eradication treatment ( lansaprasol 30 mg bid , clarithromycin 500 mg bid , amoxicillin 1 g bid for 14 days ) . Second group received AA 1000 mg/day in addition to the st and ard treatment . Third group received only AA 1000 mg/day for 14 days . Fourth group was treated with st and ard regiment plus 120 mg/day BC . Fifth group was given only BC 120 mg/day for 14 days . Sixth group was given st and ard regiment and allicin 4200 micrograms/day . Seventh group received only Allicin 1200 micrograms/day for 14 days . The eradication was achieved in 20 ( 66.6 % ) in group I , 15 ( 50 % ) in group II , 3 ( 10 % ) in group III , 15 ( 50 % ) in group IV , 0 ( 0 % ) in group V , 27 ( 90 % ) in group VI and 7 ( 23.3 % ) in group VII . Allicin seemed to be potentially effective agent for HP eradication but ascorbic acid , beta caroten was found to be ineffective Resistance of Helicobacter pylori to clarithromycin and metronidazole is now found worldwide . Steam‐distilled garlic oil has in vitro activity against H. pylori and may be a useful alternative treatment strategy OBJECTIVE To characterize Helicobacter pylori isolates from western Argentina using virulence markers and antimicrobial susceptibility patterns in order to assess the association between virulent genotypes , antimicrobial resistance , and disease . DNA fingerprinting was also evaluated for the segregation of virulent or resistant strain clusters . METHODS Genotyping of 299 H. pylori isolates was performed by PCR using specific primers for the cagA , vacA and iceA genes . R and om amplification of polymorphic DNA (RAPD)-PCR and rep-PCR genetic clustering were assessed using five r and om primers and BOXA1R and ERIC primers , respectively . Resistance to clarithromycin ( Cla ) and metronidazole ( Mtz ) was assessed by the agar dilution method . RESULTS It was observed that 40.8 % of the genotypes were cagA-positive ; 66.9 % were vacA s1m1 genotype and the iceA1 allele was found in 40.8 % . A significant correlation ( p=0.0000 ) was observed between cagA positivity and vacA s1m1/iceA1 genotypes . Triple virulent genotypes were statistically associated with peptic ulcer ( PU ) ( p=0.0001 ) and Cla resistance ( p=0.0000 ) . RAPD fingerprints obtained with AO2 primers identified clusters that were strongly associated with PU , virulence markers , and resistance to Cla and Mtz . CONCLUSIONS The H. pylori isolates that harbored two or three virulence markers were more resistant to Cla and Mtz . Combined analysis of virulent genotypes and resistance patterns may permit identification of high-risk patients to prevent PU later in life or to avoid antimicrobial treatment failure Background : Due to increasing antimicrobial resistance , a bismuth-based quadruple regimen has been recommended as an alternative first-line therapy for Helicobacter pylori ( H pylori ) eradication . However , different results are varied greatly and the availability of bismuth was limited in some countries . We assessed the efficacy and safety of 14-day berberine-containing quadruple therapy as an alternative regimen for H pylori eradication . Methods : In a r and omized , open-label , non-inferiority , phase IV trial between November 25 , 2014 , and October 15 , 2015 , 612 treatment-naive patients were r and omly assigned to 14-day berberine-containing ( n = 308 ) or 14-day bismuth-containing ( n = 304 ) quadruple therapy . The primary outcomes were eradication rates determined by the 13C urea breath test ( 13C-UBT ) 28 days after the end of treatment . The secondary outcomes were adverse events and compliance . Results : The baseline demographic data including age , gender , body mass index ( BMI ) , general condition and severity score were not statistically different in both groups . The eradication rates in bismuth and berberine groups were 86.4 % ( 266/308 ) and 90.1 % ( 274/304 ) in intention-to-treat ( ITT ) analysis ( P = .149 ) , and 89.6 % ( 266/297 ) and 91.3 % ( 273/299 ) in per- protocol ( PP ) analysis ( P = .470 ) , respectively . No statistically significant difference was found in the overall incidence of adverse events between both groups ( 35.7 % vs 28.6 % , P = .060 ) . Conclusions : Both regimens achieved the recommended efficacy for H pylori eradication . The berberine-containing quadruple regimen was not inferior to bismuth-containing quadruple regimen and can be recommended as an alternative regimen for H pylori eradication in the local region Purpose The present study was done to assess the prevalence rate , antibiotic resistance pattern and genotyping status of the Helicobacter pylori strains isolated from human and animal gastric biopsy sample s. Patients and methods A total of 1,150 gastric biopsy sample s were r and omly collected from humans ( children and adults ) and animals ( cows , sheep and goats ) . All sample s were subjected to culture , urease test and histopathologic examination . H. pylori isolates were also confirmed using the 16S rRNA gene PCR-amplification . Antibiotic resistance pattern was assessed by the disk diffusion method . Distribution of different genotypes was studied by PCR . Results The prevalence of H. pylori in gastric biopsy sample s which were studied using urease test , culture and histological examination were 57.04 % , 55.40 % and 60.80 % , respectively . Sample s that were collected from adult humans ( 78 % ) and sheep ( 70 % ) had the highest prevalence of H. pylori strains , while those of goats ( 0.6 % ) and cows ( 4 % ) had the lowest . Findings of the culture method were confirmed using PCR-based amplification of 16S rRNA . Distribution of H. pylori among the gastric ulcers , duodenal ulcers , chronic gastritis gastric cancer and chronic cancer sample s were 10.40 % , 15.70 % , 96.50 % , 0.60 % and 3.14 % , respectively . H. pylori strains harbored the highest prevalence of resistance against ampicillin ( 74.4 % ) , clarithromycin ( 63.4 % ) , trimethoprim ( 61.5 % ) and metronidazole ( 61.5 % ) . The most commonly detected genotypes among the H. pylori strains isolated from different types of biopsy sample s were cagA ( 84.79 % ) , vacA m2 ( 55.95 % ) , vacA s1a ( 49.84 % ) , cagE ( 48.58 % ) , iceA1 ( 47.02 % ) and iceA2 ( 47.02 % ) . Conclusion High prevalence of antibiotic resistance and virulent genotypes indicates an important public health issue . Similarities in antibiotic resistance and genotyping pattern of H. pylori strains isolated from humans and animals may show their similar routes of infection Output:	CONCLUSION Allicin as an add-on therapy improves H. pylori eradication , healing of ulcers , and remission of symptoms .
MS21634	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: CONTEXT Laboratory findings have suggested that oxidative stress may contribute to the pathogenesis of Alzheimer disease . Therefore , the risk of Alzheimer disease might be reduced by intake of antioxidants that counteract the detrimental effects of oxidative stress . OBJECTIVE To determine whether dietary intake of antioxidants is related to risk of Alzheimer disease . DESIGN AND SETTING The Rotterdam Study , a population -based , prospect i ve cohort study conducted in the Netherl and s. PARTICIPANTS A total of 5395 participants who , at baseline ( 1990 - 1993 ) , were aged at least 55 years , free of dementia , and noninstitutionalized and had reliable dietary assessment . Participants were reexamined in 1993 - 1994 and 1997 - 1999 and were continuously monitored for incident dementia . MAIN OUTCOME MEASURES Incidence of Alzheimer disease , based on Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition ( DSM-III-R ) criteria and National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer Disease and Related Disorders Association ( NINCDS-ADRDA ) criteria , associated with dietary intake of beta carotene , flavonoids , vitamin C , and vitamin E. RESULTS After a mean follow-up of 6 years , 197 participants developed dementia , of whom 146 had Alzheimer disease . When adjustments were made for age , sex , baseline Mini-Mental State Examination score , alcohol intake , education , smoking habits , pack-years of smoking , body mass index , total energy intake , presence of carotid plaques , and use of antioxidative supplements , high intake of vitamin C and vitamin E was associated with lower risk of Alzheimer disease ( rate ratios [ RRs ] per 1-SD increase in intake were 0.82 [ 95 % confidence interval [ CI ] , 0.68 - 0.99 ] and 0.82 [ 95 % CI , 0.66 - 1.00 ] , respectively ) . Among current smokers , this relationship was most pronounced ( RRs , 0.65 [ 95 % CI , 0.37 - 1.14 ] and 0.58 [ 95 % CI , 0.30 - 1.12 ] , respectively ) and also was present for intake of beta carotene ( RR , 0.49 [ 95 % CI , 0.27 - 0.92 ] ) and flavonoids ( RR , 0.54 [ 95 % CI , 0.31 - 0.96 ] ) . The associations did not vary by education or apolipoprotein E genotype . CONCLUSION High dietary intake of vitamin C and vitamin E may lower the risk of Alzheimer disease Abstract The traditional Mediterranean diet ( MedDiet ) has shown beneficial effects on cognitive decline . Nevertheless , diet – gene interactions have been poorly evaluated . We aim ed to investigate diet – gene interaction in the PREDIMED-NAVARRA r and omized trial . A total of 522 participants ( 67 ± 6 years at baseline ) enrolled in the PREDIMED-NAVARRA trial were r and omly allocated to one of three diets : two MedDiets ( supplemented with either extra-virgin olive oil or nuts ) or a low-fat diet . They were evaluated with the Mini-Mental State Examination ( MMSE ) and the Clock Drawing Test ( CDT ) after 6.5 years of intervention . Subjects were genotyped for CR1-rs3818361 , CLU-rs11136000 , PICALM-rs3851179 and Apolipoprotein E ( ApoE ) genes . We studied MedDiet – gene interactions for cognition and assessed the effect of the MedDiet on cognition across different genetic profiles . A significant interaction ( p = 0.041 ) between CLU-rs11136000 and the MedDiet intervention on the MMSE was found with a beneficial effect of MedDiet among carriers of the T minor allele ( B = 0.97 , 95 % CI 0.45–1.49 ) . Similar effect was observed for CR1-rs3818361 , but no significant interaction was observed ( p = 0.335 ) . For PICALM-rs3851179 , the MedDiet intervention showed a beneficial effect in both genotype groups . No apparent interaction was found for the CDT between intervention and gene variants . Similarly , participants r and omly allocated to MedDiet groups , with favorable profiles of CR1 , CLU and PICALM genes , significantly improved CDT scores compared to controls with the same genetic profile . Cognitive performance was better for non-ApoE4 and for ApoE4 carriers of MedDiet groups compared to controls , but for CDT performance , we only found statistical significant differences for non-ApoE4 carriers . A MedDiet intervention modulates the effect of genetic factors on cognition . The effect of MedDiet might be greater for subjects with a more favorable genetic profile BACKGROUND Adherence to a Mediterranean diet may improve longevity , but relevant data are limited . METHODS We conducted a population -based , prospect i ve investigation involving 22,043 adults in Greece who completed an extensive , vali date d , food-frequency question naire at base line . Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean-diet scale that incorporated the salient characteristics of this diet ( range of scores , 0 to 9 , with higher scores indicating greater adherence ) . We used proportional-hazards regression to assess the relation between adherence to the Mediterranean diet and total mortality , as well as mortality due to coronary heart disease and mortality due to cancer , with adjustment for age , sex , body-mass index , physical-activity level , and other potential confounders . RESULTS During a median of 44 months of follow-up , there were 275 deaths . A higher degree of adherence to the Mediterranean diet was associated with a reduction in total mortality ( adjusted hazard ratio for death associated with a two-point increment in the Mediterranean-diet score , 0.75 [ 95 percent confidence interval , 0.64 to 0.87 ] ) . An inverse association with greater adherence to this diet was evident for both death due to coronary heart disease ( adjusted hazard ratio , 0.67 [ 95 percent confidence interval , 0.47 to 0.94 ] ) and death due to cancer ( adjusted hazard ratio , 0.76 [ 95 percent confidence interval , 0.59 to 0.98 ] ) . Associations between individual food groups contributing to the Mediterranean-diet score and total mortality were generally not significant . CONCLUSIONS Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in total mortality CONTEXT Higher adherence to a Mediterranean-type diet is linked to lower risk for mortality and chronic diseases , but its association with cognitive decline is unclear . OBJECTIVE To investigate the association of a Mediterranean diet with change in cognitive performance and risk for dementia in elderly French persons . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 1410 adults ( > or = 65 years ) from Bordeaux , France , included in the Three-City cohort in 2001 - 2002 and reexamined at least once over 5 years . Adherence to a Mediterranean diet ( scored as 0 to 9 ) was computed from a food frequency question naire and 24-hour recall . MAIN OUTCOME MEASURES Cognitive performance was assessed on 4 neuropsychological tests : the Mini-Mental State Examination ( MMSE ) , Isaacs Set Test ( IST ) , Benton Visual Retention Test ( BVRT ) , and Free and Cued Selective Reminding Test ( FCSRT ) . Incident cases of dementia ( n = 99 ) were vali date d by an independent expert committee of neurologists . RESULTS Adjusting for age , sex , education , marital status , energy intake , physical activity , depressive symptomatology , taking 5 medications/d or more , apolipoprotein E genotype , cardiovascular risk factors , and stroke , higher Mediterranean diet score was associated with fewer MMSE errors ( beta = -0.006 ; 95 % confidence interval [ CI ] , -0.01 to -0.0003 ; P = .04 for 1 point of the Mediterranean diet score ) . Performance on the IST , BVRT , or FCSRT over time was not significantly associated with Mediterranean diet adherence . Greater adherence as a categorical variable ( score 6 - 9 ) was not significantly associated with fewer MMSE errors and better FCSRT scores in the entire cohort , but among individuals who remained free from dementia over 5 years , the association for the highest compared with the lowest group was significant ( adjusted for all factors , for MMSE : beta = -0.03 ; 95 % CI , -0.05 to -0.001 ; P = .04 ; for FCSRT : beta = 0.21 ; 95 % CI , 0.008 to 0.41 ; P = .04 ) . Mediterranean diet adherence was not associated with the risk for incident dementia ( fully adjusted model : hazard ratio , 1.12 ; 95 % CI , 0.60 to 2.10 ; P = .72 ) , although power to detect a difference was limited . CONCLUSIONS Higher adherence to a Mediterranean diet was associated with slower MMSE cognitive decline but not consistently with other cognitive tests . Higher adherence was not associated with risk for incident dementia IMPORTANCE Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline , a strong risk factor for development of dementia . Epidemiologic studies suggest that a Mediterranean diet , an antioxidant-rich cardioprotective dietary pattern , delays cognitive decline , but clinical trial evidence is lacking . OBJECTIVE To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet . DESIGN , SETTING , AND PARTICIPANTS Parallel-group r and omized clinical trial of 447 cognitively healthy volunteers from Barcelona , Spain ( 233 women [ 52.1 % ] ; mean age , 66.9 years ) , at high cardiovascular risk were enrolled into the Prevención con Dieta Mediterránea nutrition intervention trial from October 1 , 2003 , through December 31 , 2009 . All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study . INTERVENTIONS Participants were r and omly assigned to a Mediterranean diet supplemented with extravirgin olive oil ( 1 L/wk ) , a Mediterranean diet supplemented with mixed nuts ( 30 g/d ) , or a control diet ( advice to reduce dietary fat ) . MAIN OUTCOMES AND MEASURES Rates of cognitive change over time based on a neuropsychological test battery : Mini-Mental State Examination , Rey Auditory Verbal Learning Test ( RAVLT ) , Animals Semantic Fluency , Digit Span subtest from the Wechsler Adult Intelligence Scale , Verbal Paired Associates from the Wechsler Memory Scale , and the Color Trail Test . We used mean z scores of change in each test to construct 3 cognitive composites : memory , frontal ( attention and executive function ) , and global . RESULTS Follow-up cognitive tests were available in 334 participants after intervention ( median , 4.1 years ) . In multivariate analyses adjusted for confounders , participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT ( P = .049 ) and Color Trail Test part 2 ( P = .04 ) compared with controls ; no between-group differences were observed for the other cognitive tests . Similarly adjusted cognitive composites ( mean z scores with 95 % CIs ) for changes above baseline of the memory composite were 0.04 ( -0.09 to 0.18 ) for the Mediterranean diet plus olive oil , 0.09 ( -0.05 to 0.23 ; P = .04 vs controls ) for the Mediterranean diet plus nuts , and -0.17 ( -0.32 to -0.01 ) for the control diet . Respective changes from baseline of the frontal cognition composite were 0.23 ( 0.03 to 0.43 ; P = .003 vs controls ) , 0.03 ( -0.25 to 0.31 ) , and -0.33 ( -0.57 to -0.09 ) . Changes from baseline of the global cognition composite were 0.05 ( -0.11 to 0.21 ; P = .005 vs controls ) for the Mediterranean diet plus olive oil , -0.05 ( -0.27 to 0.18 ) for the Mediterranean diet plus nuts , and -0.38 ( -0.57 to -0.18 ) for the control diet . All cognitive composites significantly ( P < .05 ) decreased from baseline in controls . CONCLUSIONS AND RELEVANCE In an older population , a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N35739639 CONTEXT Both higher adherence to a Mediterranean-type Output:	Based on the findings and the limitations in study design , we conclude that adherence to the MD is associated with better cognitive performance . However , it should be noted that the majority of findings come from epidemiologic studies that provide evidence for a correlation between the MD and cognition but not for a cause- and -effect relation .
MS21635	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : We examined intraoperative microembolic signals ( GME ) , inflammatory response , hemolysis , perioperative regional cerebral oxygen saturation ( rSO2 ) , myocardial protection and desorbed protein amount on oxygenator fibers in high-risk patients undergoing coronary revascularization ( CABG ) with minimized and conventional cardiopulmonary bypass ( CPB ) . Methods : Over a ten-month period , 40 Euroscore 6 + patients undergoing CABG were prospect ively r and omized to one of the two perfusion protocol s ( N=20 ) : Group 1 : minimized extracorporeal circuits ( Mini-CPB ) ( ROCsafe MPC , Terumo , Ann Arbor , MI , USA ) and Group 2 : conventional extracorporeal circuits ( CECC ) ( Capiox SX18 , Terumo , USA ) . Serum creatinine kinase-MB ( CKMB ) , free hemoglobin , interleukin-6 ( IL-6 ) and C3a levels were measured . Blood sample s were collected at T1 : following induction of anesthesia ; T2 : thromboelastography control ; T3:15 min after commencement of CPB ; T4 : before cessation of CPB ; T5 : 15 min after protamine reversal and T6 : ICU . Results : Serum IL-6 levels were significantly lower in the Mini-CPB group at T4 and T5 and C3a levels were significantly less in the Mini-CPB group at T3 , T4 and T5 vs. CECC ( p<0.01 ) . CKMB levels in coronary sinus blood demonstrated well preserved myocardium in the Mini-CPB group . Percentage expression of neutrophil CD11b/CD18 levels were significantly lower in the Mini-CPB group at T4 and T5 ( p<0.05 ) . There were no significant differences in air h and ling characteristics or free plasma hemoglobin levels in either circuit . rSO2 measurements were significantly better at T3 and T4 in the Mini-CPB vs. CECC ( p<0.05 ) and always higher in the Mini-CPB during follow-up . Blood protein adsorption analysis of oxygenator membranes demonstrated a significantly increased amount of microalbumin on CECC fibers ( p<0.05 ) . Conclusion : Mini-CPB provided a comfort and safety level similar to conventional control via satisfactory air h and ling , attenuated inflammatory response and hemodilution , with a better clinical outcome in patients undergoing high-risk CABG In this prospect i ve cohort study we addressed the clinical impact of a reduced anticoagulation protocol on the hospital outcome of patients undergoing coronary revascularization with cardiopulmonary bypass . 364 consecutive low to moderate risk patients scheduled for elective isolated coronary operations were admitted to the study . 184 patients ( Control Group ) received conventional open circuits and full systemic anticoagulation ( target activated clotting time 480 seconds ) ; 180 patients ( Intraoperative ECMO group ) received closed , phosphorylcholine coated circuits and a reduced systemic heparin dose ( target activated clotting time 320 seconds ) . Patients of the Intraoperative ECMO group had less requirement for allogeneic blood products ( odds ratio 0.55 , 95 % confidence interval 0.34–0.92 , p= 0.02 ) , a significant containment of blood loss ( 374 ± 278 mL vs. 463 ± 321 mL in Control group , p= 0.005 ) a lower postoperative peak serum creatinine levels ( 1.19 ± 0.48 mg/dL vs. 1.41 ± 0.94 mg/dL in Control group , p= 0.048 ) , and a significant lower rate of severe morbidity ( odds ratio 0.27 , 95 % confidence interval 0.09–0.81 , p= 0.02 ) . A reduction of systemic anticoagulation is feasible with a non-heparin-bonded , closed biocompatible circuit , and results in a significant improvement of the outcome of low to moderate risk coronary patients PURPOSE Inflammation and coagulation disturbances are common consequences of cardiopulmonary bypass ( CPB ) . Recently , miniaturized closed CPB circuits without cardiotomy suction and venous reservoir have been proposed to reduce complication rates . We compared outcomes with conventional ( CCPB ) and miniaturized cardiopulmonary bypass ( MCPB ) after coronary artery bypass operations ( CABG ) with respect to inflammation and coagulation . DESCRIPTION Thirty patients ( 23 % female ; aged 67.9 + /- 9.0 years ) were prospect ively r and omly assigned to undergo isolated CABG with CCPB or MCPB . Conventional CPB had a pump prime of 1 , 600 mL. Miniaturized CPB consisted of a centrifugal pump , arterial filter , heparinized tubing , and oxygenator with a priming volume of 800 mL. Shed blood was removed by a cell-saving device and reinfused . Measurements included interleukin (IL)-2 receptor , IL-6 , IL-10 , tumor necrosis factor receptor 55 and 75 , C reactive protein , leukocyte differentiation , d-dimers , fibrinogen , and thrombocytes at six time points . EVALUATION In both groups no major complication occurred . However , two dangerous air leaks occurred in the closed MCPB circuit , demonstrating the narrow safety margins . Operative h and ling was also more difficult owing to limitations in venting and fluid management . International normalized ratio ( p = 0.03 ) and antithrombin III ( p = 0.04 ) levels were elevated during CPB in the CCPB group , most likely owing to differences of the intraoperative anticoagulation management . Repeated measures analysis revealed that not a single parameter of inflammation or clinical outcome showed significant differences among groups . CONCLUSIONS Use of a MCPB affected inflammation and coagulation variables only marginally and did not lead to clinical relevant changes as assessed by blood loss , need for blood products , and intensive care unit and clinical stays . However , safety margins for volume loss , air emboli , and weaning from CPB decrease , because of the closed MCPB circuit Objectives . Cardiopulmonary bypass ( CPB ) is known to cause the systemic inflammatory reaction after cardiac surgery . New coated and closed loop circuit systems may reduce this inflammation response and improve the surgical outcome . This study was design ed to evaluate the safety and efficacy of the mini-extracorporeal circulation system ( ECC.O ) in CABG patients . Design . Forty patients undergoing elective coronary surgery were r and omized into two groups , the ECC.O group and the st and ard CPB group . Routine hemodynamic monitoring and biochemical measurements were registered according to the hospital practice . Results . The clinical outcome of the patients was similar in both groups . There were no significant differences between the groups in the duration of intubation following surgery , the length of intensive care unit-stay or the total hospital stay . The haemoglobin level was significantly higher ( p=0.0069 ) during and after the perfusion in the ECC.O group . Conclusions . The ECC.O system can be safely used in CABG patients and it maintains haemoglobin level better than conventional CPB OBJECTIVE Coronary artery bypass grafting with cardiopulmonary bypass carries a risk for neurologic complications because of cerebral hypoperfusion and microembolization . The basic goals of a novel closed minimized extracorporeal circulation are to prevent excessive hemodilution and to avoid blood-air interface . The aim of this prospect i ve r and omized study was to determine the effect of using the minimized extracorporeal circulation system compared with open conventional extracorporeal circulation on cerebral tissue oxygenation and microembolization . METHODS Forty patients undergoing coronary artery bypass grafting ( 20 in each group ) were continuously monitored for changes in cerebral oxygenated hemoglobin and tissue oxygenation index by using near-infrared spectroscopy . Total microembolic count and gaseous embolic count in both median cerebral arteries were monitored with multifrequency transcranial Doppler instrumentation . RESULTS In the conventional extracorporeal circulation group there was a highly significant reduction in both cerebral oxygenated hemoglobin and tissue oxygenation index from the start to the end of cardiopulmonary bypass ( P < .01 ) . The rate of decrease in cerebral oxygenated hemoglobin after aortic cannulation was faster in the conventional extracorporeal circulation group ( F test = 9.03 , P < .001 ) . No significant changes with respect to cerebral oxygenated hemoglobin or tissue oxygenation index occurred in the minimized extracorporeal circulation group , except at the beginning of rewarming ( P < .01 ) . Total embolic count , as well as gaseous embolic count , in the left and right median cerebral arteries was significantly lower in the minimized extracorporeal circulation group ( all P < .05 ) . Postoperative bleeding was greater ( P < .05 ) and the transfusion rate was higher ( P < .05 ) in the conventional extracorporeal circulation group . CONCLUSIONS Use of closed minimized cardiopulmonary bypass compared with conventional open cardiopulmonary bypass preserves cerebral tissue oxygenation and reduces cerebral microembolization Neutrophil gelatinase-associated lipocalin ( NGAL ) has been implicated as an early predictive urinary biomarker of ischemic acute kidney injury ( AKI ) . The aim of this study was to compare the effects of miniaturized cardiopulmonary bypass system ( MCPB ) vs. st and ard cardiopulmonary bypass system ( SCPB ) system on kidney tissue in patients undergoing myocardial revascularization using urinary NGAL levels as an early marker for renal injury . Sixty consecutive patients who underwent myocardial revascularization were studied prospect ively . An SCPB was used in 30 patients ( group A ) and MCPB was used in 30 patients ( group B ) . The SCPB group but not the MCPB group showed a significant NGAL concentration increase from preoperative during the 1st postoperative day ( 169.0+/-163.6 ng/ml in the SCPB group vs. 94.1+/-99.4 ng/ml in the MCPB group , P<0.05 , respectively ) . Two patients in the SCPB group developed AKI and underwent renal replacement therapy ; no patient in MCPB developed AKI . The MCPB system is safe in routine clinical use . Kidney function is better protected during MCPB as demonstrated by NGAL levels . NGAL represents an early biomarker of renal failure in patients undergoing cardiac surgery and the valuation of its concentration can aid in medical decision-making OBJECTIVE Minimal extracorporeal circulation ( mini-ECC ) is a new technology , consisting of a centrifugal pump , an oxygenator , and a modified suction system . The main advantage of mini-ECC is the reduction of tubing length ( reduction of the priming volume ) . Additional beneficial effects are a decrease of coagulation cascade and a reduction of blood transfusion in patients undergoing coronary artery bypass grafting ( CABG ) surgery . We compared the intraoperative and early postoperative myocardial damage and outcome of patients who underwent CABG surgery with conventional cardiopulmonary bypass ( CPB ) or mini-ECC . METHODS One hundred and thirty-six consecutive patients who underwent isolated CABG surgery at our institution were prospect ively studied . Fifty-four patients ( 39.7 % ) were operated with mini-ECC . Patient characteristics were similar in both groups . The most interesting intraoperative details as well as in-hospital outcome were assessed . RESULTS There was no difference in mortality between the two groups . Cross-clamping time was similar in both groups ( p = 0.07 ) . Defibrillation was required in one patient in the mini-ECC group ( 1.9 % ) and in 38 patients ( 46.3 % ) in the CPB group ( p < 0.001 ) . In the mini-ECC group , the requirement of inotropic support and incidence of atrial fibrillation was significantly lower than in the CPB group . Postoperative creatine kinase isoenzyme MB ( CK-MB ) and cardiac Troponin I ( cTnI ) were significantly lower in the mini-ECC group ( p < 0.05 ) . Duration of ventilation , length of stay in the intensive care unit and total hospitalization time were significantly shorter in patients operated with mini-ECC ( p < 0.05 ) . CONCLUSION Mini-ECC is a safe procedure and is followed by a diminished release of CK-MB and cTnI than after CPB . Postoperative recovery is accelerated following mini-ECC and there is a significantly lower incidence of postoperative atrial fibrillation BACKGROUND The purpose of this study was to evaluate the safety and clinical results of aortic valve replacement performed with minimally invasive closed circuit extracorporeal circulation technique ( MECC system ) versus st and ard cardiopulmonary bypass . METHODS Forty consecutive patients undergoing isolated aortic valve replacement at a single institution were r and omly assigned to either miniaturized closed circuit cardiopulmonary bypass with the Maquet-Cardiopulmonary ( Rastatt , Germany ) minimal extracorporeal circulation ( MECC ) system ( study group B , n = 17 ) or st and ard cardiopulmonary bypass ( control group A , n = 23 ) . The MECC system is Output:	CONCLUSIONS Use of MECC in heart surgery result ed in improved short-term outcome as reflected by reduced mortality and morbidity compared with conventional extracorporeal circulation
MS21636	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Pathological formation of reactive oxygen species within the coronary circulation has been hypothesized to mediate some clinical manifestations of ischemic heart disease ( IHD ) by interfering with physiological regulation of coronary tone . To determine the degree to which coronary tone responds to acute changes in ambient levels of oxidants and antioxidants in vivo in a clinical setting , we measured the effect of an acute oxidative stress ( breathing 100 % oxygen ) on coronary capacitance artery diameter ( quantitative angiography ) and blood flow velocity through the coronary microcirculation ( intracoronary Doppler ultrasonography ) before and after treatment with the antioxidant vitamin C ( 3-g intravenous infusion ) in 12 IHD patients undergoing a clinical coronary interventional procedure . Relative to room air breathing , 100 % oxygen breathing promptly reduced coronary blood flow velocity by 20 % and increased coronary resistance by 23 % , without significantly changing the diameter of capacitance arteries . Vitamin C administration promptly restored coronary flow velocity and resistance to a slightly suprabasal level , and it prevented the reinduction of coronary constriction with rechallenge with 100 % oxygen . This suggests that acute oxidative stress produces prompt and substantial changes in coronary resistance and blood flow in a clinical setting in patients with IHD , and it suggests that these changes are mediated by vitamin C-quenchable substances acting on the coronary microcirculation . This observation may have relevance for clinical practice OBJECTIVES We sought to determine whether abnormal myocardial blood flow ( MBF ) responses to the cold pressor test ( CPT ) in patients with various risk factors may involve different mechanisms that could lead to varying responses of short- and long-term administration of antioxidants . BACKGROUND There is a growing body of evidence that increased vascular production of reactive oxygen species markedly reduces the bioavailability of endothelium-derived nitric oxide , leading to impaired vasodilator function . It is unknown whether increased oxidative stress is the prevalent mechanism underlying endothelial dysfunction in patients with different coronary risk factors . METHODS Fifty patients with normal coronary angiograms were studied . The MBF responses to CPT was determined by means of positron emission tomography before and after intravenous infusion of 3 g vitamin C or saline ( placebo ) , as well as after 3 months and 2 years of 2 g vitamin C or placebo supplementation daily . RESULTS In hypertensive patients , the change in MBF ( DeltaMBF ) was not modified significantly by short-term vitamin C administration challenges ( 0.20 + /- 0.20 ml/g/min ; p = NS ) but was significantly increased after three months and two years of treatment with vitamin C versus baseline ( 0.58 + /- 0.27 and 0.63 + /- 0.17 vs. 0.14 + /- 0.18 ml/g/min ; both p < or = 0.001 ) . In smokers , DeltaMBF in response to CPT was significantly increased after short-term vitamin C infusion and long-term vitamin C treatment ( 0.52 + /- 0.10 , 0.54 + /- 0.13 , 0.50 + /- 0.07 vs. -0.08 + /- 0.10 ml/g/min ; all p < or = 0.001 ) . In hypercholesterolemic patients , no improvement in DeltaMBF during CPT was observed after short- and long-term vitamin C treatment ( 0.05 + /- 0.14 , 0.08 + /- 0.18 , 0.02 + /- 0.19 vs. 0.08 + /- 0.16 ml/g/min ; p = NS ) . The CPT-induced DeltaMBF in hypertensive patients and smokers after follow-up was significant as compared with placebo and control subjects ( p < or = 0.001 ) . CONCLUSIONS The present study revealed marked heterogeneous responses in MBF changes to short- and long-term vitamin C treatment in patients with various risk factors , which highlights the quite complex nature underlying abnormal coronary vasomotion CONTEXT Basic research and observational studies suggest vitamin E or vitamin C may reduce the risk of cardiovascular disease . However , few long-term trials have evaluated men at initially low risk of cardiovascular disease , and no previous trial in men has examined vitamin C alone in the prevention of cardiovascular disease . OBJECTIVE To evaluate whether long-term vitamin E or vitamin C supplementation decreases the risk of major cardiovascular events among men . DESIGN , SETTING , AND PARTICIPANTS The Physicians ' Health Study II was a r and omized , double-blind , placebo-controlled factorial trial of vitamin E and vitamin C that began in 1997 and continued until its scheduled completion on August 31 , 2007 . There were 14,641 US male physicians enrolled , who were initially aged 50 years or older , including 754 men ( 5.1 % ) with prevalent cardiovascular disease at r and omization . INTERVENTION Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily . MAIN OUTCOME MEASURES A composite end point of major cardiovascular events ( nonfatal myocardial infa rct ion , nonfatal stroke , and cardiovascular disease death ) . RESULTS During a mean follow-up of 8 years , there were 1245 confirmed major cardiovascular events . Compared with placebo , vitamin E had no effect on the incidence of major cardiovascular events ( both active and placebo vitamin E groups , 10.9 events per 1000 person-years ; hazard ratio [ HR ] , 1.01 [ 95 % confidence interval { CI } , 0.90 - 1.13 ] ; P = .86 ) , as well as total myocardial infa rct ion ( HR , 0.90 [ 95 % CI , 0.75 - 1.07 ] ; P = .22 ) , total stroke ( HR , 1.07 [ 95 % CI , 0.89 - 1.29 ] ; P = .45 ) , and cardiovascular mortality ( HR , 1.07 [ 95 % CI , 0.90 - 1.28 ] ; P = .43 ) . There also was no significant effect of vitamin C on major cardiovascular events ( active and placebo vitamin E groups , 10.8 and 10.9 events per 1000 person-years , respectively ; HR , 0.99 [ 95 % CI , 0.89 - 1.11 ] ; P = .91 ) , as well as total myocardial infa rct ion ( HR , 1.04 [ 95 % CI , 0.87 - 1.24 ] ; P = .65 ) , total stroke ( HR , 0.89 [ 95 % CI , 0.74 - 1.07 ] ; P = .21 ) , and cardiovascular mortality ( HR , 1.02 [ 95 % CI , 0.85 - 1.21 ] ; P = .86 ) . Neither vitamin E ( HR , 1.07 [ 95 % CI , 0.97 - 1.18 ] ; P = .15 ) nor vitamin C ( HR , 1.07 [ 95 % CI , 0.97 - 1.18 ] ; P = .16 ) had a significant effect on total mortality but vitamin E was associated with an increased risk of hemorrhagic stroke ( HR , 1.74 [ 95 % CI , 1.04 - 2.91 ] ; P = .04 ) . CONCLUSIONS In this large , long-term trial of male physicians , neither vitamin E nor vitamin C supplementation reduced the risk of major cardiovascular events . These data provide no support for the use of these supplements for the prevention of cardiovascular disease in middle-aged and older men . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00270647 One gram of ascorbic acid ( Vitamin C ) administered r and omly to a group of healthy young people ( aged 29 ± 5 years ) produced a significant mean fall in serum cholesterol of 16 per cent within two months . A similar supplement to a group of healthy older people ( aged 58 ± 3 years ) produced a significant mean fall in serum cholesterol of 14 per cent but required six to 12 months ' administration . Serial observations on a mixed age group of healthy people ( aged 38 ± 12 years ) over one calendar year revealed a seasonal fluctuation in serum cholesterol , the lowest levels being in summer ( June 5.5 ± 0.7 mmols/l ) and the highest levels in winter ( January 6.4 ± 0.8 mmols/l ) , a significant rise of 16 per cent . These changes showed an inverse relationship with the leucocyte and serum ascorbic acid levels which also revealed a seasonal fluctuation , the months April/September being higher than the months October/March . The administration of 1 g of ascorbic acid per day throughout the year abolished the winter rise in serum cholesterol levels . These results are discussed in the light of the relationship between cholesterol and vascular disease and the observations by Sir Richard Doll that lowering the cholesterol level , whether achieved by drugs or diet , results in a reduction in morbidity from myocardial infa rct ion Background —Self-selected supplementation of vitamin E has been associated with reduced coronary events and atherosclerotic progression , but the evidence from clinical trials is controversial . In the first 3 years of the ASAP trial , the supplementation with 136 IU of vitamin E plus 250 mg of slow-release vitamin C twice daily slowed down the progression of carotid atherosclerosis in men but not women . This article examines the 6-year effect of supplementation on common carotid artery ( CCA ) intima-media thickness ( IMT ) . Methods and Results —The subjects were 520 smoking and nonsmoking men and postmenopausal women aged 45 to 69 years with serum cholesterol ≥5.0 mmol/L ( 193 mg/dL ) , 440 ( 84.6 % ) of whom completed the study . Atherosclerotic progression was assessed ultrasonographically . In covariance analysis in both sexes , supplementation reduced the main study outcome , the slope of mean CCA-IMT , by 26 % ( 95 % CI , 5 to 46 , P = 0.014 ) , in men by 33 % ( 95 % CI , 4 to 62 , P = 0.024 ) and in women by 14 % ( not significant ) . In both sexes combined , the average annual increase of the mean CCA-IMT was 0.014 mm in the unsupplemented and 0.010 mm in the supplemented group ( 25 % treatment effect , 95 % CI , 2 to 49 , P = 0.034 ) . In men , this treatment effect was 37 % ( 95 CI , 4 to 69 , P = 0.028 ) . The effect was larger in subjects with either low baseline plasma vitamin C levels or CCA plaques . Vitamin E had no effect on HDL cholesterol . Conclusions —These data replicate our 3-year findings confirming that the supplementation with combination of vitamin E and slow-release vitamin C slows down atherosclerotic progression in hypercholesterolemic persons Background The grading of recommendation , assessment , development and evaluation ( GRADE ) approach is widely implemented in health technology assessment and guideline development organisations throughout the world . GRADE provides a transparent approach to reaching judgements about the quality of evidence on the effects of a health care intervention , but is complex and therefore challenging to apply in a consistent manner . Methods We developed a checklist to guide the research er to extract the data required to make a GRADE assessment . We applied the checklist to 29 meta-analyses of r and omised controlled trials on the effectiveness of health care interventions . Two review ers used the checklist for each paper and used these data to rate the quality of evidence for a particular outcome . Results For most ( 70 % ) checklist items , there was good agreement between review ers . The main problems were for items relating to indirectness where considerable judgement is required . Conclusions There was consistent agreement between review ers on most items in the checklist . The use of this checklist may be an aid to improving the consistency and reproducibility of GRADE assessment s , particularly for inexperienced users or in rapid review s without the re sources to conduct assessment s by two research ers independently OBJECTIVES To study the efficacy of vitamin E and C supplementation on the progression of carotid atherosclerosis , hypothesizing an enhanced preventive effect in men and in smokers and synergism between vitamins . DESIGN AND SUBJECTS Double-masked two-by-two factorial trial , r and omization in four strata ( by gender and smoking status ) to receive twice daily either 91 mg ( 136 IU ) of d-alpha-tocopherol , 250 mg of slow-release vitamin C , a combination of these or placebo for three years . A r and omized sample of 520 smoking and nonsmoking men and postmenopausal women aged 45 - 69 years with serum cholesterol > /= 5.0 mmol L-1 were studied . SETTING The population of the city Output:	There is limited low- and very low- quality evidence currently on the effect of vitamin C supplementation and risk of CVD risk factors
MS21637	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Enzalutamide ( formerly called MDV3100 ) targets multiple steps in the and rogen-receptor-signaling pathway , the major driver of prostate-cancer growth . We aim ed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy . METHODS In our phase 3 , double-blind , placebo-controlled trial , we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity . We r and omly assigned them , in a 2:1 ratio , to receive oral enzalutamide at a dose of 160 mg per day ( 800 patients ) or placebo ( 399 patients ) . The primary end point was overall survival . RESULTS The study was stopped after a planned interim analysis at the time of 520 deaths . The median overall survival was 18.4 months ( 95 % confidence interval [ CI ] , 17.3 to not yet reached ) in the enzalutamide group versus 13.6 months ( 95 % CI , 11.3 to 15.8 ) in the placebo group ( hazard ratio for death in the enzalutamide group , 0.63 ; 95 % CI , 0.53 to 0.75 ; P<0.001 ) . The superiority of enzalutamide over placebo was shown with respect to all secondary end points : the proportion of patients with a reduction in the prostate-specific antigen ( PSA ) level by 50 % or more ( 54 % vs. 2 % , P<0.001 ) , the soft-tissue response rate ( 29 % vs. 4 % , P<0.001 ) , the quality -of-life response rate ( 43 % vs. 18 % , P<0.001 ) , the time to PSA progression ( 8.3 vs. 3.0 months ; hazard ratio , 0.25 ; P<0.001 ) , radiographic progression-free survival ( 8.3 vs. 2.9 months ; hazard ratio , 0.40 ; P<0.001 ) , and the time to the first skeletal-related event ( 16.7 vs. 13.3 months ; hazard ratio , 0.69 ; P<0.001 ) . Rates of fatigue , diarrhea , and hot flashes were higher in the enzalutamide group . Seizures were reported in five patients ( 0.6 % ) receiving enzalutamide . CONCLUSIONS Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy . ( Funded by Medivation and Astellas Pharma Global Development ; AFFIRM Clinical Trials.gov number , NCT00974311 . ) While programmed cell death 1 ( PD-1 ) inhibitors have shown clear anti-tumor efficacy in several solid tumors , prior results in men with metastatic castration resistant prostate cancer ( mCRPC ) showed no evidence of activity . Here we report unexpected antitumor activity seen in mCRPC patients treated with the anti-PD-1 antibody pembrolizumab . Patients with evidence of progression on enzalutamide were treated with pembrolizumab 200 mg IV every 3 weeks for 4 doses ; pembrolizumab was added to st and ard dose enzalutamide . Three of the first ten patients enrolled in this ongoing phase II trial experienced rapid prostate specific antigen ( PSA ) reductions to ≤ 0.2 ng/ml . Two of these three patients had measurable disease upon study entry ; both achieved a partial response . There were three patients with significant immune-related adverse events . One had grade 2 myositis , one had grade 3 hypothyroidism , and one had grade 2 hypothyroidism . None of these patients had a response . Two of the three responders had a baseline tumor biopsy . Immunohistochemistry from those biopsies showed the presence of CD3 + , CD8 + , and CD163 + leukocyte infiltrates and PD-L1 expression . Genetic analysis of the two responders revealed markers of microsatellite instability in one . The surprising and robust responses seen in this study should lead to re-examination of PD-1 inhibition in prostate cancer R and omised controlled trials and population -based observational research : partners in the evolution of medical OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Purpose : To evaluate the efficacy , safety , biomarkers , and pharmacokinetics of rilotumumab , a fully human , monoclonal antibody against hepatocyte growth factor (HGF)/scatter factor , combined with mitoxantrone and prednisone ( MP ) in patients with castration-resistant prostate cancer ( CRPC ) . Experimental Design : This double-blinded phase II study r and omized ( 1:1:1 ) patients with progressive , taxane-refractory CRPC to receive MP ( 12 mg/m2 i.v . day 1 , 5 mg twice a day orally days 1–21 , respectively ) plus 15 mg/kg rilotumumab , 7.5 mg/kg rilotumumab , or placebo ( i.v . day 1 ) every 3 weeks . The primary endpoint was overall survival ( OS ) . Results : One hundred and forty-four patients were r and omized . Median OS was 12.2 versus 11.1 months [ HR , 1.10 ; 80 % confidence interval ( CI ) , 0.82–1.48 ] in the combined rilotumumab versus control arms . Median progression-free survival was 3.0 versus 2.9 months ( HR , 1.02 ; 80 % CI , 0.79–1.31 ) . Treatment appeared well tolerated with peripheral edema ( 24 % vs. 8 % ) being more common with rilotumumab . A trend toward unfavorable OS was observed in patients with high tumor MET expression regardless of treatment . Soluble MET levels increased in all treatment arms . Total HGF levels increased in the rilotumumab arms . Rilotumumab showed linear pharmacokinetics when co-administered with MP . Conclusions : Rilotumumab plus MP had manageable toxicities and showed no efficacy improvements in this estimation study . High tumor MET expression may identify patients with CRPC with poorer prognosis . Clin Cancer Res ; 19(1 ) ; 215–24 . © 2012 AACR BACKGROUND Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced , hormone-refractory prostate cancer , but it does not improve survival . We compared such treatment with docetaxel plus prednisone in men with this disease . METHODS From March 2000 through June 2002 , 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and were r and omly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks , 75 mg of docetaxel per square meter every three weeks , or 30 mg of docetaxel per square meter weekly for five of every six weeks . The primary end point was overall survival . Secondary end points were pain , prostate-specific antigen ( PSA ) levels , and the quality of life . All statistical comparisons were against mitoxantrone . RESULTS As compared with the men in the mitoxantrone group , men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 ( 95 percent confidence interval , 0.62 to 0.94 ; P=0.009 by the stratified log-rank test ) and those given weekly docetaxel had a hazard ratio for death of 0.91 ( 95 percent confidence interval , 0.75 to 1.11 ; P=0.36 ) . The median survival was 16.5 months in the mitoxantrone group , 18.9 months in the group given docetaxel every 3 weeks , and 17.4 months in the group given weekly docetaxel . Among these three groups , 32 percent , 45 percent , and 48 percent of men , respectively , had at least a 50 percent decrease in the serum PSA level ( P<0.001 for both comparisons with mitoxantrone ) ; 22 percent , 35 percent ( P=0.01 ) , and 31 percent ( P=0.08 ) had predefined reductions in pain ; and 13 percent , 22 percent ( P=0.009 ) , and 23 percent ( P=0.005 ) had improvements in the quality of life . Adverse events were also more common in the groups that received docetaxel . CONCLUSIONS When given with prednisone , treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain , serum PSA level , and quality of life , as compared with mitoxantrone plus prednisone BACKGROUND In the AFFIRM trial of patients with metastatic castration-resistant prostate cancer after progression with docetaxel treatment , enzalutamide significantly increased overall survival compared with placebo . Here we present the prospect ively defined analyses of some secondary endpoints , including occurrence of skeletal-related events , measures of pain control , and patient-reported health-related quality of life ( HRQoL ) . METHODS In this phase 3 , double-blind trial , patients were r and omly assigned ( 2:1 ) to receive enzalutamide 160 mg/day or placebo orally , stratified by ECOG baseline performance status ( 0 or 1 vs 2 ) and mean pain score ( Brief Pain Inventory-Short Form [ BPI-SF ] question 3 worst pain , score ≤3 vs ≥4 ) . Secondary endpoints were time to first skeletal-related event ( defined as radiation therapy or surgery to bone ) ; change from baseline to week 13 in pain severity and interference ; pain palliation and progression at week 13 ; time to pain progression ; overall improvement in HRQoL ; improvements in HRQoL domains ; and time to HRQoL deterioration . Analysis was done on the intention-to-treat population for each endpoint . AFFIRM is registered with Clinical Trials.gov , number NCT00974311 . FINDINGS Median time to first skeletal-related event in the enzalutamide ( n=800 ) and placebo ( n=399 ) groups was 16·7 months ( 95 % CI 14·6 to 19·1 ) and 13·3 months ( 95 % CI 9·9 to not yet reached ) , respectively ( hazard ratio [ HR ] 0·69 [ 95 % CI 0·57 - 0·84 ] ; p=0·0001 ) . Pain progression at week 13 occurred in 174 ( 28 % ) of 625 evaluable patients in the enzalutamide group versus 101 ( 39 % ) of 259 patients in the placebo group ( difference -11·2 % , 95 % CI -18·1 to -4·3 ; p=0·0018 ) . Median time to pain progression was not yet reached in the enzalutamide group ( 95 % CI not yet reached to not yet reached ) versus 13·8 ( 13·8 to not yet reached ) months in the placebo group ( HR 0·56 [ 95 % Output:	Overall , there is a growing body of evidence for post-docetaxel treatment options available in patients with mCRPC .
MS21638	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Objective : To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care . Design : A before and after pragmatic cluster r and omised controlled trial utilising a two by two incomplete block design . Setting : 60 general practice s in north east Engl and . Participants : General practitioners and practice nurses in the study practice s and their patients aged 18 or over with angina or asthma . Main outcome measures : Adherence to the guidelines , based on review of case notes and patient reported generic and condition specific outcome measures . Results : The computerised decision support system had no significant effect on consultation rates , process of care measures ( including prescribing ) , or any patient reported outcomes for either condition . Levels of use of the software were low . Conclusions : No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care . This was probably due to low levels of use of the software , despite the system being optimised as far as was technically possible . Even if the technical problems of producing a system that fully supports the management of chronic disease were solved , there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex , multiple conditions Objective To develop an empirically based framework of the aspects of r and omised controlled trials addressed by qualitative research . Design Systematic mapping review of qualitative research undertaken with r and omised controlled trials and published in peer- review ed journals . Data sources MEDLINE , Pre MEDLINE , EMBASE , the Cochrane Library , Health Technology Assessment , PsycINFO , CINAHL , British Nursing Index , Social Sciences Citation Index and ASSIA . Eligibility criteria Articles reporting qualitative research undertaken with trials published between 2008 and September 2010 ; health research , reported in English . Results 296 articles met the inclusion criteria . Articles focused on 22 aspects of the trial within five broad categories . Some articles focused on more than one aspect of the trial , totalling 356 examples . The qualitative research focused on the intervention being trialled ( 71 % , 254/356 ) ; the design , process and conduct of the trial ( 15 % , 54/356 ) ; the outcomes of the trial ( 1 % , 5/356 ) ; the measures used in the trial ( 3 % , 10/356 ) ; and the target condition for the trial ( 9 % , 33/356 ) . A minority of the qualitative research was undertaken at the pretrial stage ( 28 % , 82/296 ) . The value of the qualitative research to the trial itself was not always made explicit within the articles . The potential value included optimising the intervention and trial conduct , facilitating interpretation of the trial findings , helping trialists to be sensitive to the human beings involved in trials , and saving money by steering research ers towards interventions more likely to be effective in future trials . Conclusions A large amount of qualitative research undertaken with specific trials has been published , addressing a wide range of aspects of trials , with the potential to improve the endeavour of generating evidence of effectiveness of health interventions . Research ers can increase the impact of this work on trials by undertaking more of it at the pretrial stage and being explicit within their articles about the learning for trials and evidence -based practice Background Computer-based decision support has been effective in providing alerts for preventive care . Our objective was to determine whether a personalized asthma management computer-based decision support increases the quality of asthma management and reduces the rate of out-of-control episodes . Methods A cluster-r and omized trial was conducted in Quebec , Canada among 81 primary care physicians and 4447 of their asthmatic patients . Patients were followed from the first visit for 3–33 months . The physician control group used the Medical Office of the 21st century ( MOXXI ) system , an integrated electronic health record . A custom-developed asthma decision support system was integrated within MOXXI and was activated for physicians in the intervention group . Results At the first visit , 9.8 % ( intervention ) to 12.9 % ( control ) of patients had out-of-control asthma , which was defined as a patient having had an emergency room visit or hospitalization for respiratory-related problems and /or more than 250 doses of fast-acting β-agonist ( FABA ) dispensed in the past 3 months . By the end of the trial , there was a significant increase in the ratio of doses of inhaled corticosteroid use to fast-acting β-agonist ( 0.93 vs. 0.69 : difference : 0.27 ; 95 % CI : 0.02–0.51 ; P = 0.03 ) in the intervention group . The overall out-of-control asthma rate was 54.7 ( control ) and 46.2 ( intervention ) per 100 patients per year ( 100 PY ) , a non-significant rate difference of −8.7 ( 95 % CI : −24.7 , 7.3 ; P = 0.29 ) . The intervention ’s effect was greater for patients with out-of-control asthma at the beginning of the study , a group who accounted for 44.7 % of the 5597 out-of-control asthma events during follow-up , as there was a reduction in the event rate of −28.4 per 100 PY ( 95 % CI : −55.6 , −1.2 ; P = 0.04 ) compared to patients with in-control asthma at the beginning of the study ( −0.08 [ 95 % CI : −10.3 , 8.6 ; P = 0.86 ] ) . Discussion This study evaluated the effectiveness of a novel computer-assisted ADS system that facilitates systematic monitoring of asthma control status , follow-up of patients with out of control asthma , and evidence -based , patient-specific treatment recommendations . We found that physicians were more likely to use ADS for out-of-control patients , that in the majority of these patients , they were advised to add an inhaled corticosteroid or a leukotriene inhibitor to the patient s treatment regimen , and the intervention significantly increased the mean ratio of inhaled corticosteroids to FABA during follow-up . It also reduced the rate of out-of-control episodes during follow up among patients whose asthma was out-of-control at the time of study entry . Future research should assess whether coupling patient-specific treatment recommendations , automated follow-up , and home care with comparative feedback on quality and outcomes of care can improve guideline adoption and care outcomes . Conclusions A primary care-personalized asthma management system reduced the rate of out-of-control asthma episodes among patients whose asthma was poorly controlled at the study ’s onset . Trial Registration Clinical trials.gov Identifier : NCT00170248 http:// clinical OBJECTIVE Computer-based clinical decision support systems ( CDSSs ) vary greatly in design and function . Using a taxonomy that we had previously developed , we describe the characteristics of CDSSs reported in the literature . METHODS We search ed PubMed and the Cochrane Library for r and omized controlled trials ( RCTs ) published in English between 1998 and 2003 that evaluated CDSSs . We coded each CDSS using our taxonomy . RESULTS 58 studies met our inclusion criteria . The 74 reported CDSSs varied greatly in context of use , knowledge and data sources , nature of decision support offered , information delivery , and workflow impact . Two distinct subsets of CDSSs were seen : patient-directed systems that provided decision support for preventive care or health-related behaviors via mail or phone ( 38 % of systems ) , and inpatient systems targeting clinicians with online decision support and direct online execution of the recommendations ( 18 % ) . 84 % of the CDSSs required extra staffing for h and ling CDSS-related input or output . CONCLUSION Reported CDSSs are heterogeneous along many dimensions . Caution should be taken in generalizing the results of CDSS RCTs to different clinical or workflow setting Beta‐agonist overuse is associated with adverse outcomes in asthma , however , the relationships between different metrics of salbutamol use and future risk are uncertain . BACKGROUND US national guidelines recommend assessing short-acting beta-agonist ( SABA ) medication use as a marker of asthma severity and control . However , the relationship between recent SABA use and asthma exacerbations is not currently known . OBJECTIVE To evaluate the proximal relationship between the type and frequency of SABA use and asthma-related outcomes . METHODS We evaluated SABA use among patients with asthma ages 5 to 56 years who were members of a large health maintenance organization in southeast Michigan . Frequency of use was estimated from pharmacy data assessing the timing and amount of SABA fills . Cox proportional hazards models were used to examine the prospect i ve relationship between average daily SABA use for 3 months and outcomes associated with poor asthma control ( ie , oral corticosteroids use , asthma-related emergency department visits , and asthma-related hospitalizations ) . We separately accounted for SABA metered-dose inhaler ( MDI ) and SABA nebulizer use . RESULTS Of the 2,056 patients who met study criteria , 1,569 ( 76.3 % ) had used a SABA medication in their baseline year . After adjusting for potential confounders , SABA nebulizer use was associated with asthma-related emergency department visits ( adjusted hazard ratio [ aHR ] , 6.32 ; 95 % confidence interval [ CI ] , 2.38 to 16.80 ) and asthma-related hospitalizations ( aHR , 21.62 ; 95 % CI , 3.17 to 147.57 ) . In contrast , frequency of SABA MDI use was not associated with these outcomes . CONCLUSIONS Frequency of SABA use during a 3-month period was associated with poor asthma outcomes . The relationship with poor asthma outcomes was strongest for SABA nebulizer use , suggesting that the type of SABA used is also of prognostic importance PRIMARY OBJECTIVE To investigate whether computer decision support software used in the management of patients with asthma improves clinical outcomes . RESEARCH DESIGN R and omized controlled trial with practice s each reporting on 30 patients with asthma over a 6 month period . METHODS AND PROCEDURES 447 patients were r and omly selected from practice asthma registers managed by 17 general practice s from throughout the UK . Intervention practice s used the software during consultations with these patients throughout the study while control practice s did not . MAIN OUTCOMES AND RESULTS Practice consultations , acute exacerbations of asthma , hospital contacts , symptoms on assessment and medication use . A smaller proportion of patients within the intervention group initiated practice consultations for their asthma : 34 ( 22 % ) vs 111 ( 34 % ) , odds ratio ( OR ) = 0.59 , 95 % confidence interval ( CI ) ( 0.37 - 0.95 ) ; and suffered acute asthma exacerbations : 12 ( 8 % ) vs 57 ( 17 % ) , OR = 0.43 , 95 % CI = 0.21 - 0.85 six months after the introduction of the computer decision support software . There were no discernable differences in reported symptoms , maintenance prescribing or use of hospital services between the two groups . CONCLUSION The use of computer decision support software that implements guidelines during patient consultations may improve clinical outcomes for patients with asthma BACKGROUND Excessive use of short-acting β2-agonists ( SABA ) indicates impaired asthma control . OBJECTIVE To determine whether real-time outreach to excessive SABA users reduces SABA canister dispensings . METHODS After real-time determination of a seventh SABA canister dispensing in the prior 12 months by using informational pharmacy technology , 12 to 56 year old patients with physician-coded asthma and inhaled corticosteroid dispensing were block r and omized by prior asthma specialist care and medication step-care level into intervention ( n = 1001 ) and control groups ( n = 998 ) . Intervention included real-time letter notification to patients and an electronic message to their physician with management suggestions , including facilitated allergy referral for patients without prior asthma specialist care . The control group received this organization 's st and ard asthma care management without research contact . Frequency of the seventh SABA canister dispensing in the follow-up year was the primary outcome . RESULTS Compared with controls , intervention patients reached 7 SABA canister dispensings less frequently ( 50.7 % vs 57.1 % ; risk ratio 0.89 [ 95 % CI , 0.82 - 0.97 ] ; P = .007 ) and later ( hazard ratio 0.80 [ 95 % CI , 0.71 - 0.91 ; P < .001 ) . SABA canister dispensings ( mean ± SD ) were less in intervention ( 7.5 ± 4.9 canisters ) than controls ( 8.6 ± 5.3 canisters ) ( rate ratio 0.87 [ 95 % CI , 0.82 - 0.93 ] ; P < .001 ) . The intervention reduced the risk of ≥7 SABA canister dispensings in patients without specialist care compared with patients with specialist care in the prior 3 years ( P < .001 ) ( P = .04 for interaction by prior specialist care ) . Visits to allergists were more frequent for intervention patients ( 30.9 % ) than for control patients ( 16.8 % ) ( risk ratio 1.83 [ 95 % CI , 1.54 - 2.16 ] ; P < .001 ) . Asthma exacerbations were unaffected . Output:	There is some evidence that electronic alerts reduce excessive prescribing of SABAs , when delivered as part of a multicomponent intervention in an integrated health care system .
MS21639	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In the current work we asked whether executive function , as measured by tests of working memory capacity , might benefit from an acute bout of exercise and , more specifically , whether individuals who are lower or higher in working memory to begin with would be more or less affected by an exercise manipulation . Healthy adults completed working memory measures in a nonexercise ( baseline ) session and immediately following a 30-min self-paced bout of exercise on a treadmill ( exercise session ) . Sessions were conducted 1 week apart and session order was counterbalanced across participants . A significant Session x Working Memory interaction was obtained such that only those individuals lowest in working memory benefited from the exercise manipulation . This work suggests that acute bouts of exercise may be most beneficial for healthy adults whose cognitive performance is generally the lowest , and it demonstrates that the impact of exercise on cognition is not uniform across all individuals The effects of acute aerobic exercise on cognitive functions in humans have been the subject of much investigation ; however , these studies are limited by several factors , including a lack of r and omized controlled design s , focus on only a single cognitive function , and testing during or shortly after exercise . Using a r and omized controlled design , the present study asked how a single bout of aerobic exercise affects a range of frontal- and medial temporal lobe-dependent cognitive functions and how long these effects last . We r and omly assigned 85 subjects to either a vigorous intensity acute aerobic exercise group or a video watching control group . All subjects completed a battery of cognitive tasks both before and 30 , 60 , 90 , or 120 min after the intervention . This battery included the Hopkins Verbal Learning Test-Revised , the Modified Benton Visual Retention Test , the Stroop Color and Word Test , the Symbol Digit Modalities Test , the Digit Span Test , the Trail Making Test , and the Controlled Oral Word Association Test . Based on these measures , composite scores were formed to independently assess prefrontal cortex- and hippocampal-dependent cognition . A three-way mixed Analysis of Variance was used to determine whether differences existed between groups in the change in cognitive function from pre- to post-intervention testing . Acute exercise improved prefrontal cortex- but not hippocampal-dependent functioning , with no differences found between delay groups . Vigorous acute aerobic exercise has beneficial effects on prefrontal cortex-dependent cognition and these effects can last for up to 2 hr after exercise Cognitive dysfunction has been repeatedly observed in major depressive disorder ( MDD ) , particularly in areas of attention , verbal and nonverbal learning and memory , and executive functioning . Exercise has been shown to improve cognitive outcomes in other population s , including age-associated cognitive decline , but has not to our knowledge been investigated as an augmentation strategy in depression . This study evaluated the effectiveness of exercise augmentation on cognitive performance in persons with MDD and residual symptoms that included cognitive complaints following initial treatment with a selective serotonin reuptake inhibitor ( SSRI ) . Participants enrolled in the Treatment with Exercise Augmentation for Depression ( TREAD ) study were r and omized to receive either a low or high dose exercise regimen . TREAD participants who provided informed consent for the current study completed Cambridge Neuropsychological Test Automated Battery measures assessing Attention , Visual Memory , Executive Function/Set-shifting and Working Memory , and Executive Function/Spatial Planning domains . Data were analyzed for 39 participants completing both baseline and Week 12 cognitive testing . Overall tests indicated a significant task × group × time interaction for the Executive Function/Set-shifting and Working Memory domain . Post-hoc tests indicated improvements in high dose exercisers ' spatial working memory , but decreases in spatial working memory and set-shifting outcomes in low dose exercisers . Both groups improved on measures of psychomotor speed , attention , visual memory and spatial planning . This study suggests a dose-response effect of exercise in specific executive function and working memory tasks among depressed persons with a partial response to SSRI and cognitive complaints , with some cognitive functions improving regardless of exercise dose Persistent long-term memory depends on successful stabilization and integration of new memories after initial encoding [ 1 , 2 ] . This consolidation process is thought to require neuromodulatory factors such as dopamine , noradrenaline , and brain-derived neurotrophic factor [ 3 - 7 ] . Without the release of such factors around the time of encoding , memories will decay rapidly [ 3 , 5 , 6 , 8 ] . Recent studies have shown that physical exercise acutely stimulates the release of several consolidation-promoting factors in humans [ 9 - 14 ] , raising the question of whether physical exercise can be used to improve memory retention [ 15 - 17 ] . Here , we used a single session of physical exercise after learning to exogenously boost memory consolidation and thus long-term memory . Three groups of r and omly assigned participants first encoded a set of picture-location associations . Afterward , one group performed exercise immediately , one 4 hr later , and the third did not perform any exercise . Participants otherwise underwent exactly the same procedures to control for potential experimental confounds . Forty-eight hours later , participants returned for a cued-recall test in a magnetic resonance scanner . With this design , we could investigate the impact of acute exercise on memory consolidation and retrieval-related neural processing . We found that performing exercise 4 hr , but not immediately , after encoding improved the retention of picture-location associations compared to the no-exercise control group . Moreover , performing exercise after a delay was associated with increased hippocampal pattern similarity for correct responses during delayed retrieval . Our results suggest that appropriately timed physical exercise can improve long-term memory and highlight the potential of exercise as an intervention in educational and clinical setting OBJECTIVE Physical exercise has been linked to higher cognitive functioning and enhanced brain plasticity in aging humans . The most consistent positive effects have been reported for executive functions associated with frontal brain regions . In rodents , however , running has been shown to induce functional and structural changes in the hippocampus , a brain region known to be important for memory . It is still a matter of debate which cognitive functions are susceptible to exercise and whether an increase in cardiovascular fitness is beneficial for cognitive functioning . Moreover , little is known about the impact of exercise on cognition in middle-aged humans . METHOD Sixty-eight sedentary men and women between 40 and 56 years of age were r and omly assigned to one of two training programs : aerobic endurance training ( cycling ) or nonendurance training ( stretching/coordination ) . Both groups exercised twice a week for six months . Additionally , a sedentary control group was tested . At baseline and after six months , episodic memory , perceptual speed , executive functions , and spatial reasoning were assessed with st and ardized psychometric tests , and all participants underwent a cardiovascular fitness test . RESULTS Significant improvements in memory were observed in both the cycling and the stretching/coordination group as compared with the sedentary control group . The improvement in episodic memory correlated positively with the increase in cardiovascular fitness . The stretching/coordination training particularly improved selective attention as compared with the cycling training . CONCLUSIONS The results suggest that cardiovascular fitness has beneficial effects even in high-functioning middle-aged participants , but that these benefits are very specific to memory functions rather than a wider range of cognitive functions Cognitive training has received a lot of attention recently , yielding findings that can be conflicting and controversial . In this paper , we present a novel approach to cognitive training based on complex motor activities . In a r and omized controlled design , participants were assigned to one of three conditions : aerobic exercise , working memory training or design ed sport -- an intervention specifically tailored to include both physical and cognitive dem and s. After training for eight weeks , the design ed sport group showed the largest gains in all cognitive measures , illustrating the efficacy of complex motor activities to enhance cognition . Design ed sport training also revealed impressive health benefits , namely decreased heart rate and blood pressure . In this period of skepticism over the efficacy of computerized cognitive training , we discuss the potential of ecological interventions targeting both cognition and physical fitness , and propose some possible applications This condensed review gives an overview about two method ological approaches to study the impact of physical activity on cognition in elderly , namely cross-sectional studies and r and omized controlled intervention studies with pre- and post- measures . Moreover , this review includes studies investigating different types of physical activity and their relation to cognitive functions in older age . Behavioral data are considered but the main focus lies on neuroscientific methods like event-related potentials ( ERPs ) and functional magnetic resonance imaging ( fMRI ) This is the first r and omized , controlled study comparing the cognitive effects of transcranial laser stimulation and acute aerobic exercise on the same cognitive tasks . We examined whether transcranial infrared laser stimulation of the prefrontal cortex , acute high-intensity aerobic exercise , or the combination may enhance performance in sustained attention and working memory tasks . Sixty healthy young adults were r and omly assigned to one of the following four treatments : ( 1 ) low-level laser therapy ( LLLT ) with infrared laser to two forehead sites while seated ( total 8 min , 1064 nm continuous wave , 250 mW/cm2 , 60 J/cm2 per site of 13.6 cm2 ) ; ( 2 ) acute exercise ( EX ) of high-intensity ( total 20 min , with 10-min treadmill running at 85–90 % VO2max ) ; ( 3 ) combined treatment ( LLLT + EX ) ; or ( 4 ) sham control ( CON ) . Participants were tested for prefrontal measures of sustained attention with the psychomotor vigilance task ( PVT ) and working memory with the delayed match-to- sample task ( DMS ) before and after the treatments . As compared to CON , both LLLT and EX reduced reaction time in the PVT [ F(1.56 ) = 4.134 , p = 0.01 , η2 = 0.181 ] and increased the number of correct responses in the DMS [ F(1.56 ) = 4.690 , p = 0.005 , η2 = 0.201 ] , demonstrating a significant enhancing effect of LLLT and EX on cognitive performance . LLLT + EX effects were similar but showed no significantly greater improvement on PVT and DMS than LLLT or EX alone . The transcranial infrared laser stimulation and acute aerobic exercise treatments were similarly effective for cognitive enhancement , suggesting that they augment prefrontal cognitive functions similarly OBJECTIVE To simultaneously examine the effects of acute exercise intensity and free-living physical activity and sedentary behavior on cognitive function in young , healthy adults . PATIENTS AND METHODS Using a counterbalanced , crossover , r and omized controlled design , 87 young adults ( mean age , 21.4 years ) completed various cognitive assessment s with and without an acute bout of exercise preceding the assessment . Participants were r and omized into 1 of 4 groups to complete a 30-minute bout of acute exercise : control ( no exercise ) , light intensity ( 40%-50 % of predicted maximum heart rate [ HR(max ) ] ) , moderate intensity ( 51%-70 % of predicted HR(max ) ) , or vigorous intensity ( 71%-85 % of predicted HR(max ) ) . Subjectively and objective ly determined ( accelerometry ) physical activity and sedentary behavior were assessed to examine the association between these free-living behaviors and cognitive function . The study duration was August 26 , 2013 , to September 11 , 2014 . RESULTS Concentration-related cognition ( mean ± SD Feature Match test score ) was significantly higher after a 30-minute acute bout of moderate-intensity exercise ( 145.1±26.9 ) compared with cognitive assessment without exercise ( 121.3±19.2 ; P=.004 ) . Furthermore , question naire-determined sedentary behavior was inversely associated with visual attention and task switching ( Trail Making Test A score ) ( β=-0.23 ; P=.04 ) . Last , estimated cardiorespiratory fitness ( volume of maximum oxygen consumption ) was positively associated with reasoning-related cognitive function ( Odd One Out test score ) ( β=0.49 ; P=.05 ) ; when adding metabolic equivalent of task minutes per week to this model , the results were not significant ( β=0.47 ; P=.07 ) . CONCLUSION These findings provide some support for acute moderate-intensity exercise , sedentary behavior , and cardiorespiratory fitness being associated with executive functioning-related cognitive function in young , healthy adults In this study , we tested the effect of acute exercise on long-term memory , specifically the timing of exercise relative to the memory challenge . We assessed memory via paragraph recall , in which participants listened to two paragraphs ( exposure ) and recounted them following a 35-min delay . Participants ( n = 48 ) were r and omly assigned to one of three groups : exercise prior to exposure , exercise after exposure , or no-exercise . Exercise consisted of 30 min on a cycle ergometer , including 20 min at moderate intensity . Only the exercise-prior group recalled significantly more than the control group ( p < .05 ) . Differences among the exercise groups failed to reach significance ( p = .09 ) . Results indicated that acute exercise positively influenced recall and that exercise timing relative to memory task may have an impact on this effect There is a paucity of methods for improving the affective experience of exercise . We tested a novel method based on discoveries about the relation between exercise intensity and pleasure , and lessons from behavioral economics . We examined the effect of reversing the slope of pleasure during exercise from negative to positive on pleasure and enjoyment , remembered pleasure , and forecasted pleasure . Forty-six adults were r and omly assigned to a 15-min bout of recumbent cycling of either increasing intensity ( 0 - 120 % of watts corresponding to the ventilatory threshold ) or decreasing intensity ( 120 - 0 % ) . Ramping intensity down , thereby eliciting a positive slope of pleasure during exercise , improved postexercise pleasure and enjoyment , Output:	Conclusion : Acute and chronic exercise appears to play a pronounced effect on memory function among young to middle-aged adults .
MS21640	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The aim of this clinical study was to evaluate the association of locally delivered doxycycline ( 10 % ) with scaling and root planing in the periodontal treatment of smokers . METHODS Forty-three patients with chronic periodontitis and a minimum of four pockets ( > or = 5 mm ) on anterior teeth that bled on probing were selected . Patients were r and omly assigned to scaling and root planing ( SRP ) or scaling and root planing followed by local application of doxycycline ( SRP-D ) . Plaque , bleeding on probing , gingival recession , relative attachment level ( RAL ) , and probing depth ( PD ) were recorded at baseline , 45 days , and 3 and 6 months . Differences between baseline and each period were considered for analysis . RESULTS At 6 months , no difference was found between groups regarding plaque , bleeding reduction , gingival recession or PD ( P > 0.05 ) . However , RAL gain was greater for SRP-D ( 1.63 + /- 0.93 mm ) than for SRP ( 1.04 + /- 0.71 mm ) ( P = 0.025 ) . In addition , deep pockets ( > or = 7 mm ) showed a significant reduction ( 3.78 + /- 1.41 versus 2.60 + /- 1.28 mm , P = 0.039 ) and RAL gain ( 2.54 + /- 1.27 mm versus 1.29 + /- 0.95 mm , P = 0.01 ) when doxycycline was applied . The proportion of sites showing RAL gain of 1 to 2 mm was 36.8 % versus 21.7 % for SRP-D and SRP , respectively ( P = 0.01 ) . CONCLUSION The use of locally delivered doxycycline may constitute an important adjunct for the treatment of severe periodontal disease in smokers BACKGROUND Although scaling and root planing are considered the therapeutic st and ard for periodontitis , weakly responding sites often occur . To improve treatment outcome , several chemomechanical treatment concepts have been developed . Recently , the clinical surplus value of a highly concentrated chlorhexidine varnish has been shown when used as an adjunct to sequential scaling and root planing . The aim of this study was to explore the clinical effects of a treatment strategy for chronic periodontitis based on a combination of same-day full-mouth root planing and subgingival chlorhexidine varnish administration . METHODS A r and omized , controlled , single-blind , parallel trial was conducted on 12 chronic periodontitis patients . The control group received oral hygiene instructions and same-day full-mouth root planing . The test group received the same instructions and treatment ; however , all pockets were additionally disinfected using a chlorhexidine varnish . Clinical response parameters were recorded at baseline and subsequently after 1 and 3 months . RESULTS Both treatment strategies showed significant reductions in probing depth at both follow-up visits in comparison with baseline levels ( P < or=0.029 ) . Yet , at 3 months , initially diseased sites of the test group showed significant additional pocket reductions between 0.70 and 1.37 mm ( P < or=0.021 ) . Furthermore , a significant additive clinical attachment gain of 1.17 mm ( P = 0.049 ) for initially deep pockets ( > or=7 mm ) was found favoring the test group . CONCLUSION These preliminary findings suggest that the outcome of same-day full-mouth root planing may benefit from the subgingival administration of a highly concentrated chlorhexidine varnish The present study was performed to assess and compare the clinical healing and the microbiological findings following local application of metronidazole or tetracycline to augment subgingival scaling in previously untreated adult periodontitis sites . Eighteen patients with moderate to severe adult periodontitis at single-rooted teeth were selected . In each patient , 3 interproximal sites having comparable root anatomy , probing depth > or = 5 mm and bleeding on probing were r and omly assigned to 1 of 3 treatment groups : 1 ) two sessions of subgingival scaling and root planing ; 2 ) similar to 1 , with each treatment supplemented with a 25 % metronidazole sustained release gel ; 3 ) similar to 1 with each treatment supplemented with a 3 % tetracycline ointment . The treatments were performed by 1 operator and the clinical variables probing depth , attachment level , and bleeding on probing were evaluated at baseline , 3 months and 6 months by a second blinded examiner . The microbiological findings were evaluated using a commercial test kit . The average probing depth reduction for the 3 groups at 6 months was 1.5 mm and the average gain of clinical attachment was 0.8 mm . There were no significant differences between the effects following topical application of the metronidazole gel or the tetracycline ointment . Scaling and root planing alone appeared as effective as the drug augmented regimens , although there was a weak but non-significant tendency for better results in sites treated with the antibiotic drugs . Actinobacillus actinomycetemcomitans was generally not detected ; Prevotella intermedia was not significantly reduced , while Porphyromonas gingivalis was significantly reduced in all treatment groups . It was concluded that the augmentative effect of the metronidazole gel and the tetracycline ointment was comparable but small compared to scaling and root planing alone . The clinical importance of such small augmentation effects should be further evaluated BACKGROUND Currently , several local antimicrobial delivery systems are available to periodontists . The aim of this 6-month follow-up parallel study was to evaluate the efficacy of three commercially available local delivery systems as adjuncts to scaling and root planing in the treatment of sites with persistent periodontal lesions . METHODS Seventy-nine patients with 4 pockets > or = 5 mm and bleeding on probing and /or suppuration were r and omized into 4 treatment groups which included : scaling and root planing alone ( S ) ( 20 patients ) , or in conjunction with the application of 25 % tetracycline fibers ( S+Tet ) ( 19 patients ) , or 2 % minocycline gel ( S+Min ) ( 21 patients ) , or 25 % metronidazole gel ( S+Met ) ( 19 patients ) . Clinical measurements were taken at baseline , 6 weeks , 3 months , and 6 months after antimicrobial application . Treatments were applied using the distributors ' recommended protocol s. RESULTS All 4 therapies result ed in significant improvements from baseline in probing depth , attachment level , bleeding on probing , and the Modified Gingival Index ( MGI ) scores . The improvements in clinical parameters were greater in all 3 adjunctive treatment groups than scaling and root planing alone . The mean probing depth reductions at 6 months were : scaling + tetracycline = 1.38 mm ; scaling + metronidazole = 0.93 mm ; scaling + minocycline = 1.10 mm ; and scaling alone = 0.71 mm . The probing depth reduction at all time points was significantly greater in the scaling plus tetracycline fiber group than the scaling and root planing alone group ( P<0.01 ) . There was also a significant improvement for scaling plus tetracycline fiber application over scaling and metronidazole at both 6 weeks and 3 months , although this did not remain significant at the 6-month visit . While the frequency of sites with suppuration was markedly reduced following all antimicrobial treatments , the most effective reductions were seen in the scaling plus tetracycline fiber group , followed by the minocycline group . CONCLUSIONS Although all 3 locally applied antimicrobial systems seem to offer some benefit over scaling and root planing alone , a treatment regimen of scaling and root planing plus tetracycline fiber placement gave the greatest reduction in probing depth over the 6 months after treatment BACKGROUND Several antibacterial agents have been studied as a means to produce bactericidal or bacteriostatic activity as an adjunct to mechanical treatment of periodontal disease . The primary purpose of this study was to evaluate the efficacy of tetracycline strips administered singly or in multiples in conjunction with root planing , versus root planing alone , or to an untreated control . Secondary purpose s were to compare gingival crevicular fluid ( GCF ) volume and GCF concentrations of tetracycline in pockets treated with strips ; to evaluate strip insertion time ; and to compare ease of placement for single or multiple strips . METHODS Using a 4-quadrant design , 4 test teeth in 24 patients were treated with either root planing and single strip application ; root planing and multiple strip application ; root planing alone ; or an untreated control . RESULTS Single and multiple strip placement result ed in a significant reduction in probing depth ( P = 0.033 ) compared to root planing and untreated groups . The multiple strip group significantly decreased bleeding on probing ( P = 0.05 ) compared to all other treatment groups . There was no treatment effect on GCF ; however , there was a significant reduction in the GCF volume over time ( P = 0.001 ) . The time required for placement was , on average , 1.9 minutes for single strips and 3.25 minutes for multiple strips . CONCLUSIONS Our data suggest that multiple strips are superior to a single strip in reducing bleeding on probing , and that local delivery of tetracycline is superior to root planing alone in reducing probing depth AIM To determine whether adjunctive metronidazole therapy would compensate for the poorer treatment response to scaling and root planing reported in smokers . METHOD A single-blind , r and omised clinical trial of 28 smokers and 56 non-smokers , stratified for periodontitis disease severity and r and omly allocated to 3 treatment groups : ( 1 ) Scaling and root planing using an ultrasonic scaler with local anaesthesia ( SRP ) , ( 2 ) SRP+ metronidazole tabs 200 mg tds for 7 days , ( 3 ) SRP + 2 subgingival applications of 25 % metronidazole gel . Probing depths ( PD ) and attachment levels ( AL ) were recorded with a Florida probe at baseline , 2 months and 6 months post treatment by a single examiner who was unaware of the treatment modality . Results were analysed for all sites with baseline probing depths equal to or greater than Florida probe recordings of 4.6 mm using analysis of variance . RESULTS Reductions in probing depth at 6 months were significantly less ( p < 0.001 ) in the smokers ( mean 1.23 mm , 95 % confidence intervals = 1.05 to 1.40 mm ) than in the non-smokers ( 1.92 , 1.75 to 2.09 mm ) . Attachment level gains were approximately 0.55 mm and there was no statistically significant difference between smokers and non-smokers . There were no differences in any clinical measure in response to the three treatment regimens at 2 or 6 months for either smokers or non-smokers . A reduction in the proportion of spirochaetes was observed at 6 months which was less in smokers than in non-smokers ( p = 0.034 ) . Multiple linear regression analysis on probing depth at 6 months demonstrated that smoking was a significant explanatory factor ( p < 0.001 ) for poor treatment outcome , whilst the presence or absence of adjunctive metronidazole was not ( p = 0.620 ) . CONCLUSION This study confirms that smokers have a poorer treatment response to SRP , regardless of the application of either systemic or locally applied adjunctive metronidazole BACKGROUND Tetracyclines have been extensively used as adjunctives to conventional periodontal therapy . Emergence of resistant strains , however , has been reported . This study evaluated longitudinally the tetracycline resistance patterns of the subgingival microbiota of periodontitis subjects treated with systemic or local tetracycline therapy+scaling and root planing ( SRP ) . METHODS Thirty chronic periodontitis patients were r and omly assigned to three groups : SRP+500 mg of systemic tetracycline twice/day for 14 days ; SRP alone and SRP+tetracycline fibers ( Actsite ) at four selected sites for 10 days . Subgingival plaque sample s were obtained from four sites with probing pocket depths ( PPD ) > or = 6 mm in each patient at baseline , 1 week , 3 , 6 and 12 months post-therapy . Sample s were dispersed and diluted in pre-reduced anaerobically sterilized Ringer 's solution , plated on Trypticase Soy Agar (TSA)+5 % blood with or without 4 microg/ml of tetracycline and incubated anaerobically for 10 days . The percentage of resistant microorganisms were determined and the isolates identified by DNA probes and the checkerboard method . Significance of differences among and within groups over time was sought using the Kruskal-Wallis and Friedman tests , respectively . RESULTS The percentage of resistant microorganisms increased significantly at 1 week in the tetracycline groups , but dropped to baseline levels over time . The SRP+Actsite group presented the lowest proportions of resistant species at 6 and 12 months . No significant changes were observed in the SRP group . The predominant tetracycline-resistant species included Streptococcus spp . , Veillonela parvula , Peptostreptococcus micros , Prevotella intermedia , Gemella morbillorum and Actinobacillus actinomycetemcomitans ( Aa ) . A high percentage of sites with resistant Aa , Porphyromonas gingivalis and Tanerella forsythensis was observed in all groups at baseline . However , T. forsythensis was not detected in any group and P. gingival Output:	The local application of chlorhexidine and metronidazole showed a minimal effect when compared with placebo ( WMD between 0.1 and 0.4 mm ) . The scientific evidence supports the adjunctive use of local antimicrobials to debridement in deep or recurrent periodontal sites , mostly when using vehicles with proven sustained release of the antimicrobial
MS21641	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The authors compared the efficacy of bilateral balanced and canine guidance ( occlusal ) splints in the treatment of temporom and ibular joint ( TMJ ) pain in subjects who experienced joint clicking with a nonoccluding splint in a double-blind , controlled r and omized clinical trial . METHODS The authors r and omly assigned 57 people with signs of disk displacement and TMJ pain into three groups according to the type of splint : bilateral balanced , canine guidance and nonoccluding . The authors followed the groups for six months using analysis of a visual analog scale ( VAS ) , palpation of the TMJ and masticatory muscles , m and ibular movements and joint sounds . They used repeated analysis of variance and a chi(2 ) test to test the hypothesis . RESULTS The type of guidance used did not influence the pain reduction , yet both occlusal splints were superior to the nonoccluding splint , on the basis of the VAS . Despite similar outcomes in relation to opening , left lateral and protrusive movements , TMJ and muscle pain on palpation , subjects who used the occlusal splints had improved clinical outcomes . The frequency of joint noises decreased over time , with no significant differences among groups . Subjects in the groups using the occlusal splints reported more comfort . CONCLUSION The type of lateral guidance did not influence the subjects ' improvement . All of the subjects had a general improvement on the VAS , though subjects in the occlusal splint groups had better results that did subjects in the nonoccluding splint group Sixty-three patients with an arthrographic diagnosis of disk displacement with reduction were r and omly assigned to three treatment groups : ( I ) onlays to maintain disk repositioning , ( II ) flat occlusal splint , or ( III ) untreated controls . Guidance for construction of the disk-repositioning onlays was established during arthrography to obtain a recaptured disk position relative to the condyle . The onlays were cemented to the teeth and maintained the new intercuspal position anteriorly and inferiorly . The flat occlusal splint was used at night only and was adjusted to maintain a maximal occlusal contact in centric relation and centric occlusion . Clinical examinations were performed before and after 6 months of treatment . The disk-repositioning onlays improved joint function and reduced joint and muscle pain when compared with the flat occlusal splint and with nontreatment . The signs and symptoms in the flat occlusal splint group were no different from those in the control group . It is concluded that disk-repositioning onlays are effective in reducing pain and dysfunction associated with disk displacement with reduction in patients in whom the disk can be maintained in a normal relationship to the condyle with the aid of such onlays . The symptoms , however , returned when the onlays were removed after 6 months ; this raises the question of whether a permanent change in the intercuspal position is necessary for long-term success Forty-five individuals with long-st and ing facial pain or headache of muscular origin were r and omly allocated into three groups . The first group was treated with acupuncture , the second group received an occlusal splint , and the third group served as controls . Both acupuncture and occlusal splint therapy significantly reduced subjective symptoms and clinical signs from the stomatognathic system . No differences between these two groups were found with regard to treatment effects . It is concluded that acupuncture is an alternative method to conventional stomatognathic treatment for individuals with craniom and ibular disorders of muscular origin OBJECTIVE To test the reliability and validity of specific instructions to classify blinding , when unclearly reported in r and omized trials , as " probably done " or " probably not done . " STUDY DESIGN AND SETTING We assessed blinding of patients , health care providers , data collectors , outcome adjudicators , and data analysts in 233 r and omized trials in duplicate and independently using detailed instructions . The response options were " definitely yes , " " probably yes , " " probably no , " and " definitely no. " We contacted authors for data verification ( 46 % response ) . For each of the five questions , we assessed reliability by calculating the agreement between the two review ers and validity by calculating the agreement between review ers ' consensus and verified data . RESULTS The percentage with unclear blinding status varied between 48.5 % ( patients ) and 84.1 % ( data analysts ) . Reliability was moderate for blinding of outcome adjudicators ( κ=0.52 ) and data analysts ( κ=0.42 ) and substantial for blinding of patients ( κ=0.71 ) , providers ( κ=0.68 ) , and data collectors ( κ=0.65 ) . The raw agreement between the consensus record and the author-verified record varied from 84.1 % ( blinding of data analysts ) to 100 % ( blinding of health care providers ) . CONCLUSION With the possible exception of blinding of data analysts , use of " probably yes " and " probably no " instead of " unclear " may enhance the assessment of blinding in trials To assess the differential efficacy of two commonly used treatments for temporom and ibular disorders ( TMD ) , intraoral appliances ( IAs ) and biofeedback ( BF ) , separately and in combination , two studies were conducted . The first study directly compared IA treatment , a combination of biofeedback and stress management ( BF/SM ) , and a waiting list control group in a sample of 80 TMD patients . Both treatments were determined to be equally credible to patients , ruling out this potential threat to the validity of the results obtained . The results demonstrated that the IA treatment was more effective than the BF/SM treatment in reducing pain after treatment , but at a 6-month follow-up the IA group significantly relapsed , especially in depression , whereas the BF/SM maintained improvements on both pain and depression and continued to improve . The second study examined the combination of IA and BF/SM in a sample of 30 TMD patients . The results of this study demonstrated that the combined treatment approach was more effective than either of the single treatments alone , particularly in pain reduction , at the 6-month follow-up . These results support the importance of using both dental and psychologic treatments to successfully treat TMD patients if treatment gains are to be maintained BACKGROUND Treatment recommendations for patients with painful temporom and ibular disorders ( TMDs ) range from conservative treatments such as physiotherapy to aggressive and irreversible treatments such as restorative reconstruction and joint surgery . METHODS The authors r and omized 200 subjects diagnosed with TMD into three groups : usual conservative , dentist-prescribed self-care treatment without any intraoral splint appliance ( UT ) ; UT plus a conventional flat-plane hard acrylic splint ( HS ) ; and UT plus a soft vinyl ( a low-cost athletic mouth guard ) splint ( SS ) . Subjects completed question naires and clinical examinations at three , six and 12 months . RESULTS The authors observed no significant differences among the groups in TMD-related pain levels or other common signs and symptoms of TMD at baseline ( BL ) or at any follow-up . The changes from BL were comparable for all three groups . The authors did not note any significant differences at any follow-up for compliance with study protocol s or for occurrences of adverse effects from either splint type . For HS versus SS , there were significant differences in rates of splint use , but these differences were not accompanied by differences in either self-reported symptoms or in clinical findings . CONCLUSIONS All patients improved over time , and traditional splint therapy offered no benefit over the SS splint therapy . Neither splint therapy provided a greater benefit than did self-care treatment without splint therapy . CLINICAL IMPLICATION S These findings suggest that clinicians who treat patients with TMD should consider prescribing low-cost nonsplint self-care therapy for most patients One hundred and ten patients , 23 males and 87 females , participated in a comparative study of the effect of acupuncture and occlusal splint therapy . All the patients exhibited signs and symptoms of craniom and ibular disorders ( CMD ) and had had pain for more than six months . The participants were r and omly assigned to three groups ; acupuncture treatment , occlusal splint therapy or control . The patients were evaluated before and immediately after treatment/control time . Ten different subjective and /or clinical assessment variables were used in the evaluation of the treatment effects . Both acupuncture and occlusal splint therapy reduced the symptoms as compared with the control group in which the symptoms remained essentially unchanged . In this short-term study , acupuncture gave better subjective results ( p < 0.001 ) than the occlusal splint therapy A r and om sample of U.S. dentists was surveyed with a mailed question naire to determine the number of splints that they fabricated over the preceding year for bruxers , patients with myofascial pain-dysfunction syndrome and patients with TM joint pain . The results indicate that a significant number of dentists treat these disorders with dental splints . Estimates are provided for the dental profession 's yearly splint output for each disorder Objectives Studies have suggested overlaps between various chronic pain conditions and painful temporom and ibular disorders ( TMDs ) . The objective of this pilot study was to assess the effectiveness of occlusal splint ( OS ) therapy on self-reported measures of pain in patients with chronic complex regional pain syndrome ( CRPS ) as compared with a nontreatment group . Methods The design was a prospect i ve r and omized controlled clinical trial . Twenty patients with CRPS were r and omly assigned to either the OS or control group . The patients in the OS group were asked to use the OS at nighttime and for 3 hours during daytime for a total of 7 weeks ; the control group had no stomatognathic intervention . The primary outcome was self-reported assessment of CRPS-related pain on numerical rating scales . Secondary outcome measures were the Temporom and ibular Index ( TMI ) , and the Short Form 36 Health Survey ( SF-36 ) . Results All patients had TMD signs and symptoms , but OS had no effect on CRPS-related pain on the numerical rating scale ( P>0.100 ) . The changes in the TMI scores over time were 16.6%±24.6 % ( improvement ) in the OS group and −21.3%±25.9 % ( impairment ) in the control group that was significant ( P=0.004 ) . There were no differences in the changes of SF-36 scores between groups ( P=0.636 ) . Discussion The use of OS for 7 weeks has no impact on CRPS-related pain but improved signs and symptoms of TMD pain . Future studies should include an active control group and evaluate if long-term changes in measures of oral health impact general health in CRPS-related pain Thirty subjects seeking treatment for masticatory muscle pain at a university-based TMJ clinic were r and omly assigned to soft-splint , palliative-treatment , and no-treatment groups . After 4 to 11 weeks of treatment , subjects were evaluated for changes from their baseline levels of symptoms , maximum pain-free opening , pain thresholds measured by a pressure algometer , and occlusal contacts . With the use of the multivariate analysis of variance and analysis of covariance , the results suggest that the soft-splint group had statistically significant improvement ( P < .01 ) , the palliative-treatment group had improvement that was not statistically significant , and the no-treatment group had a slight aggravation of symptoms . The soft-splint group had fewer occlusal contact changes assessed with shimstock compared to the palliative-treatment and no-treatment groups . The findings of this study suggest that the soft splint is an effective short-term treatment for reducing the signs and symptoms of masticatory muscle pain in patients , and the soft splint does not cause occlusal changes Two occlusal splints , the full-arch stabilization splint and the anterior midline point stop ( AMPS ) device , were evaluated for their efficiency in relieving myogenous temporom and ibular disorders ( TMD ) . One hundred and fourteen patients with myogenous TMD were distributed into 3 groups . The first group was treated with the AMPS device , the second with the stabilization splint , and the third group was the control group . Pain intensity was scored using the visual analogue scale before treatment and 1 month and 3 months after treatment . Statistical Package for the Social Sciences ( SPSS , Chicago , Ill ) and multiple comparisons tests were used to compare results before and after treatment and to compare the groups . The use of AMPS device in the first group result ed in a significant improvement after 1 month and 3 months ( P < or = .001 ) and showed a 56.66 % pain reduction . A significant improvement was also noticed in the second group ( P = .001 ) with a 47.71 % pain reduction . Although pain reduction percentage appeared more in the first group , this was not statistically significant . There was a highly significant difference between groups treated with both kinds of splints and the control group . It was concluded that both types of occlusal splints are beneficial to patients with myogenous TMD The purpose of this study was to examine the psychometric properties of the Quality of Life Index ( QLI ) ( Ferrans & Powers , 1985a ) . The sample consisted of 349 patients selected r and omly from the adult , in-unit hemodialysis patient population of Illinois . Factor analysis was used to examine the underlying factor structure . A four-factors solution best fit the data , indicating that there were four dimensions underlying the QLI : health and functioning , socioeconomic , psychological/spiritual , and family . Factor analysis of the four primary factors revealed one higher order factor , representing quality of life . Construct validity also was supported by the contrasted groups approach . As predicted , it was found that those who had higher incomes had significantly higher quality of life scores on the social and economic subscale . Support for convergent validity was provided by a strong correlation ( r = .77 ) between scores from the QLI and an assessment of life satisfaction . Findings supported the internal consistency reliability of the entire QLI ( alpha = .93 ) and the four subscales ( alphas = .87 , .82 , .90 , .77 ) A flat occlusal splint has been extensively used in the treatment of patients with temporom and i Output:	Low to very low quality of evidence showed no significant differences between the splint therapy and control groups in terms of quality of life or depression . None of the trial reports described effect on function .
MS21642	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : To develop and vali date a comprehensive ex vivo training curriculum for laparoscopic colorectal surgery . Background : Simulators have been shown to be viable systems for teaching technical skills outside the operating room ; however , integration of simulation training into comprehensive curricula remains a major challenge in modern surgical education . Currently , no curricula have been described or vali date d for advanced laparoscopic procedures . Methods : This prospect i ve , single-blinded r and omized controlled trial allocated 25 surgical residents to receive either conventional residency training or a comprehensive training curriculum for laparoscopic colorectal surgery . The curriculum consisted of proficiency-based psychomotor training on a virtual reality simulator , cognitive training , and participation in a cadaver lab . The primary outcome measure in this study was surgical performance in the operating room . All participants performed a laparoscopic right colectomy , which was video recorded and assessed using 2 previously vali date d assessment tools . Secondary outcome measures were knowledge relating to the execution of the procedure , assessed with a multiple-choice test , and technical performance on the simulator . Results : Curricular-trained residents demonstrated superior performance in the operating room compared with conventionally trained residents ( global score 16.0 [ 14.5–18.0 ] versus 8.0 [ 6.0–14.5 ] , P = 0.030 ; number of operative steps performed 16.0 [ 12.5–17.5 ] versus 8.0 [ 6.0–14.5 ] , P = 0.021 ; procedure-specific score 71.1 [ 54.4–81.6 ] versus 51.1 [ 36.7–74.4 ] , P = 0.122 ) . Curricular-trained residents scored higher on the multiple-choice test ( 10 [ 9–11 ] versus 7.5 [ 5.3–7.5 ] , P = 0.047 ) , and outperformed conventionally trained residents in 7 of 8 tasks on the simulator . Conclusions : Participation in a comprehensive ex vivo training curriculum for laparoscopic colorectal surgery results in improved technical knowledge and improved performance in the operating room compared with conventional residency training . Reg . ID#NCT 01371136 BACKGROUND The efficacy of laparoscopy simulators remains controversial . METHODS This was a comparative prospect i ve study that evaluated the impact of simulator training on technical competence during a real surgical procedure . Residents were divided into 3 groups : the Mcgill Inanimate System for Training and Evaluation of Laparoscopic Skills ( MISTELS ) group , training on a simple simulator ; LAP Mentor group , training on a virtual simulator ; and control group . An initial evaluation was made by a vali date d score during a laparoscopic cholecystectomy . Each resident was then trained for 1 month . A second evaluation was then performed . RESULTS Before/after scores were significantly improved in the MISTELS ( P = .042 ) and LAP Mentor ( P = .026 ) groups . It was not the case in the control group . There was a better progression in the MISTELS ( P = .026 ) and LAP Mentor ( P = .007 ) groups than in the control group . There was no significant difference between the MISTELS and LAP Mentor groups . CONCLUSIONS Simulator training provides a more rapid acquisition of competence in surgical technique BACKGROUND Developing technical skill is essential to surgical training , but using the operating room for basic skill acquisition may be inefficient and expensive , especially for laparoscopic operations . This study determines if laparoscopic skills training using simulated tasks on a video-trainer improves the operative performance of surgery residents . STUDY DESIGN Second- and third-year residents ( n= 27 ) were prospect ively r and omized to receive formal laparoscopic skills training or to a control group . At baseline , residents had a vali date d global assessment of their ability to perform a laparoscopic cholecystectomy based on direct observation by three evaluators who were blinded to the residents ' r and omization status . Residents were also tested on five st and ardized video-trainer tasks . The training group practice d the video-trainer tasks as a group for 30 minutes daily for 10 days . The control group received no formal training . All residents repeated the video-trainer test and underwent a second global assessment by the same three blinded evaluators at the end of the 1-month rotation . Within-person improvement was determined ; improvement was adjusted for differences in baseline performance . RESULTS Five residents were unable to participate because of scheduling problems ; 9 residents in the training group and 13 residents in the control group completed the study . Baseline laparoscopic experience , video-trainer scores , and global assessment s were not significantly different between the two groups . The training group on average practice d the video-trainer tasks 138 times ( range 94 to 171 times ) ; the control group did not practice any task . The trained group achieved significantly greater adjusted improvement in video-trainer scores ( five of five tasks ) and global assessment s ( four of eight criteria ) over the course of the four-week curriculum , compared with controls . CONCLUSIONS Intense training improves video-eye-h and skills and translates into improved operative performance for junior surgery residents . Surgical curricula should contain laparoscopic skills training Objective : To assess the McGill Inanimate System for Training and Evaluation of Laparoscopic Skills ( MISTELS ) physical laparoscopic simulator for construct and predictive validity and for its educational utility . Summary Background Data : MISTELS is the physical simulator incorporated by the Society of American Gastrointestinal and Endoscopic Surgeons ( SAGES ) in their Fundamentals of Laparoscopic Surgery ( FLS ) program . MISTELS ’ metrics have been shown to have high interrater and test-retest reliability and to correlate with skill in animal surgery . Methods : Over 200 surgeons and trainees from 5 countries were assessed using MISTELS in a series of experiments to assess the validity of the system and to evaluate whether practicing MISTELS basic skills ( transferring ) would result in skill acquisition transferable to complex laparoscopic tasks ( suturing ) . Results : Face validity was confirmed through question ing 44 experienced laparoscopic surgeons using global rating scales . MISTELS scores increased progressively with increasing laparoscopic experience ( n = 215 , P < 0.0001 ) , and residents followed over time improved their scores ( n = 24 , P < 0.0001 ) , evidence of construct validity . Results in the host institution did not differ from 5 beta sites ( n = 215 , external validity ) . MISTELS scores correlated with a highly reliable vali date d intraoperative rating of technical skill during laparoscopic cholecystectomy ( n = 19 , r = 0.81 , P < 0.0004 ; concurrent validity ) . Novice laparoscopists were r and omized to practice /no practice of the transfer drill for 4 weeks . Improvement in intracorporeal suturing skill was significantly related to practice but not to baseline ability , career goals , or gender ( P < 0.001 ) . Conclusion : MISTELS is a practical and inexpensive inanimate system developed to teach and measure technical skills in laparoscopy . This system is reliable , valid , and a useful educational tool This study examined the impact of virtual reality ( VR ) surgical simulation on improvement of psychomotor skills relevant to the performance of laparoscopic cholecystectomy OBJECTIVE ( S ) Patient-specific simulated rehearsal ( PsR ) is a technological advance within the domain of endovascular virtual reality ( VR ) simulation . It allows incorporation of patient-specific computed tomography Digital Imaging and Communications in Medicine ( CT DICOM ) data into the simulation and subsequent rehearsal of real patient cases . This study aim ed to evaluate whether a part-task rehearsal ( PTr ) of a carotid artery stenting procedure ( CAS ) on a VR simulator is as effective as a full-task ( FTr ) preoperative run through . METHODS Medical trainees were trained in the CAS procedure and r and omised to a PTr or FTr of a challenging CAS case ( Type-II arch ) . PTr consisted of 30 min of repeated catheterisations of the common carotid artery ( CCA ) . Thereafter , both groups performed the CAS procedure in a fully functional simulated operating suite ( SOS ) with an interventional team . Technical performances were assessed using simulator-based metrics and expert ratings . Other aspects of performance were assessed using the Non-Technical Skills for Surgeons ( NOTSS ) scoring . RESULTS Twenty trainees were evenly r and omised to either PTr or FTr . No differences in performance were seen except for the total time the embolic protection device ( EPD ) was deployed ( 9.4 min for the PT vs. 8.1 min for the FT , p = 0.02 ) . Total time ( 26.3 vs. 25.5 min , p = 0.94 ) , fluoroscopy time ( 15.8 vs. 14.4 min , p = 0.68 ) , number of roadmaps ( 10.5 vs. 11.0 , p = 0.54 ) , amount of contrast ( 53.5 vs. 58.0 ml , p = 0.33 ) , time to deploy the EPD ( 0.9 vs. 0.8 min , p = 0.31 ) and time to catheterise the CCA ( 9.2 vs. 8.9 min , p = 0.94 ) were similar . Qualitative performances as measured by expert ratings ( score 24 vs. 24 , p = 0.49 ) and NOTSS ( p > 0.05 for all categories ) were also comparable . CONCLUSIONS Part- and full-task rehearsals are equally effective with respect to the operative performance of a simulated CAS intervention . This finding makes a patient-specific rehearsal more efficient and may increase the feasibility of implementation of this technology into medical practice Objectives : The development of a structured virtual reality ( VR ) training curriculum for colonoscopy using high-fidelity simulation . Background : Colonoscopy requires detailed knowledge and technical skill . Changes to working practice s in recent times have reduced the availability of traditional training opportunities . Much might , therefore , be achieved by applying novel technologies such as VR simulation to colonoscopy . Scientifically developed device-specific curricula aim to maximize the yield of laboratory-based training by focusing on vali date d modules and linking progression to the attainment of benchmarked proficiency criteria . Methods : Fifty participants comprised of 30 novices ( < 10 colonoscopies ) , 10 intermediates ( 100 to 500 colonoscopies ) , and 10 experienced ( > 500 colonoscopies ) colonoscopists were recruited to participate . Surrogates of proficiency , such as number of procedures undertaken , determined prospect i ve allocation to 1 of 3 groups ( novice , intermediate , and experienced ) . Construct validity and learning value ( comparison between groups and within groups respectively ) for each task and metric on the chosen simulator model determined suitability for inclusion in the curriculum . Results : Eight tasks in possession of construct validity and significant learning curves were included in the curriculum : 3 abstract tasks , 4 part-procedural tasks , and 1 procedural task . The whole-procedure task was valid for 11 metrics including the following : “ time taken to complete the task ” ( 1238 , 343 , and 293 s ; P < 0.001 ) and “ insertion length with embedded tip ” ( 23.8 , 3.6 , and 4.9 cm ; P = 0.005 ) . Learning curves consistently plateaued at or beyond the ninth attempt . Valid metrics were used to define benchmarks , derived from the performance of the experienced cohort , for each included task . Conclusions : A comprehensive , stratified , benchmarked , whole-procedure curriculum has been developed for a modern high-fidelity VR colonoscopy simulator PURPOSE : The aim of this study was to compare skills sets during a h and -assisted and straight laparoscopic colectomy on an augmented reality simulator . METHODS : Twenty-nine surgeons , assigned r and omly in 2 groups , performed laparoscopic sigmoid colectomies on a simulator : group A ( n = 15 ) performed h and -assisted then straight procedures ; group B ( n = 14 ) performed straight then h and -assisted procedures . Groups were compared according to prior laparoscopic colorectal experience , performance ( time , instrument path length , and instrument velocity changes ) , technical skills , and operative error . RESULTS : Prior laparoscopic colorectal experience was similar in both groups . Both groups had better performances with the h and -assisted approach , although technical skill scores were similar between approaches . The error rate was higher with the h and -assisted approach in group A , but similar between both approaches in group B. CONCLUSIONS : These data define the metrics of performance for h and -assisted and straight laparoscopic colectomy on an augmented reality simulator . The improved scores with the h and -assisted approach suggest that with this simulator a h and -assisted model may be technically easier to perform , although it is associated with increased intraoperative errors Background Minimally invasive surgery in small children and infants requires special skills and training . This experimental study compares the efficiency of an in vitro pelvic trainer ( PT ) and an a in vivo animal model ( AM ) . Methods For this study , 12 residents were prospect ively r and omized into two groups . Initially , all had to pass a basic skill assessment ( 3 tasks ) . Then endoscopic small bowel biopsy was performed ( 8 times ) either with the in vitro PT ( group A ) or the in vivo AM ( group B ) . Finally , all had to demonstrate this procedure in the in vivo AM and repeat the Output:	The retrieved studies showed some encouraging trends in terms of trainee satisfaction with improvement after training , but the improvements were mainly on the training tool itself . Some tools have been proven to be construct-valid .
MS21643	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: & NA ; The placebo effect of transcutaneous electrical stimulation was studied in 93 patients in a double‐blind cross‐over trial using a genuine stimulator and a placebo machine . Placebo analgesic effects occurred in 32 % of trials , as compared with 48 % for actual stimulation . The placebo effect of the transcutaneous electrical stimulator is similar to the placebo effect that is noted in other double‐blind studies in which medicationms are used The aim of this study was to test the efficacy of shortterm transcutaneous electrical nerve stimulation ( TENS ) treatment in chronic pain with respect to pain intensity and patients ’ satisfaction with treatment results . We therefore performed a r and omised controlled trial comparing TENS and sham TENS . Patients , research ers and therapists were blinded for treatment allocation . One hundred and sixty-three patients with chronic pain referred to the Pain Centre entered the study . Conventional TENS and sham TENS were applied in the segments of pain , for a period of ten days . Outcome measures were pain intensity ( visual analogue scale ) and patients ’ satisfaction with treatment result ( yes or no ) . The proportions of patients satisfied with treatment result differed significantly for TENS compared to sham TENS ( 58 and 42.7 % respectively , x2=3.8 , p=0.05 ) . However , no differences in pain intensity were found for patients treated with TENS or sham TENS . Only for patients satisfied with treatment results pain intensity gradually decrease equally both for TENS and sham TENS with repeated treatment application OBJECTIVE Few non-surgical conditions are more painful than rib fractures . There are a few methods for pain relief in patients with minor rib fractures . METHODS We used a non-steroidal anti-inflammatory drug ( NSAID , Naproxen sodium ) and transcutaneous electrical nerve stimulator ( TENS ) to control pain of the patients with uncomplicated minor rib fractures . One hundred consecutive patients admitted to Kartal Education and Research Hospital Emergency Service , were r and omized into four groups . The patients were assigned to one of the following pain treatments : NSAID , TENS , NSAID plus inactive TENS or placebo . The patients used NSAIDs and placebo four times a day and TENS twice a day for 3 days . All patients were asked to assess their pain level with a scoring system on days 0 , 1 and 3 . RESULTS The most effective treatment was TENS on days 1 and 3 ( P<0.05 ) . Although NSAID and NSAID plus inactive TENS controlled pain better than placebo on day 1 ( P<0.05 ) , this superiority did not continue to day 3 ( P>0.05 ) . There was no difference between NSAID and NSAID plus inactive TENS in controlling pain on either days 1 or 3 . CONCLUSION We conclude that TENS was more effective than NSAID or placebo in patients with uncomplicated minor rib fractures , because of its prominent and admirable efficacy in reduction of pain Venipuncture continues to be considered a painful and unpleasant experience for those receiving medical treatment . A prospect i ve study investigating whether the application of a transcutaneous electrical nerve stimulator ( TENS ) decreases the complaints of pain and unpleasantness with i.v . needle insertion was conducted using a group of 71 subjects who were double-blinded and r and omized to one of three groups : TENS , placebo-TENS , and control . This article gives an overview of this research and describes its findings Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field OBJECTIVE This study examined the optimal stimulation duration of transcutaneous electrical nerve stimulation ( TENS ) for relieving osteoarthritic knee pain and the duration ( as measured by half-life ) of post-stimulation analgesia . SUBJECTS Thirty-eight patients received either : ( i ) 20 minutes ( TENS20 ) ; ( ii ) 40 minutes ( TENS40 ) ; ( iii ) 60 minutes ( TENS60 ) of TENS ; or ( iv ) 60 minutes of placebo TENS ( TENS(PL ) ) 5 days a week for 2 weeks . METHODS A visual analogue scale recorded the magnitude and pain relief period for up to 10 hours after stimulation . RESULTS By Day10 , a significantly greater cumulative reduction in the visual analogue scale scores was found in the TENS40 ( 83.40 % ) and TENS60 ( 68.37 % ) groups than in the TENS20 ( 54.59 % ) and TENS(PL ) ( 6.14 % ) groups ( p < 0.000 ) , such a group difference was maintained in the 2-week follow-up session ( p < 0.000 ) . In terms of the duration of post-stimulation analgesia period , the duration for the TENS40 ( 256 minutes ) and TENS60 ( 258 minutes ) groups was more prolonged than in the other 2 groups ( TENS20 = 168 minutes , TENS(PL ) = 35 minutes ) by Day10 ( p < 0.000 ) . However , the TENS40 group produced the longest pain relief period by the follow-up session . CONCLUSION 40 minutes is the optimal treatment duration of TENS , in terms of both the magnitude ( VAS scores ) of pain reduction and the duration of post-stimulation analgesia for knee osetoarthritis Thirty patients with chronic pain due to osteoarthrosis ( OA ) of the knee were enrolled in a r and omised double-blind cross-over trial of self-administered transcutaneous electrical nerve stimulation ( TENS ) and placebo TENS . Medication was st and ardised to paracetamol tablets only . As measured on visual analogue scales for pain relief 46 % of patients responded to active therapy and 43 % to placebo . The length of pain relief during active therapy was significantly longer than that during placebo . At the end of the trial more patients wanted to continue using active TENS in preference to placebo or their original medication . Although most of the parameters observed favoured active TENS , it was not possible to establish its clear superiority over placebo , because the response rate to placebo TENS was high and sustained for at least 3 weeks . This trial suggests that a longer study is required to establish the role of TENS as a therapeutic agent in the treatment of the pain of chronic arthritis Objective To assess the value of transcutaneous electrical nerve stimulation ( TENS ) during cervical laser therapy BACKGROUND AND PURPOSE It is not fully understood how transcutaneous electrical nerve stimulation ( TENS ) intensity affects mechanical pain threshold . METHOD Sixty-six healthy volunteers ( 13 male , 53 female ; 132 h and s ) without prior experience of TENS participated in the study , which comprised a r and omized single-blind controlled trial . TENS was administered for 20 minutes through electrodes ( 25 x 25 mm ) placed on the h and s and forearms with a fixed frequency of 100 Hz and pulse duration of 150 micros . TENS intensity was r and omized and allocated in a concealed manner so that one arm received TENS with stimulation intensity set at participants ' subjective sensory threshold and the other received TENS with stimulation intensity continuously adjusted by physiotherapists to a strong but comfortable non-painful stimulation . Observers were blinded to stimulation intensity levels . RESULTS Mechanical pain threshold increased significantly , by a mean total of 0.79 kg/cm2 ( 95 % confidence interval [ 95 % CI ] : 0.54 - 1.04 ) ( p < 0.001 ) on the strong but comfortable non-painful stimulation side . The mean change in mechanical pain threshold on the sensory threshold side was 0.19 kg/cm2 and did not reach statistical significance ( 95 % CI-0.15 to 0.51 ) . The mean stimulation intensity level for sensory threshold was 6.7 mA ( 95 % CI : 5.65 to 7.83 ) which was significantly lower ( p < 0.001 ) than the mean stimulation intensity for the strong stimulation , which was 20.5 mA ( 95 % CI 16.6 to 24.4 ) , respectively . The strong stimulation levels were , on average , 3.05 times higher than sensory threshold , but individual variations were large ( range 1.2 - 6.1 ) . CONCLUSIONS TENS administered at a strong but comfortable non-painful stimulation intensity increases mechanical pain threshold ipsi-laterally in healthy subjects , whereas TENS administered at sensory threshold intensity does not . TENS may be ineffective if electrodes are placed contralaterally or distant to the pain site and if stimulation intensity levels are not titrated to subjective strong levels . Further clinical trials are needed to clarify if these findings may also be generalized to population s of chronic pain sufferers A double-blind controlled analgesic study was undertaken in out patients suffering acute traumatic pain . One hundred patients completed the study and were r and omly assigned to four treatment groups , each receiving either functioning transcutaneous electrical nerve stimulators ( TENS ) , placebo TENS , acetaminophen with codeine and a functioning TENS , or acetaminophen with codeine and a placebo TENS . Pain was assessed prior to treatment , at 48 hours , and at one month using a visual analog scale . A statistically significant difference in pain relief occurred between the placebo and functioning TENS groups . The TENS was approximately as effective as acetaminophen ( 300 - 600 mg ) with codeine ( 30 - 60 mg ) but had no side effects . Transcutaneous electrical nerve stimulators have been shown to be effective in the management of acute traumatic pain and may be indicated for patients who can not be given medications & NA ; This study evaluated the effects of varying frequency , intensity and stimulation site , of transcutaneous electrical nerve stimulation ( TENS ) in an experimental model of pain . In a double‐blind design 240 volunteers were r and omised to one of six experimental TENS groups , a sham TENS or control ( n=30 per group ; gender balanced ) . Two TENS frequencies ( 110 or 4 Hz ) and two intensities ( strong but comfortable or highest tolerable ) at a fixed pulse duration ( 200 & mgr;s ) were applied at three sites relative to the measurement site ( segmentally , extrasegmentally or a combination of these ) , for 30 min . Pressure pain thresholds ( PPT ) were measured using a pressure algometer , in the first dorsal interosseous muscle , every 10 min , during stimulation and for a further 30 min . The high frequency , high intensity segmental , and combined stimulation groups , showed rapid onset and significant hypoalgesic effects . This effect was sustained for 20 min post‐stimulation in the high frequency segmental group . All other TENS intervention groups showed hypoalgesic responses similar to the sham TENS group , and none of these groups reached a clinical ly significant hypoalgesic level . Conclusions : The role of TENS frequency , intensity and site are pivotal to achieving optimal hypoalgesic effects , during and after stimulation . Clinical applications of these parameter combinations require further investigations Chronic pain associated with breast cancer treatment is becoming increasingly recognized . Patients with this condition can experience significant physical and psychological morbidity and may benefit from nonpharmacological interventions as part of a multidisciplinary team approach . We compared the effectiveness of transcutaneous electrical nerve stimulation ( TENS ) , transcutaneous spinal electroanalgesia ( TSE ) , and a placebo ( sham TSE ) in a r and omized controlled trial . The study sample comprised 41 women with chronic pain following breast cancer treatment , and outcome measures included pain report , pain relief , pain interference , anxiety and depression , arm mobility , and analgesic consumption . There was little evidence to suggest that TENS or TSE were more effective than placebo . All three interventions had beneficial effects on both pain report and quality of life , a finding that may be due to either psychophysical improvements result ing from the personal interaction involved in the treatment or a placebo response . Although electrical stimulation appears to be well tolerated in this population , further research is needed to establish its effectiveness for chronic cancer treatment-related pain Thirty-six non-hospitalized subjects with chronic pain from OA of the knee participated in an evaluation of transcutaneous electrical nerve stimulation ( TENS ) and naproxen , an NSAID . All pre-experiment Output:	Suboptimal dosing of TENS and inappropriate outcome assessment were particularly prevalent weaknesses indicating low fidelity . Poor implementation fidelity was identified as a significant source of bias in systematic review s of TENS studies and might explain lack of consistent treatment effects of TENS in pain .
MS21644	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In a large case – control study on breast cancer risk and serum hormone concentrations , nested within the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohort , we examined to what extent the relationship of excess body weight with breast cancer risk may be explained by changes in sex steroids . Height , weight , waist and hip circumferences , and serum measurements of testosterone [ T ] , and rostenedione [ Δ4 ] , dehydroepi and rosterone sulphate [ DHEAS ] , estradiol [ E2 ] , estrone [ E1 ] and sex‐hormone binding globulin [ SHBG ] were available for 613 breast cancer cases , and 1,139 matched controls , who were all menopausal at the time of blood donation . Free T [ fT ] and free E2 [ fE2 ] were calculated using mass action equations . Breast cancer risk was related to body mass index ( BMI ) ( RR = 1.11 [ 0.99–1.25 ] , per 5 kg/m2 increase in BMI ) , and waist ( RR = 1.12 [ 1.02–1.24 ] , per 10 cm increase ) and hip circumferences ( RR = 1.14 [ 1.02–1.27 ] , per 10 cm increase ) . The increase in breast cancer risk associated with adiposity was substantially reduced after adjustment for any estrogens , especially for fE2 ( from 1.11 [ 0.99–1.25 ] to 0.99 [ 0.87–1.12 ] , from 1.12 [ 1.02–1.24 ] to 1.02 [ 0.92–1.14 ] and from 1.14 [ 1.02–1.27 ] to 1.05 [ 0.93–1.18 ] for BMI , waist and hip circumferences , respectively ) . A modest attenuation in excess risk was observed after adjustment for fT , but the remaining and rogens had little effect on the association of body adiposity with breast cancer . Our data indicate that the relationship of adiposity with breast cancer in postmenopausal women could be partially explained by the increases in endogenous estrogens , and by a decrease in levels of SHBG . © 2005 Wiley‐Liss , Introduction Overweight and obesity in childhood and adolescence are associated with reduced breast cancer risk , independent of adult body mass index ( BMI ) . These associations may be mediated through breast density . Methods We prospect ively examined associations of early life body fatness with adult breast density measured by MRI in 182 women in the Dietary Intervention Study in Children ( DISC ) who were ages 25–29 at follow-up . Height , weight , and other factors were measured at baseline ( ages 8–10 ) and annual clinic visits through adolescence . We used linear mixed-effects models to quantify associations of percent breast density and dense and non-dense breast volume at ages 25–29 with quartiles of age-specific youth body mass index ( BMI ) Z-scores , adjusting for clinic , treatment group , current adult BMI , and other well-established risk factors for breast cancer and predictors of breast density . Results We observed inverse associations between age-specific BMI Z-scores at all youth clinic visits and percent breast density , adjusting for current adult BMI and other covariates ( all p values < 0.01 ) . Women whose baseline BMI Z-scores ( at ages 8–10 years ) were in the top quartile had significantly lower adult breast density , after adjusting for current adult BMI and other covariates [ least squares mean ( LSM ) : 23.4 % ; 95 % confidence interval ( CI ) : 18.0 % , 28.8 % ] compared to those in the bottom quartile ( LSM : 31.8 % ; 95 % CI : 25.2 % , 38.4 % ) ( p trend < 0.01 ) . Significant inverse associations were also observed for absolute dense breast volume ( all p values < 0.01 ) , whereas there were no clear associations with non-dense breast volume . Conclusions These results support the hypothesis that body fatness during childhood and adolescence may play an important role in premenopausal breast density , independent of current BMI , and further suggest direct or indirect influences on absolute dense breast volume . Clinical Trials Registration NumberNCT00458588 ; April 9 , Greater body fatness during childhood is associated with reduced risk of premenopausal breast cancer , but few studies have addressed the relation of adiposity with sex hormones in girls . We prospect ively examined associations between adiposity and circulating levels of sex hormones and sex hormone – binding globulin ( SHBG ) among 286 girls in the Dietary Intervention Study in Children . Participants were 8 to 10 years old at baseline and were followed for an average of 7 years . Anthropometric measurements were taken at baseline and at subsequent annual visits , and blood sample s were collected every 2 years . Concentrations of dehydroepi and rosterone sulfate ( DHEAS ) during follow-up were higher among girls with greater body mass index ( BMI ) at baseline . The mean for the lowest BMI quartile was 63.0 μg/dL compared with 78.8 μg/dL for the highest quartile , and each kg/m2 increment in baseline BMI was associated with a 4.3 % increase ( 95 % confidence interval , 1.6 - 7.0 % ) in DHEAS levels during follow-up ( Ptrend = 0.002 ) . Concentrations of SHBG during follow-up were lower among girls with greater BMI at baseline . The mean for the lowest BMI quartile was 94.8 nmol compared with 57.5 nmol for the highest quartile , and each kg/m2 increment in baseline BMI was associated with an 8.8 % decrease ( 95 % confidence interval , 7.0 - 10.6 % ) in SHBG levels during follow-up ( Ptrend < 0.0001 ) . Estrogen and progesterone concentrations were similar across BMI quartiles . These findings suggest that adiposity may alter DHEAS and SHBG levels in girls . Whether and how these differences affect breast development and carcinogenesis requires further research . ( Cancer Epidemiol Biomarkers Prev 2007;16(9):1880–8 Abstract Obesity , physical inactivity , and sedentary behavior , concomitants of the modern environment , are potentially modifiable breast cancer risk factors . This study investigated the association of anthropometric measurements , physical activity and sedentary behavior , with the risk of incident , invasive breast cancer using a prospect i ve cohort of women enrolled in the Canadian Study of Diet , Lifestyle and Health . Using a case-cohort design , an age-stratified subcohort of 3,320 women was created from 39,532 female participants who returned completed self-administered lifestyle and dietary question naires at baseline . A total of 1,097 incident breast cancer cases were identified from the entire cohort via linkage to the Canadian Cancer Registry . Cox regression models , modified to account for the case-cohort design , were used to estimate hazard ratios ( HR ) and 95 % confidence intervals ( CI ) for the association between anthropometric characteristics , physical activity , and the risk of breast cancer . Weight gain as an adult was positively associated with risk of post-menopausal breast cancer , with a 6 % increase in risk for every 5 kg gained since age 20 ( HR 1.06 ; 95 % CI 1.01–1.11 ) . Women who exercised more than 30.9 metabolic equivalent task ( MET ) hours per week had a 21 % decreased risk of breast cancer compared to women who exercised less than 3 MET hours per week ( HR 0.79 ; 95 % CI 0.62–1.00 ) , most evident in pre-menopausal women ( HR 0.62 ; 95 % CI 0.43–0.90 ) . As obesity reaches epidemic proportions and sedentary lifestyles have become more prevalent in modern population s , programs targeting adult weight gain and promoting physical activity may be beneficial with respect to reducing breast cancer morbidity The prevalence of obesity at all ages is increasing epidemically worldwide . Information on the association between premenopausal breast cancer and body size during childhood and teenage years is scarce . In 1991 to 1992 , a prospect i ve cohort study was assembled in Norway and Sweden . We included in the analysis presented here 99,717 premenopausal women . During the follow-up period , which ended in December 1999 , 733 of these women developed a primary invasive breast cancer . Overweight and obesity [ body mass index ( BMI ) > 25 kg/m(2 ) ] at enrollment was associated with a decreased risk of premenopausal breast cancer ( P for linear trend = 0.007 ) . Apparent associations between perceived body shape at age 7 and BMI at age 18 , with heavier builds at both ages seemingly being protective for premenopausal breast cancer risk , lost their statistical significance after adjustment for BMI at cohort enrollment . Body size at age 7 was correlated with BMI at age 18 ( r = 0.43 ) ; BMI at age 18 was correlated with adult BMI ( r = 0.48 ) . Changes in body size from age 7 or 18 to adulthood did not affect per se risk of premenopausal breast cancer risk . Height was related to risk , with a statistically significantly 30 % reduced risk only in women shorter than 160 cm as compared with taller ones . The decreased risk of premenopausal breast cancer was observed in overweight and obese women without , but not in those with , a family history of breast cancer This study was conducted to assess the relation between body size and risk of breast cancer among young women . A case-control study was conducted among women aged 21 - 45 years living in three counties in Washington State . Cases were women born after 1944 with invasive or in situ breast cancer that was diagnosed between January 1 , 1983 , and April 30 , 1990 . Controls were selected using r and om digit dialing and were frequency-matched to cases on the basis of age and county of residence . Interviews took place between 1986 and 1992 . Body size was evaluated using indices from several different time periods . After adjustment for confounders , a decreased risk of breast cancer was found for women in the highest quintile of body mass index ( weight (kg)/height (m)2 ) as compared with the lowest quintile ( for maximum lifetime body mass index , odds ratio = 0.69 , 95 % confidence interval ( CI ) 0.51 - 0.94 ) . Age modified the relation between body size and risk of breast cancer . The odds ratio for women in the highest quintile of maximum body mass index who were aged 21 - 35 years was 0.29 ( 95 % CI 0.16 - 0.55 ) , as compared with an odds ratio of 1.5 for women aged 36 - 45 years ( 95 % CI 0.9 - 2.5 ) ( p for interaction = 0.003 ) . This study supports prior research showing a decreased risk of breast cancer associated with increased body size among premenopausal or young women . More detailed analysis in this study found a strong effect that was limited to the youngest age group ( < or = 35 years ) Few prospect i ve studies have investigated the association between BMI at age 20 years ( BMI 20y ) and breast cancer risk with consideration to estrogen/progesterone receptor status ( ER/PR ) . We evaluated the association between BMI 20y and ER/PR‐defined breast cancer risk among 41,594 women in the population ‐based Japan Public Health Center‐based Prospect i ve Study . Anthropometric factors were assessed using self‐reported question naires . Relative risks ( RRs ) were estimated by Cox proportional hazards regression models . Through to the end of 2006 , 452 breast cancer cases were identified . We observed a statistically significant inverse association between BMI 20y and breast cancer incidence [ multivariable‐adjusted RR for each 5‐unit increment 0.75 ( 95%CI = 0.61–0.92 ) ] , which was not modified by menopausal or recent BMI status . In contrast , recent BMI and subsequent BMI gain were not associated with increased risk among premenopausal women , but were substantially associated with increased risk among postmenopausal women [ corresponding RRrecent BMI = 1.31 ( 95%CI = 1.07–1.59 ) ; RRsubsequent BMI gain = 1.32 ( 95%CI = 1.09–1.60 ) ] . In subanalyses by receptor status ( ∼50 % of cases ) , the observed inverse association of BMI 20y with risk was consistent with the result for ER – PR– [ 0.49 ( 95%CI = 0.27–0.88 ) ] , while the observed positive associations of BMI gain with postmenopausal breast cancer risk appeared to be confined to ER+PR+ tumors [ corresponding RRfor subsequent BMI gain = 2.24 ( 95%CI = 1.50–3.34 ) ] . Low BMI at age 20 years was substantially associated with an increased risk of breast cancer . In contrast , high recent BMI and subsequent BMI gain from age 20 were associated with increased risk of postmenopausal ER+PR+ tumors OBJECTIVES We sought to determine whether social class modifies the effect of BMI on breast cancer incidence . METHODS Participants included 5642 postmenopausal White women recruited in 1989 to CLUE II , a prospect i ve coh Output:	The results remained unchanged after the trim and fill method was applied to correct the bias . In summary , higher body fatness at a young age may have a protective role in the later development of breast cancer in both premenopausal and postmenopausal women . However , this potential benefit should not be overemphasized , as our findings suggest that increased body fatness gain from a young age is positively associated with postmenopausal breast cancer risk .
MS21645	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The objective of this study was to compare the impact of closed- versus open-ended question formats on the completeness and accuracy of demographic data collected in a mailed survey question naire . We surveyed general internists in five Canadian provinces to determine their career satisfaction . We r and omized respondents to receive versions of the question naire in which 16 demographic questions were presented in a closed-ended or open-ended format . Two questions required respondents to make a relatively simple computation ( ensuring that three or four categories of response added to 100 % ) . The response rate was 1007/1192 physicians ( 80.0 % ) . The proportion of respondents with no missing data for all 16 questions was 44.7 % for open-ended and 67.0 % for closed-ended formats ( P < 0.001 ) . The odds of having missing items remained higher for open-ended response options after adjusting for a number of respondent characteristics ( 2.67 , 95 % confidence interval 2.01 to 3.55 ) . For the two questions requiring computations focused on professional activity and income , there were more missing data ( P = 0.02 , 0.02 , respectively ) but fewer inaccurate responses ( P = 0.009 , 0.20 , respectively ) for the open-ended compared to the closed-ended format . Investigators can achieve higher response rates for demographic items using closed format response options , but at the risk of increasing inaccuracy in response to questions requiring computation STUDY OBJECTIVE --The aim of the study was to determine whether complete anonymity improves the response rates to a postal question naire . DESIGN --The study derived from a series of postal surveys on AIDS knowledge conducted on six different date s in 1986 and 1987 . The sample was r and omly divided into two , each group being sent the same question naire . One group was informed that the replies were anonymous , the other that they were not . The latter were sent reminders . SETTING --Recipients of the question naires were drawn from the Southampton electoral rolls . PARTICIPANTS --300 people in each survey ( total 1800 ) were sent question naires , representing on each occasion a different 1:500 systematic sample . RESULTS --Response rate was 49 % for the anonymous question naires and 51 % for the numbered question naires . Reminders boosted the response in the numbered group to 72 % . CONCLUSIONS --There is no evidence that anonymity improves response to postal question naires , but the use of reminders may do so Postal health surveys in the general population can provide important information to assist with planning and service provision . 1 High response rates are needed to ensure validity and to minimize costs from following-up non-responders . 2 Only a small number of studies have examined methods to increase response rates in postal surveys . Using a post-office stamp rather than a prepaid business reply envelope may seem more personal and encourage participants to return the question naire . However , results from trials evaluating this are inconsistent and limited to health professionals in North America . 3–5 Consequently there is little evidence to inform the choice of reply envelopes in postal surveys of the general UK population . This was determined in the current study . Methods The sample consisted of 633 adults r and omly selected from a health authority register in the north west of Engl and . A computer-generated r and omization list , stratifying on sex and age ( 18–45 , 46–64 , у65 years ) was used to allocate participants to receive one of two types of reply envelopes , both printed with the return address . One group ( POS ) received a reply envelope with a first-class post-office stamp , while the second group ( PPB ) received a prepaid business-franked envelope to return their health question naire . The initial mail-out included the 16-page health question naire , a personalized letter from the Director of Public Health and one of the two return envelopes . Question naires were sent out in March 2001 and non-responders were sent a reminder postcard 10 days later . The primary outcome was the difference in response rates between the two types of reply envelopes , after follow-up reminders had been sent measured at 4 weeks after posting the survey . The χ 2 test was used to examine statistical significance . Approval was obtained for the study from the Local Research Ethics Committee.2 % ) question naires were returned within 10 days , from the two allocation groups , respectively . After sending reminders to the 182 non-responders in the POS group and 195 in the PPB group ( excluding 6 and 4 participants respectively later found to be not living at that address ) , the return rate increased to 182 ( 58.7 % ) and 179 ( 57.2 % ) in the two groups . This difference of 1.5 % between the two groups is unlikely to be important and was not statistically significant ( χ 2 = 0.08 , P = 0.77 ) . No important difference was observed in return rates between the POS and the PPB group for men or women and across three age groups . However , return rates Mailing surveys to low-income population s is often avoided because of concern about low response rates . In this study , the authors used a mailed survey of a low-income population to test whether $ 1.00 or $ 2.00 cash-response incentives were worth the expense and whether 2-day priority mail ( $ 2.90 postage ) would yield a sufficiently higher response rate than certified mail ( $ 1.52 postage ) to justify its cost . In 1994 , 2,243 r and omly selected families in subsidized health care programs in Pierce County , Washington , were r and omly sent no incentive , $ 1.00 , or $ 2.00 in the first of three mailings . For the third mailing , nonrespondents were r and omly assigned to receive either certified or 2-day priority mail . After 4 weeks , the response rates were 36.7 % , 48.1 % , and 50.3 % for the no-incentive , $ 1.00 , and $ 2.00 groups , respectively . After three mailings , the cost per response was the lowest for the group that received $ 1.00 . The response rate for the certified mailing ( 28.1 % ) was significantly higher than the rate for the more expensive priority mailing ( 21.7 % ) . No incentive-related bias was detected . The authors concluded that the most efficient protocol for this low-income population was to use a $ 1.00 incentive in the first mailing and a certified third mailing OBJECTIVES The effects of incentive size on physicians ' response rates to a mail survey were determined . METHODS One thous and US primary care physicians were assigned r and omly to receive a survey with either a $ 5 bill or a $ 2 bill as an incentive . For each of the two incentive groups , the overall response rate for three mailing waves , the total cost , and the total cost per usable response were measured . RESULTS The response rate among those receiving the $ 5 bill ( 61 % ) was 32 % higher than the response rate among those receiving the $ 2 bill ( 46 % ) ; overall costs were slightly higher in the $ 5 group , but the cost per response for each group was similar ( $ 15.46 versus $ 14.93 ) . For the same cost , a higher response rate could have been achieved in the $ 2 group if costs saved from foregoing the third mailing were instead used to increase the incentive for a portion of the subjects . CONCLUSIONS A $ 5 bill incentive yielded a higher response rate among the physicians in this study than did a $ 2 bill incentive . Moreover , the powerful effect of the incentive size , combined with the consequent decline in the costs of subsequent mailing waves , suggests that re sources in a fixed survey budget are allocated more efficiently to increasing the initial incentive rather than to providing a third wave to nonresponders We studied women 45 - 54 years of age from two communities who failed to return a mailed survey in an experiment to assess the impact on interviewing response rates of leaving messages on telephone answering machines at the time of telephone follow-up . There were 88 and 103 subjects assigned to the " message " and " no message " groups , respectively . After adjustment for age , interviewer , and community , leaving messages increased the rate of reaching a household by about 15 % and improved the overall interviewing response rate by about 15 % as well . This improvement was more apparent in women from the higher socioeconomic status community Study objective : To assess the effectiveness of a telephone reminder in increasing responses to postal surveys and to calculate the differential costs per completed question naire . Design : R and omised controlled trial . Setting : Australian university and rehabilitation medicine practice . Participants : The trial was conducted in 1999 among the 143 non-respondents to a question naire about work related neck and upper body disorders . The question naire was sent to two Australian female sample s : 200 office workers ( Sample A ) and 92 former rehabilitation medicine patients ( Sample B ) . A reminder letter , another copy of the question naire and a final letter were sent at two week intervals . Half of the non-respondents within each sample were r and omly selected to receive a telephone reminder just after the second mailout of the question naire . All direct costs were calculated . Main results : Responses were significantly higher among those who received the telephone reminder intervention ( relative risk 2.54 , 95 % confidence intervals 1.43 to 4.52 ) . Analysed by intention to phone , 47 % of non-respondents in Sample A and 38 % in Sample B returned a complete question naire after the intervention , compared with 21 % and 10 % , respectively , in the control groups . For the 112 women ( combined sample s ) who returned completed question naires before r and omisation , the average cost per respondent was AUD14 . There was a higher total cost for the intervention groups ( AUD851 versus AUD386 for controls ) , but the significantly higher number of additional completed responses ( 31 versus 12 ) result ed in a 15 % lower marginal cost per completed question naire in those groups . Conclusion : Telephone reminders are cost effective in improving responses to postal surveys OBJECTIVES To assess the impact of patient satisfaction survey method on response rate , data quality and satisfaction . PATIENTS AND METHODS Four modes of data collection were assessed during a r and omized trial that included 400 in patients discharged from a teaching hospital . RESULTS The response rate was 58 % within the mail survey group ( 72 % with follow-up letter ) versus 73 % and 81 % within the home and telephone interview group ( p < 0.01 ) . 69 % of the mailed question naires contained no missing values versus 94 % and 96 % for home and telephone interview modes ( p < 0.01 ) . The global satisfaction scale score was greater within the mail survey groups ( 8.1/10 without follow-up letter and 7.9 with follow-up letter ) than within the telephone interview group ( 7.8 ) and the face to face interview group ( 7.3 ) , ( p < 0.05 ) . CONCLUSION Mail survey with follow-up letter constitutes an operational method despite lower data quality and overestimation of patients ' satisfaction scores Although self-administered question naires are major sources of information in epidemiology , comparatively little has been done to study practical aspects of design and mailing . The objective of this study was to evaluate various measures taken to increase the response rate . A question naire was mailed in July 1995 to a r and om sample ( n = 2,000 ) of the Swedish population aged 20 - 79 years . Using a r and omized factorial study design , the question naire and mailing procedures were changed in three ways : preliminary notification , length of the question naire , and mention of telephone contact . The overall question naire retrieval rate was 49 % . Preliminary notification ( adjusted odds ratio of receiving a completed question naire = 1.30 , 95 % confidence interval ( CI ) 1.08 - 1.56 relative to the absence of preliminary notification ) and short length of the question naire ( odds ratio = 1.24 , 95 % CI 1.04 - 1.48 relative to a long question naire ) were both independently associated with a higher retrieval rate . Of eight possible combinations , the one comprising preliminary notification , a short question naire , and no mention of telephone contact gave the highest retrieval rate , 56 % . The lowest retrieval rate , 40 % , was observed for the combination of no preliminary notification , a long question naire , and mention of telephone contact . Young age , male sex , and urban residence significantly lowered the retrieval rate . Although there was a positive association between the question naire retrieval rate and partial nonresponse ( missing answers in retrieved question naires ) , the marginal losses due to the latter did not cancel the gains by optimized mailing routines . Old age was the strongest determinant of partial nonresponse . The data provide evidence that design and mailing strategies , as well as demographic characteristics , may greatly influence the response rate of mailed epidemiologic question naires BACKGROUND A range of factors have been shown to affect the response rate to mailed question naires , but particular strategies to improve patients ' response in trials conducted in general practice require further study . METHODS Non-responders in a larger trial were r and omized to receive a telephone or recorded delivery reminder on the third contact . The cost of administration of each method was estimated . RESULTS Significantly more patients returned completed question naires when sent question naires by recorded delivery , although the cost per patient contacted was nearly three times more than for contact by telephone . CONCLUSION Our study indicates that sending reminders by recorded delivery , although more expensive , is more effective than telephone reminders for recruiting patients to a study in general practice using research question naires In two experiments , findings with college undergraduates ( Ns = 154 and 137 ) suggest social desirability may not affect responses to survey items on HIV-related behaviors and results may not be constrained by anonymity In this study , the authors sought to determine the effects of length and clarity on response rates and data quality for two food frequency question naires ( FFQs ) : the newly developed 36- Output:	Health research ers using postal question naires can increase response rates using the strategies shown to be effective in this systematic review
MS21646	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Summary Background Unnecessary antibiotic prescribing contributes to antimicrobial resistance . In this trial , we aim ed to reduce unnecessary prescriptions of antibiotics by general practitioners ( GPs ) in Engl and . Methods In this r and omised , 2 × 2 factorial trial , publicly available data bases were used to identify GP practice s whose prescribing rate for antibiotics was in the top 20 % for their National Health Service ( NHS ) Local Area Team . Eligible practice s were r and omly assigned ( 1:1 ) into two groups by computer-generated allocation sequence , stratified by NHS Local Area Team . Participants , but not investigators , were blinded to group assignment . On Sept 29 , 2014 , every GP in the feedback intervention group was sent a letter from Engl and 's Chief Medical Officer and a leaflet on antibiotics for use with patients . The letter stated that the practice was prescribing antibiotics at a higher rate than 80 % of practice s in its NHS Local Area Team . GPs in the control group received no communication . The sample was re-r and omised into two groups , and in December , 2014 , GP practice s were either sent patient-focused information that promoted reduced use of antibiotics or received no communication . The primary outcome measure was the rate of antibiotic items dispensed per 1000 weighted population , controlling for past prescribing . Analysis was by intention to treat . This trial is registered with the IS RCT N registry , number IS RCT N32349954 , and has been completed . Findings Between Sept 8 and Sept 26 , 2014 , we recruited and assigned 1581 GP practice s to feedback intervention ( n=791 ) or control ( n=790 ) groups . Letters were sent to 3227 GPs in the intervention group . Between October , 2014 , and March , 2015 , the rate of antibiotic items dispensed per 1000 population was 126·98 ( 95 % CI 125·68–128·27 ) in the feedback intervention group and 131·25 ( 130·33–132·16 ) in the control group , a difference of 4·27 ( 3·3 % ; incidence rate ratio [ IRR ] 0·967 [ 95 % CI 0·957–0·977 ] ; p<0·0001 ) , representing an estimated 73 406 fewer antibiotic items dispensed . In December , 2014 , GP practice s were re-assigned to patient-focused intervention ( n=777 ) or control ( n=804 ) groups . The patient-focused intervention did not significantly affect the primary outcome measure between December , 2014 , and March , 2015 ( antibiotic items dispensed per 1000 population : 135·00 [ 95 % CI 133·77–136·22 ] in the patient-focused intervention group and 133·98 [ 133·06–134·90 ] in the control group ; IRR for difference between groups 1·01 , 95 % CI 1·00–1·02 ; p=0·105 ) . Interpretation Social norm feedback from a high-profile messenger can substantially reduce antibiotic prescribing at low cost and at national scale ; this outcome makes it a worthwhile addition to antimicrobial stewardship programmes . Funding Public Health Engl and Although self-enhancement is linked to psychological benefits , it is also associated with personal and interpersonal liabilities ( e.g. , excessive risk taking , social exclusion ) . Hence , structuring social situations that prompt people to keep their self-enhancing beliefs in check can confer personal and interpersonal advantages . The authors examined whether accountability can serve this purpose . Accountability was defined as the expectation to explain , justify , and defend one 's self-evaluations ( grade s on an essay ) to another person ( " audience " ) . Experiment 1 showed that accountability curtails self-enhancement . Experiment 2 ruled out audience concreteness and status as explanations for this effect . Experiment 3 demonstrated that accountability-induced self-enhancement reduction is due to identifiability . Experiment 4 documented that identifiability decreases self-enhancement because of evaluation expectancy and an accompanying focus on one 's weaknesses Abstract Objective To determine whether a behavioral intervention delivered through a video game can improve the appropriateness of trauma triage decisions in the emergency department of non-trauma centers . Design R and omized clinical trial . Setting Online intervention in national sample of emergency medicine physicians who make triage decisions at US hospitals . Participants 368 emergency medicine physicians primarily working at non-trauma centers . A r and om sample ( n=200 ) of those with primary outcome data was reassessed at six months . Interventions Physicians were r and omized in a 1:1 ratio to one hour of exposure to an adventure video game ( Night Shift ) or apps based on traditional didactic education ( myATLS and Trauma Life Support MCQ Review ) , both on iPads . Night Shift was developed to recalibrate the process of using pattern recognition to recognize moderate-severe injuries ( representativeness heuristics ) through the use of stories to promote behavior change ( narrative engagement ) . Physicians were r and omized with a 2 × 2 factorial design to intervention ( game v traditional education apps ) and then to the experimental condition under which they completed the outcome assessment tool ( low v high cognitive load ) . Blinding could not be maintained after allocation but group assignment was masked during the analysis phase . Main outcome measures Outcomes of a virtual simulation that included 10 cases ; in four of these the patients had severe injuries . Participants completed the simulation within four weeks of their intervention . Decisions to admit , discharge , or transfer were measured . The proportion of patients under-triaged ( patients with severe injuries not transferred to a trauma center ) was calculated then ( primary outcome ) and again six months later , with a different set of cases ( primary outcome of follow-up study ) . The secondary outcome was effect of cognitive load on under-triage . Results 149 ( 81 % ) physicians in the game arm and 148 ( 80 % ) in the traditional education arm completed the trial . Of these , 64/100 ( 64 % ) and 58/100 ( 58 % ) , respectively , completed re assessment at six months . The mean age was 40 ( SD 8.9 ) , 283 ( 96 % ) were trained in emergency medicine , and 207 ( 70 % ) were ATLS ( advanced trauma life support ) certified . Physicians exposed to the game under-triaged fewer severely injured patients than those exposed to didactic education ( 316/596 ( 0.53 ) v 377/592 ( 0.64 ) , estimated difference 0.11 , 95 % confidence interval 0.05 to 0.16 ; P<0.001 ) . Cognitive load did not influence under-triage ( 161/308 ( 0.53 ) v 155/288 ( 0.54 ) in the game arm ; 197/300 ( 0.66 ) v 180/292 ( 0.62 ) in the traditional educational apps arm ; P=0.66 ) . At six months , physicians exposed to the game remained less likely to under-triage patients ( 146/256 ( 0.57 ) v 172/232 ( 0.74 ) , estimated difference 0.17 , 0.09 to 0.25 ; P<0.001 ) . No physician reported side effects . The sample might not reflect all emergency medicine physicians , and a small set of cases was used to assess performance . Conclusions Compared with apps based on traditional didactic education , exposure of physicians to a theoretically grounded video game improved triage decision making in a vali date d virtual simulation . Though the observed effect was large , the wide confidence intervals include the possibility of a small benefit , and the real world efficacy of this intervention remains uncertain . Trial registration clinical trials.gov ; NCT02857348 ( initial study ) /NCT03138304 ( follow-up ) Background The frequency of head computed tomography ( CT ) imaging for mild head trauma patients has raised safety and cost concerns . Vali date d clinical decision rules exist in the published literature and on-line sources to guide medical image ordering but are often not used by emergency department ( ED ) clinicians . Using simulation , we explored whether the presentation of a clinical decision rule ( i.e. Canadian CT Head Rule - CCHR ) , findings from mal practice cases related to clinicians not ordering CT imaging in mild head trauma cases , and estimated patient out-of-pocket cost might influence clinician brain CT ordering . Underst and ing what type and how information may influence clinical decision making in the ordering advanced medical imaging is important in shaping the optimal design and implementation of related clinical decision support systems . Methods Multi-center , double-blinded simulation-based r and omized controlled trial . Following st and ardized clinical vignette presentation , clinicians made an initial imaging decision for the patient . This was followed by additional information on decision support rules , mal practice outcome review , and patient cost ; each with opportunity to modify their initial order . The mal practice and cost information differed by assigned group to test the any temporal relationship . The simulation closed with a second vignette and an imaging decision . Results One hundred sixteen of the 167 participants ( 66.9 % ) initially ordered a brain CT scan . After CCHR presentation , the number of clinicians ordering a CT dropped to 76 ( 45.8 % ) , representing a 21.1 % reduction in CT ordering ( P = 0.002 ) . This reduction in CT ordering was maintained , in comparison to initial imaging orders , when presented with mal practice review information ( p = 0.002 ) and patient cost information ( p = 0.002 ) . About 57 % of clinicians changed their order during study , while 43 % never modified their imaging order . Conclusion This study suggests that ED clinician brain CT imaging decisions may be influenced by clinical decision support rules , patient out-of-pocket cost information and findings from mal practice case review .Trial registration NCT03449862 , February 27 , 2018 , Retrospectively registered Background Inappropriate antibiotic prescribing for nonbacterial infections leads to increases in the costs of care , antibiotic resistance among bacteria , and adverse drug events . Acute respiratory infections ( ARIs ) are the most common reason for inappropriate antibiotic use . Most prior efforts to decrease inappropriate antibiotic prescribing for ARIs ( e.g. , educational or informational interventions ) have relied on the implicit assumption that clinicians inappropriately prescribe antibiotics because they are unaware of guideline recommendations for ARIs . If lack of guideline awareness is not the reason for inappropriate prescribing , educational interventions may have limited impact on prescribing rates . Instead , interventions that apply social psychological and behavioral economic principles may be more effective in deterring inappropriate antibiotic prescribing for ARIs by well-informed clinicians . Methods / design The Application of Behavioral Economics to Improve the Treatment of Acute Respiratory Infections ( BEARI ) Trial is a multisite , cluster-r and omized controlled trial with practice as the unit of r and omization . The primary aim is to test the ability of three interventions based on behavioral economic principles to reduce the rate of inappropriate antibiotic prescribing for ARIs . We r and omized practice s in a 2 × 2 × 2 factorial design to receive up to three interventions for non-antibiotic-appropriate diagnoses : 1 ) Accountable Justifications : When prescribing an antibiotic for an ARI , clinicians are prompted to record an explicit justification that appears in the patient electronic health record ; 2 ) Suggested Alternatives : Through computerized clinical decision support , clinicians prescribing an antibiotic for an ARI receive a list of non-antibiotic treatment choices ( including prescription options ) prior to completing the antibiotic prescription ; and 3 ) Peer Comparison : Each provider ’s rate of inappropriate antibiotic prescribing relative to top-performing peers is reported back to the provider periodically by email . We enrolled 269 clinicians ( practicing attending physicians or advanced practice nurses ) in 49 participating clinic sites and collected baseline data . The primary outcome is the antibiotic prescribing rate for office visits with non-antibiotic-appropriate ARI diagnoses . Secondary outcomes will examine antibiotic prescribing more broadly . The 18-month intervention period will be followed by a one year follow-up period to measure persistence of effects after interventions cease . Discussion The ongoing BEARI Trial will evaluate the effectiveness of behavioral economic strategies in reducing inappropriate prescribing of antibiotics . Trials registration Clinical Trials.gov : PURPOSE We wanted to evaluate novel decision aids design ed to help patients trust and accept the controversial , evidence -based , US Preventive Services Task Force recommendations about prostate cancer screening ( from 2012 ) and mammography screening for women aged 40 to 49 years ( from 2009 ) . METHODS We created recorded vignettes of physician-patient discussion s about prostate cancer screening and mammography , accompanied by illustrative slides , based on principles derived from preceding qualitative work and behavioral science literature . We conducted a r and omized crossover study with repeated measures with 27 men aged 50 to 74 years and 35 women aged 40 to 49 years . All participants saw a video intervention and a more traditional , paper-based decision aid intervention in r and om order . At entry and after seeing each intervention , they were surveyed about screening intentions , perceptions of benefits and harm , and decisional conflict . RESULTS Changes in screening Output:	RESULTS We found that 10 behavioral economics concepts with nine cognitive biases were addressed and investigated for clinician decision-making , and that the following five concepts , which were actively explored , had an impact in CDS applications : social norms , framing effect , status-quo bias , heuristics , and overconfidence bias . CONCLUSIONS Our review revealed that the use of behavioral economics techniques is increasing in areas such as antibiotics prescribing and preventive care , and that additional tests of the concepts and heuristics described would be useful in other areas of CDS .
MS21647	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Migraine frequently co-occurs with and is triggered by sleep disturbance , particularly insomnia , and the large majority of patients with chronic migraine ( CM ) have comorbid insomnia . Limited evidence suggests that behavioral regulation of sleep may reduce migraine frequency , but studies to date have not assessed the viability of stimulus control and sleep restriction interventions or included objective measurement of sleep parameters . The aim of this study , thus , was to pilot-test the efficacy of a brief behavioral insomnia intervention for adults with CM and comorbid insomnia ; headache diaries and actigraphy were included to assess outcomes throughout the trial . METHODS This r and omized parallel-arm pilot trial recruited adults with both CM and comorbid insomnia . Participants were r and omly assigned to three 30-minute biweekly sessions of cognitive-behavioral therapy for insomnia ( CBTi ) or control treatment . Participants were blinded to treatment and control conditions to control for outcome expectations . Each treatment condition involved training in and daily practice in 5 instructions/skills . The CBTi group learned and practice d skills pertaining to stimulus control and sleep restriction . The control intervention was the same as used by Calhoun and Ford ( 2007 ) and involved training in and daily practice of skills pertaining to keeping a consistent food/liquid intake , range of motion exercises , and acupressure . Participants provided outcome data via daily headache diaries , actigraphy , and self-report measures . The primary outcome was reduction in headache frequency at 2 weeks post-treatment and 6-week follow-up ; secondary outcomes included other headache parameters , objective actigraphic and subjective changes in sleep , and treatment effect sizes and perceived credibility . Generalized estimating equations with a binomial logit link and inverse probability weights were used to assess the primary outcome among the intent-to-treat sample , and repeated measures generalized linear models were used to assess changes in secondary outcomes after controlling for baseline values . RESULTS The intent-to-treat analyses included 31 adults ( M age = 30.8 [ 12.9 ] years ; 90.3 % female ; 80.6 % white ) with CM and comorbid insomnia . Both interventions yielded reductions in headache frequency at post-treatment ( 26.9 % reduction for CBTi vs. 36.2 % for control ) and follow-up ( 48.9 % for CBTi vs. 25.0 % for control ) . At follow-up the odds of experiencing headache were 60 % lower for CBTi than for control treatment , indicative of a large effect size that did not reach statistical significance after Bonferroni correction for assessing two primary endpoints ( odds ratio : 0.40 ; 95 % CI : 0.17 , 0.91 ; P = .028 ) . CBTi produced significantly larger increases than control treatment in total sleep time and sleep efficiency as quantified by actigraphy , as well as in self-reported insomnia severity . Adherence was high and treatments were perceived as credible without differences between groups , but the control group experienced a higher rate of dropouts . No adverse events were reported . CONCLUSIONS Behavioral treatment of comorbid insomnia in individuals with CM produced large reductions in headache frequency , though some improvement in headache occurred with a behavioral intervention not focused on modifying sleep . Among the CBTi group only , both headache frequency and sleep parameters continued to improve after treatment , suggesting the presence of enduring effects over time . Directly treating insomnia using components of stimulus control and sleep restriction holds promise for reducing comorbid migraine . Development of and comparison to a truly inert pseudotherapy control presents unique challenges that future studies should address CONTEXT A previous cross-sectional study showed an association of migraine with a higher prevalence of magnetic resonance imaging (MRI)-measured ischemic lesions in the brain . OBJECTIVE To determine whether women or men with migraine ( with and without aura ) have a higher incidence of brain lesions 9 years after initial MRI , whether migraine frequency was associated with progression of brain lesions , and whether progression of brain lesions was associated with cognitive decline . DESIGN , SETTING , AND PARTICIPANTS In a follow-up of the 2000 Cerebral Abnormalities in Migraine , an Epidemiological Risk Analysis cohort , a prospect i ve population -based observational study of Dutch participants with migraine and an age- and sex-matched control group , 203 of the 295 baseline participants in the migraine group and 83 of 140 in the control group underwent MRI scan in 2009 to identify progression of MRI-measured brain lesions . Comparisons were adjusted for age , sex , hypertension , diabetes , and educational level . The participants in the migraine group were a mean 57 years ( range , 43 - 72 years ) , and 71 % were women . Those in the control group were a mean 55 years ( range , 44 - 71 years ) , and 69 % were women . MAIN OUTCOME MEASURES Progression of MRI-measured cerebral deep white matter hyperintensities , infratentorial hyperintensities , and posterior circulation territory infa rct like lesions . Change in cognition was also measured . RESULTS Of the 145 women in the migraine group , 112 ( 77 % ) vs 33 of 55 women ( 60 % ) in the control group had progression of deep white matter hyperintensities ( adjusted odds ratio [ OR ] , 2.1 ; 95%CI , 1.0 - 4.1 ; P = .04 ) . There were no significant associations of migraine with progression of infratentorial hyperintensities : 21 participants ( 15 % ) in the migraine group and 1 of 57 participants ( 2 % ) in the control group showed progression ( adjusted OR , 7.7 ; 95 % CI , 1.0 - 59.5 ; P = .05 ) or new posterior circulation territory infa rct like lesions : 10 of 203 participants ( 5 % ) in the migraine group but none of 83 in the control group ( P = .07 ) . There was no association of number or frequency of migraine headaches with progression of lesions . There was no significant association of high vs nonhigh deep white matter hyperintensity load with change in cognitive scores ( -3.7 in the migraine group vs 1.4 in the control group ; 95 % CI , -4.4 to 0.2 ; adjusted P = .07 ) . CONCLUSIONS In a community-based cohort followed up after 9 years , women with migraine had a higher incidence of deep white matter hyperintensities but did not have significantly higher progression of other MRI-measured brain changes . There was no association of migraine with progression of any MRI-measured brain lesions in men Objective To test whether behavioral weight loss ( BWL ) intervention decreases headaches in women with comorbid migraine and overweight/obesity . Methods This r and omized , single-blind trial allocated women [ 18–50 years old , 4–20 migraine days/month , Body Mass Index ( BMI ) = 25.0–49.9 kg/m2 ] to 16 weeks of BWL , ( n=54 ) that targeted exercise and eating behaviors for weight loss , or Migraine Education control ( ME , n=56 ) that delivered didactic instruction on migraine and treatments . Participants completed a 4-week smartphone headache diary at baseline , post-treatment ( 16–20 weeks ) and follow-up ( 32–36 weeks ) . The primary outcome was post-treatment change in migraine days/month , analyzed via linear mixed effects models . Results Of 110 participants r and omized , 85 ( 78 % ) and 80 ( 73 % ) completed post-treatment and follow-up . Although BWL achieved greater weight loss [ mean ( 95 % CI ) kg ] vs. ME at post-treatment [ −3.8 ( −2.5 , −5.0 ) vs. + 0.9 ( −0.4,2.2 ) p<.001 ] and follow-up [ −3.2 ( −2.0 , −4.5 ) vs. + 1.1 ( −0.2,2.4 ) , p<.001 ] , there were no significant group ( BWL vs. ME ) differences [ mean ( 95%CI ) ] migraine days/month at post-treatment [ −3.0 ( −2.0 , −4.0 ) vs. −4.0 ( −2.9 , −5.0 ) , p=.185 ] or follow-up [ −3.8 ( −2.7 , −4.8 ) vs. −4.4 ( −3.4 , −5.5 ) , p=.378 ] . Conclusion Contrary to hypotheses , BWL and ME yielded similar , sustained reductions in migraine headaches . Future research should evaluate whether adding BWL to st and ard pharmacologic and /or non-pharmacologic migraine treatment approaches yields greater benefits Chronic daily headache ( CDH ) , when defined as ≥ 15 headache days per month , affects 3 - 5 % of the adult population . Major life changes are putative precipitating events for onset of chronic pain , including chronic headache . This study compared the occurrence of specific life events between CDH cases and episodic headache controls in a community sample . CDH cases ( 180 + headache days per year : n = 206 ) and episodic headache controls ( 2 - 104 headache days per year : n = 507 ) were identified from a r and omly selected adult US population . Subjects were interviewed about the occurrence of certain major life changes or events ( change of residence , employment status , marital status , related to their children , deaths of relatives or close friends , and ‘ extremely stressful ’ ongoing situations ) occurring in a defined time period . Events that occurred during the same year or year before frequent headache onset in cases or in an equivalent time period in controls were considered to be antecedent events . Those that occurred after this time were considered subsequent events . Compared with episodic headache controls , CDH cases had more major life changes in the year before or same year as CDH onset . After adjusting for age , gender , headache type and year of event , the odds of CDH increased additionally with each antecedent event [ odds ratio ( OR ) 1.20 ( 1.1 , 1.3 ) , P < 0.001 ] , but not with subsequent events [ OR 0.94 ( 0.8 , 1.1 ) , P < 0.4 ] . In secondary analyses , the association between antecedent events and CDH was significant only for the approximately half of CDH cases who were aged ≥ 40 years [ OR 1.33 ( 1.2 , 1.50 ) vs. OR 1.04 ( 0.9 , 1.2 ) , P < 0.05 for interaction by age ] . These results suggest that major life changes are associated with the onset of chronic daily headache , particularly in middle age Objectives : Research increasingly suggests that obesity is an exacerbating factor for migraine . However , it is less clear whether weight loss may help to alleviate migraine in obese individuals . We examined whether weight loss after bariatric surgery is associated with improvements in migraine headaches . Methods : In this prospect i ve observational study , 24 patients who had migraine according to the ID-Migraine screener were assessed before and 6 months after bariatric surgery . At both time points , patients had their weight measured and reported on frequency of headache days , average headache pain severity , and headache-related disability over the past 90 days via the Migraine Disability Assessment question naire . Changes in headache measures and the relation of weight loss to these changes were assessed using paired- sample t tests and logistic regression , respectively . Results : Patients were mostly female ( 88 % ) , middle-aged ( mean age 39.3 ) , and severely obese ( mean body mass index 46.6 ) at baseline . Mean ( ±SD ) number of headache days was reduced from 11.1 ± 10.3 preoperatively to 6.7 ± 8.2 postoperatively ( p < 0.05 ) , after a mean percent excess weight loss ( % EWL ) of 49.4 % . The odds of experiencing a ≥50 % reduction in headache days was related to greater % EWL , independent of surgery type ( p < 0.05 ) . Reductions in severity were also observed ( p < 0.05 ) and the number of patients reporting moderate to severe disability decreased from 12 ( 50.0 % ) before surgery to 3 ( 12.5 % ) after surgery ( p < 0.01 ) . Conclusions : Severely obese migraineurs experience marked alleviation of headaches after significant weight reduction via bariatric surgery . Future studies are needed to determine whether more modest , behaviorally produced weight losses can effect similar migraine improvements . Classification of evidence : This study provides Class III evidence that bariatric surgery is associated with reduction of migraine headaches in severely obese individuals BACKGROUND Sleep problems have been linked with headaches for more than a century , but whether the headaches are the cause or the result of the disrupted sleep is unknown . OBJECTIVES We previously reported that nonrestorative sleep and poor sleep habits are almost universal in a referral population of women with transformed migraine ( TM ) . Since cognitive behavioral therapy is effective in improving sleep quality in individuals with poor sleep hygiene , we design ed a r and omized , placebo-controlled study to assess the impact of such treatment on TM . We hypothesized that behavioral sleep modification ( BSM ) would be associated with improvement in headache frequency and intensity and with reversion to episodic migraine . METHODS Subjects were 43 women with TM referred to an academic headache center . After obtaining informed consent , patients were r and omized to receive either behavioral sleep instructions or placebo behavioral instructions in addition to Output:	A range of risk factors for the new onset of CM/TM , CDH , or related chronic headache diseases were identified with the strongest data supporting increased headache day frequency , acute medication overuse/high-frequency use and depression , which are potentially modifiable risk factors . Development of central sensitization and increased activation of the trigeminal nociceptive pathways may be drivers of the new onset of CM or CDH .
MS21648	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objectives To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate ( quetiapine XR ) monotherapy in patients with major depressive disorder ( MDD ) . Patients and methods This was a 10-week ( 8-week active treatment/2-week post-treatment ) r and omized , double-blind , placebo- and active-controlled study ( D1448C00004 ) . Patients received quetiapine XR 150 mg/day , escitalopram 10 mg/day , or placebo ; patients with an inadequate response ( < 20 % improvement in Montgomery – Åsberg Depression Rating Scale [ MADRS ] total score ) at week two received double-dose treatment . The primary end point was week eight change from r and omization in MADRS total score . Secondary end points included MADRS response ( ≥50 % improvement ) and remission ( score ≤8 ) ; Hamilton Rating Scale for Depression total and item 1 ; Hamilton Rating Scale for Anxiety total , psychic , and somatic ; Clinical Global Impressions – Severity of Illness total ; Pittsburgh Sleep Quality Index ( PSQI ) global ; and Quality of Life Enjoyment and Satisfaction Question naire – Short Form percentage maximum total scores . Tolerability was assessed throughout . Results A total of 471 patients was r and omized . No significant improvements in MADRS total score were observed at week eight ( last observation carried forward ) with either active treatment ( quetiapine XR , −17.21 [ P=0.174 ] ; escitalopram , −16.73 [ P=0.346 ] ) versus placebo ( −15.61 ) . There were no significant differences in secondary end points versus placebo , with the exception of week-eight change in PSQI global score ( quetiapine XR , −4.96 [ P<0.01 ] versus placebo , −3.37 ) . Mixed-model repeated- measures analysis of observed-case data suggested that the primary analysis may not be robust . Most commonly reported adverse events included dry mouth , somnolence , and dizziness for quetiapine XR , and headache and nausea for escitalopram . Conclusion In this study , neither quetiapine XR ( 150/300 mg/day ) nor escitalopram ( 10/20 mg/day ) showed significant separation from placebo . Both compounds have been shown previously to be effective in the treatment of MDD ; possible reasons for this failed study are discussed . Quetiapine XR was generally well tolerated , with a profile similar to that reported previously OBJECTIVE The authors evaluated the efficacy and safety of lurasidone in the treatment of patients with major depressive episodes associated with bipolar I disorder . METHOD Patients were r and omly assigned to receive double-blind treatment with lurasidone ( 20 - 60 mg/day [ N=166 ] or 80 - 120 mg/day [ N=169 ] ) or placebo ( N=170 ) for 6 weeks . Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale ( MADRS ) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness ( CGI-BP ) , respectively . RESULTS Lurasidone treatment significantly reduced mean MADRS total scores at week 6 for both the 20 - 60 mg/day group ( -15.4 ; effect size=0.51 ) and the 80 - 120 mg/day group ( -15.4 ; effect size=0.51 ) compared with placebo ( -10.7 ) . Similarly , lurasidone treatment result ed in significantly greater endpoint reduction in CGI-BP depression severity scores for both the 20 - 60 mg/day group ( -1.8 ; effect size=0.61 ) and the 80 - 120 mg/day group ( -1.7 ; effect size=0.50 ) compared with placebo ( -1.1 ) . Both lurasidone groups also experienced significant improvements compared with placebo in anxiety symptoms and in patient-reported measures of quality of life and functional impairment . Discontinuation rates due to adverse events were similar in the 20 - 60 mg/day ( 6.6 % ) , 80 - 120 mg/day ( 5.9 % ) , and placebo ( 6.5 % ) groups . The most frequent adverse events associated with lurasidone were nausea , headache , akathisia , and somnolence . Minimal changes in weight , lipids , and measures of glycemic control were observed with lurasidone . CONCLUSION Monotherapy with lurasidone in the dosage range of 20 - 120 mg/day significantly reduced depressive symptoms in patients with bipolar I depression . Lurasidone was well tolerated , with few changes in weight or metabolic parameters OBJECTIVE To evaluate aripiprazole once-monthly ( AOM ) , a long-acting injectable suspension of aripiprazole , as acute treatment in patients with schizophrenia ( DSM-IV-TR ) . METHOD Adults experiencing an acute psychotic episode were r and omized to 12 weeks of double-blind treatment with AOM 400 mg or placebo ( October 2012-August 2013 ) . The primary efficacy outcome was change from baseline to endpoint ( week 10 ) in Positive and Negative Syndrome Scale ( PANSS ) total score . The key secondary efficacy outcome was change from baseline in Clinical Global Impressions-Severity of Illness scale ( CGI-S ) score . Secondary efficacy outcomes included change from baseline in PANSS positive and negative subscale and Personal and Social Performance Scale ( PSP ) scores . The study took place from October 2012 through August 2013 . RESULTS Patients ( N = 340 ; 79 % male , 66 % black ) were r and omized to AOM ( n = 168 ) or placebo ( n = 172 ) . Least squares ( LS ) mean change from baseline to endpoint ( week 10 ) favored AOM versus placebo in PANSS total ( treatment difference , -15.1 [ 95 % CI , -19.4 to -10.8 ] ; P < .0001 ) and CGI-S ( treatment difference , -0.8 [ 95 % CI , -1.1 to -0.6 ] ; P < .0001 ) scores , as it did at all other timepoints through 12 weeks ( all P ≤ .0005 ) . LS mean change from baseline in PANSS positive and negative subscale and PSP scores favored AOM versus placebo ( P < .0001 ) . Common ( > 10 % ) treatment-emergent adverse events ( AOM vs. placebo ) were increased weight ( 16.8 % vs 7.0 % ) , headache ( 14.4 % vs. 16.3 % ) , and akathisia ( 11.4 % vs 3.5 % ) . CONCLUSIONS Symptoms and functioning improved with AOM 400 mg versus placebo in patients with acute schizophrenia , with acceptable safety and tolerability . These data suggest that AOM 400 mg is a viable treatment option for patients experiencing an acute schizophrenia episode . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01663532 OBJECTIVE The efficacy , safety , and tolerability of brexpiprazole and placebo were compared in adults with acute schizophrenia . METHOD This was a multicenter , r and omized , double-blind , placebo-controlled study . Patients with schizophrenia experiencing an acute exacerbation were r and omly assigned to daily brexpiprazole at a dosage of 0.25 , 2 , or 4 mg or placebo ( 1:2:2:2 ) for 6 weeks . Outcomes included change from baseline to week 6 in Positive and Negative Syndrome Scale ( PANSS ) total score ( primary endpoint measure ) , Clinical Global Impressions Scale ( CGI ) severity score ( key secondary endpoint measure ) , and other efficacy and tolerability measures . RESULTS The baseline overall mean PANSS total score was 95.2 , and the CGI severity score was 4.9 . Study completion rates were 62.2 % , 68.1 % , and 67.2 % for patients in the 0.25- , 2- , and 4-mg brexpiprazole groups , respectively , versus 59.2 % in the placebo group . At week 6 , compared with placebo , brexpiprazole dosages of 2 and 4 mg produced statistically significantly greater reductions in PANSS total score ( treatment differences : -8.72 and -7.64 , respectively ) and CGI severity score ( treatment differences : -0.33 and -0.38 ) . The most common treatment-emergent adverse event for brexpiprazole was akathisia ( 2 mg : 4.4 % ; 4 mg : 7.2 % ; placebo : 2.2 % ) . Weight gain with brexpiprazole was moderate ( 1.45 and 1.28 kg for 2 and 4 mg , respectively , versus 0.42 kg for placebo at week 6 ) . There were no clinical ly or statistically significant changes from baseline in lipid and glucose levels and extrapyramidal symptom ratings . CONCLUSIONS Brexpiprazole at dosages of 2 and 4 mg/day demonstrated statistically significant efficacy compared with placebo and good tolerability for patients with an acute schizophrenia exacerbation The aim of this study was to evaluate the short-term efficacy and safety of lurasidone in treating irritability associated with autistic disorder . In this multicenter trial , out patients age 6–17 years who met DSM-IV-TR criteria for autistic disorder , and who demonstrated irritability , agitation , and /or self-injurious behaviors were r and omized to 6 weeks of double-blind treatment with lurasidone 20 mg/day ( N = 50 ) , 60 mg/day ( N = 49 ) , or placebo ( N = 51 ) . Efficacy measures included the Aberrant Behavior Checklist Irritability subscale ( ABC-I , the primary endpoint ) and the Clinical Global Impressions , Improvement ( CGI-I ) scale , and were analyzed using a likelihood-based mixed model for repeated measures . Least squares ( LS ) mean ( st and ard error [ SE ] ) improvement from baseline to Week 6 in the ABC-I was not significantly different for lurasidone 20 mg/day ( −8.8 [ 1.5 ] ) and lurasidone 60 mg/day ( −9.4 [ 1.4 ] ) versus placebo ( −7.5 [ 1.5 ] ; p = 0.55 and 0.36 , respectively ) . CGI-I scores showed significantly greater LS mean [ SE ] improvement at Week 6 for lurasidone 20 mg/day versus placebo ( 2.8 [ 0.2 ] vs. 3.4 [ 0.2 ] ; p = 0.035 ) but not for lurasidone 60 mg/day ( 3.1 [ 0.2 ] ; p = 0.27 ) . Discontinuation rates due to adverse events were : lurasidone 20 mg/day , 4.1 % ; 60 mg/day , 3.9 % ; and placebo , 8.2 % . Adverse events with an incidence ≥10 % ( lurasidone combined , placebo ) included vomiting ( 18.0 , 4.1 % ) and somnolence ( 12.0 , 4.1 % ) . Modest changes were observed in weight and selected metabolic parameters . In this study , once-daily , fixed doses of 20 and 60 mg/day of lurasidone were not demonstrated to be efficacious compared to placebo for the short-term treatment of children and adolescents with moderate-to-severe irritability associated with autistic disorder AIMS Morbidity and mortality from drug overdose has decreased over three decades . This is credited to safer drugs and therefore better outcomes in overdose . We aim ed to investigate changing prescriptions of antipsychotic medications and associated changes in antipsychotic overdoses over a 26-year period . METHODS All antipsychotic poisoning presentations to a tertiary referral toxicology unit between 1987 and 2012 were review ed . Data were collected prospect ively on demographics , ingestion information , clinical effects , complications and treatment . Rates of antipsychotic drug use in Australia were obtained from Australian government publications for 1990 - 2011 and linked to overdose admissions by postcode . RESULTS There were 3180 antipsychotic overdoses : 1235 first generation antipsychotics , 1695 ' atypical ' second generation antipsychotics and 250 lithium overdoses . Over 26 years , antipsychotic overdoses increased 1.8-fold , with first generation antipsychotics decreasing to one-fifth of their peak ( ≈80/year to 16 ) and second generation antipsychotics increasing to double this ( ≈160/year ) , olanzapine and quetiapine accounting for 78 % . All antipsychotic overdoses had a median length of stay of 18.6 h , 15.7 % admitted to intensive care unit , 10.4 % ventilated and 0.13 % died in hospital , which was the same for first generation compared to second generation antipsychotics . There was a 2.3-fold increase in anti Output:	The results support previous findings that weight-gain occurs quickly .
MS21649	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: 9083 Background : Teva 's CG-10639 is a long-acting recombinant human albumin-human granulocyte-colony stimulating factor under investigation to prevent chemotherapy-induced neutropenia . Similar to pegfilgrastim ( PEGF ) , CG-10639 stimulates neutrophil and hematopoietic stem cell mobilization from bone marrow to peripheral blood . No clinical ly relevant immunogenicity with CG-10639 has been observed to date . The main objective of this study was to evaluate the safety and effectiveness of CG-10639 versus PEGF in breast cancer patients ( BCA pts ) receiving myelosuppressive therapy . METHODS This phase II/III study was a r and omized , multi-center , active controlled trial in 334 BCA pts receiving doxorubicin/docetaxel ( DOX/DOC ) . The study included a pilot dose escalation phase to identify two CG-10639 doses with similar effects to PEGF ( 6 mg ) , and a main phase powered for efficacy ( non-inferiority ) . During the pilot phase , patients were r and omized to receive CG-10639 30 mg or PEGF one day after DOX/DOC followed by additional cohorts receiving CG-10639 40 mg , 50 mg . The main phase of the study used a r and omized , 3-arm parallel design comparing two doses of CG-10639 and PEGF following DOX 60mg/m2 and DOC 75mg/m2 IV on day 1 for up to four 21-day cycles . The primary endpoint was the duration of severe neutropenia ( DSN ) during cycle 1 in days ( d ) . RESULTS In the pilot phase ( n=78 ) DSN , secondary efficacy parameters and safety were similar across all treatments . CG-10639 40 mg and 50 mg doses were selected for further investigation . In the main phase ( n=256 ) , there were no statistically significant differences in mean DSN between CG-10639 40 mg ( 1.0d ) , CG-10639 50 mg ( 1.3d ) , and PEGF ( 1.2d ) in Cycle 1 . In each cycle , efficacy was comparable based on ANC nadir and recovery , the incidence and duration of Grade 3 or 4 neutropenia , and the incidence of febrile neutropenia . The type and frequency of treatment emergent AEs were similar across treatment groups . CONCLUSIONS These results support the conclusion that CG-10639 is non-inferior to PEGF based on mean DSN in BCA pts receiving myelosuppressive therapy . The overall safety profile was similar for CG-10639 and PEGF . A phase III , confirmatory study comparing CG-10639 40 mg to PEGF 6 mg is underway BACKGROUND Colony-stimulating factors ( CSFs ) significantly decrease the risk of febrile neutropenia ( FN ) , a common complication of myelosuppressive chemotherapy . Pegfilgrastim ( 6 mg ) , introduced in 2002 , has a sustained duration of action , with a single dose comparable in efficacy to daily injections of filgrastim ( 5 g per kg per day ) for 10 to 11 days ; both agents should be initiated 24 hours after completing chemotherapy . OBJECTIVES To ( 1 ) describe the use of pegfilgrastim and filgrastim in oncology practice s throughout the United States and ( 2 ) compare their effectiveness in actual practice as measured by the outcome of febrile neutropenia in patients who received chemotherapy regimens administered every 3 to 4 weeks for breast , lung , ovarian , colon cancer , or lymphoma and who received a CSF prior to developing FN . METHODS Data were retrospectively obtained from the medical records of a cohort of adult patients aged 18 years or older treated in 99 community oncology practice s in the United States in 2001 and 2003 . Eligible patients were treated with chemotherapy every 3 to 4 weeks for breast , lung , ovarian , colon cancer , or lymphoma and were users of filgrastim in 2001 ( prior to the U.S. Food and Drug Administration approval of pegfilgrastim in January 2002 ) or users of either filgrastim or pegfilgrastim or both CSF agents in 2003 . RESULTS Pegfilgrastim was initiated , on average , 2.4 days ( SD + /-3.2 ) after chemotherapy in the first cycle of use and 1.9 ( + /-3.0 ) days in subsequent cycles of use . In contrast , filgrastim was started on average 7.7 ( + /-6.5 ) days and 4.9 ( 4.6 ) days after chemotherapy in the first and subsequent cycles of use in 2001 , increasing to 9.6 ( + /-6.2 ) and 6.4 ( + /-6.4 ) days in 2003 . In the first cycle of CSF use , filgrastim was administered for an average of 5.2 ( + /-3.5 ) days to 583 patients in 2001 and 3.7 ( + /-2.8 ) days to 868 patients in 2003 ( P < 0.001 ) . Among patients who received more than 1 cycle of filgrastim ( n = 457 in 2001 and n = 489 in 2003 ; 78.4 % and 56.3 % of filgrastim users , respectively ) , the mean days of filgrastim administered in subsequent cycles was 6.0 ( + /-3.5 ) in 2001 and 4.6 ( + /-3.2 ) in 2003 . Pegfilgrastim was administered as a single dose per chemotherapy course to 1,412 patients in 2003 . Patients who received pegfilgrastim were more likely to have at least 1 myelosuppressive drug ( 74.8 % ) in the regimen compared with patients who received filgrastim in 2003 ( 70.0 % , P = 0.013 ) , but a greater proportion of filgrastim patients in 2003 ( 19.4 % ) had advanced-stage disease compared with pegfilgrastim patients ( 14.8 % , P = 0.005 ) . More patients who received filgrastim in 2003 ( 36.2 % ) had a cancer other than breast cancer or non-Hodgkin 's lymphoma compared with those who received pegfilgrastim ( 29.5 % , P = 0.001 ) . A total of 94 of 1,451 patients ( 6.5 % ) who received filgrastim experienced FN compared with 67 of 1,412 patients ( 4.7 % ) for pegfilgrastim . The odds ratio of developing FN among patients who received filgrastim versus pegfilgrastim was 1.41 ( 95 % confidence interval , 1.02 - 1.96 ; P = 0.040 ) after adjusting for patient and chemotherapy regimen characteristics . CONCLUSION In this retrospective study of patients treated in 99 community oncology practice s , patients who received filgrastim often initiated treatment later than recommended and received fewer days per cycle than demonstrated to be effective in r and omized controlled trials . Pegfilgrastim was generally initiated earlier within the course of chemotherapy compared with filgrastim , and because of its sustained duration of action , only a single injection was required . In these patients treated with a heterogeneous group of chemotherapy regimens with a broad range of risk of FN , overall , an absolute 1.8 % increase in the incidence of developing FN was observed in patients who received filgrastim compared with patients who received pegfilgrastim , ( absolute rates of 6.5 % and 4.7 % , respectively ) BACKGROUND TAC ( docetaxel/doxorubicin/cyclophosphamide ) is associated with high incidences of grade 4 neutropenia and febrile neutropenia ( FN ) . This analysis compared the efficacies of four regimens for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC . PATIENTS AND METHODS Patients with stage T2-T4 primary breast cancer were scheduled to receive 6 - 8 cycles of TAC . Primary prophylaxis was : ciprofloxacin 500 mg orally twice daily on days 5 - 14 ( n = 253 patients ; 1478 cycles ) , daily granulocyte colony-stimulating factor ( G-CSF ) ( filgrastim 5 microg/kg/day or lenograstim 150 microg/m(2)/day ) on days 5 - 10 ( n = 377 ; 2400 cycles ) , pegfilgrastim 6 mg on day 2 ( n = 305 ; 1930 cycles ) , or pegfilgrastim plus ciprofloxacin ( n = 321 ; 1890 cycles ) . RESULTS Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN ( 5 % and 7 % versus 18 % and 22 % of patients ; all P < 0.001 ) , grade 4 neutropenia , and leukopenia . Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN ( P < 0.01 versus pegfilgrastim alone ) and fatal neutropenic events . CONCLUSION Ciprofloxacin alone , or daily G-CSF from day 5 - 10 ( as in common practice ) , provided suboptimal protection against FN and related toxic effects in patients receiving TAC . Pegfilgrastim was significantly more effective in this setting , especially if given with ciprofloxacin PURPOSE We evaluated the efficacy of pegfilgrastim to reduce the incidence of febrile neutropenia associated with docetaxel in breast cancer patients . PATIENTS AND METHODS Patients were r and omly assigned to either placebo or pegfilgrastim 6 mg subcutaneously on day 2 of each 21-day chemotherapy cycle of 100 mg/m(2 ) docetaxel . The primary end point was the percentage of patients developing febrile neutropenia ( defined as body temperature > /= 38.2 degrees C and neutrophil count < 0.5 x 10(9)/L on the same day of the fever or the day after ) . Secondary end points were incidence of hospitalizations associated with a diagnosis of febrile neutropenia , intravenous ( IV ) anti-infectives required for febrile neutropenia , and the ability to maintain planned chemotherapy dose on time . Patients with febrile neutropenia were converted to open-label pegfilgrastim in subsequent cycles . RESULTS Nine hundred twenty-eight patients received placebo ( n = 465 ) or pegfilgrastim ( n = 463 ) . Patients receiving pegfilgrastim , compared with patients receiving placebo , had a lower incidence of febrile neutropenia ( 1 % v 17 % , respectively ; P < .001 ) , febrile neutropenia-related hospitalization ( 1 % v 14 % , respectively ; P < .001 ) , and use of IV anti-infectives ( 2 % v 10 % , respectively ; P < .001 ) . The percentage of patients receiving the planned dose on time was similar between patients receiving pegfilgrastim and patients who initially received placebo ( 80 % and 78 % , respectively ) , as would be expected of the study design . Pegfilgrastim was generally well tolerated and safe , and the adverse events reported were typical of this patient population . CONCLUSION First and subsequent cycle use of pegfilgrastim with a moderately myelosuppressive chemotherapy regimen markedly reduced febrile neutropenia , febrile neutropenia-related hospitalizations , and IV anti-infective use Aim : Febrile neutropenia ( FN ) is a highly prevalent complication of chemotherapy , particularly in patients with non‐Hodgkin 's lymphoma . This study aim ed to compare the efficacy of filgrastim and pegfilgrastim in Asian lymphoma patients by evaluating the incidence of FN and associated complications Aim of the study PROFIL was a prospect i ve observational study conducted to investigate physicians ’ evaluation of febrile neutropenia ( FN ) risk and reasons for giving pegfilgrastim primary prophylaxis ( PP ) in routine clinical practice in Pol and . Material and methods Adult cancer patients treated with chemotherapy ( CT ) , assessed by investigators as having high overall FN risk , and who received pegfilgrastim in cycle 1 were enrolled between 03/2009 and 09/2010 . Investigators assessed FN risk of the CT regimen , individual risk factors , and overall FN risk , and were asked to provide the most important reasons for providing pegfilgrastim PP . Investigator-assessed CT FN risk was compared with guideline classification . Results Data were analysed from 1006 breast , ovarian , and lung cancer , and non-Hodgkin ( NHL ) and Hodgkin lymphoma ( HL ) patients . The most important reasons for using pegfilgrastim PP were high CT FN risk and advanced disease ; these were consistent across tumour types and treatment intent . The investigators generally assessed high CT FN risk in agreement with guideline classification . Febrile neutropenia occurred in 4 % of patients , most commonly in HL , NHL , and patients with advanced disease . Conclusions High CT FN risk and advanced Output:	Conclusions Pegfilgrastim reduced the incidence of FN and CIN compared with no prophylaxis . Most studies showed better efficacy and effectiveness for pegfilgrastim than filgrastim . Efficacy and safety profiles of lipegfilgrastim and balugrastim were similar to pegfilgrastim
MS21650	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Depression is associated with an increased risk of cardiovascular diseases ( CVD ) in vascular patients as well as in the general population . We investigated whether autonomic dysfunction could explain this relationship . Design The Finl and , Italy and The Netherl and s Elderly ( FINE ) Study is a prospect i ve cohort study . Methods Depressive symptoms were measured with the Zung Self-rating Depression Scale in 870 men , aged 70 - 90 years , free of CVD and diabetes in 1990 . Resting heart rate was determined from a 15 - 30-s resting electrocardiogram in The Netherl and s and Italy and as pulse rate in Finl and . In addition , in The Netherl and s , heart-rate variability ( HRV ) and QTc interval were determined . Results At baseline , depressive symptoms were associated with an increase in resting heart rate , and nonsignificantly with low HRV and prolonged QTc interval . After 10 years of follow-up , 233 ( 27 % ) men died from CVD . Prospect ively , an increase in resting heart rate with 1 SD was associated with an increased risk of cardiovascular mortality [ hazard ratio ( HR ) , 1.22 ; 95 % confidence interval ( CI ) , 1.08 - 1.38 ] . In addition , low HRV ( HR , 0.78 ; 95 % CI , 0.61 - 1.01 ) and prolonged QTc interval ( HR , 1.28 ; 95 % CI , 1.06 - 1.53 ) per SD were associated with cardiovascular mortality . The increased risk of depressive symptoms for cardiovascular mortality ( HR , 1.38 ; 95 % CI , 1.21 - 1.58 ) did not change after adjustments for several indicators of autonomic dysfunction . Conclusion This study suggests that mild depressive symptoms are associated with autonomic dysfunction in elderly men . The increased risk of cardiovascular mortality with increasing magnitude of depressive symptoms could , however , not be explained by autonomic dysfunction . Eur J Cardiovasc Prev Rehabil 14 : 796 - 802 © 2007 The European Society of PURPOSE To prospect ively evaluate if high- grade ( > or = 80 % luminal narrowing ) internal carotid artery stenosis is associated with depressive symptoms and if carotid artery stent placement ( CAS ) potentially improves depressive symptoms . MATERIAL S AND METHODS The study was approved by the local ethics committee , and informed consent was obtained from all subjects . One hundred forty-three patients ( 91 men , 52 women ; interquartile range , 63 - 76 years ) undergoing CAS because of asymptomatic high- grade ( > or = 80 % luminal narrowing ) carotid artery stenosis and 102 control subjects ( 64 men , 38 women ; interquartile range , 63 - 73 years ) with advanced peripheral artery disease and without carotid artery stenosis undergoing lower-limb percutaneous transluminal angioplasty were included . Substantial depressive symptoms ( defined as a Beck Depression Inventory score of 10 or higher ) were recorded at baseline and at 4 weeks ( follow-up ) after the percutaneous procedures . The chi2 test , Mann-Whitney U test , McNemar test , Wilcoxon rank sum test , and two-group t test were used to check for statistical significance . RESULTS A significantly higher prevalence of depressive symptoms was found in patients with carotid artery stenosis than in control subjects with peripheral artery disease at baseline ( 33.6 % vs 16.7 % , P = .003 ) . At follow-up , a significant reduction of depressive symptoms was found in patients who underwent CAS ( 33.6 % vs 9.8 % , P < .001 ) . The frequency of depressive symptoms remained unaffected in control subjects ( 16.7 % vs 13.0 % , P = .1 ) . CONCLUSION High- grade carotid artery stenosis is associated with depressive symptoms in patients with atherosclerosis . CAS seems to exert beneficial effects on the course of depressive symptoms in these patients CONTEXT Research on vascular depression has used 2 approaches to subtype late-life depression , based on executive dysfunction or white matter hyperintensity severity . OBJECTIVE To evaluate the relationship of neuropsychological performance and white matter hyperintensity with clinical response in late-life depression . DESIGN Two-site , prospect i ve , nonr and omized controlled trial . SETTING Outpatient clinics at Washington University and Duke University . PARTICIPANTS A total of 217 subjects aged 60 years or older met DSM-IV criteria for major depression , scored 20 or more on the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and received vascular risk factor scores , neuropsychological testing , and magnetic resonance imaging ; they were excluded for cognitive impairment or severe medical disorders . Fazekas rating was conducted to grade white matter hyperintensity lesions . Intervention Twelve weeks of sertraline treatment , titrated by clinical response . Main Outcome Measure Participants ' MADRS scores over time . RESULTS Baseline neuropsychological factor scores correlated negatively with baseline Fazekas scores . A mixed model examined effects of predictor variables on MADRS scores over time . Baseline episodic memory ( P = .002 ) , language ( P = .007 ) , working memory ( P = .01 ) , processing speed ( P < .001 ) , executive function factor scores ( P = .002 ) , and categorical Fazekas ratings ( P = .05 ) predicted MADRS scores , controlling for age , education , age of onset , and race . Controlling for baseline MADRS scores , these factors remained significant predictors of decrease in MADRS scores , except for working memory and Fazekas ratings . Thirty-three percent of subjects achieved remission ( MADRS < or = 7 ) . Remitters differed from nonremitters in baseline cognitive processing speed , executive function , language , episodic memory , and vascular risk factor scores . CONCLUSIONS Comprehensive neuropsychological function and white matter hyperintensity severity predicted MADRS scores prospect ively over a 12-week treatment course with selective serotonin reuptake inhibitors in late-life depression . Baseline neuropsychological function differentiated remitters from nonremitters and predicted time to remission in a proportional hazards model . Predictor variables correlated highly with vascular risk factor severity . These data support the vascular depression hypothesis and highlight the importance of linking subtypes based on neuropsychological function and white matter integrity . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00045773 Beneficial effects of repetitive transcranial magnetic stimulation ( rTMS ) were demonstrated by many controlled studies in major depression . Moreover , this promising and non invasive therapeutic tool seems to be better tolerated than electroconvulsive therapy CONTEXT The term vascular depression ( VD ) has been used to describe late-life depressive disorders in patients with clinical evidence of cerebrovascular disease . Preliminary data on poststroke depression suggest that repetitive transcranial magnetic stimulation ( rTMS ) might also be effective among patients with VD . OBJECTIVE To examine the efficacy and safety of rTMS to treat VD . DESIGN Prospect i ve , r and omized , sham-controlled study . SETTING University hospital . METHODS After discontinuation of antidepressant therapy , 92 patients with clinical ly defined VD were r and omly assigned to receive active or sham rTMS of the left dorsolateral prefrontal cortex . Approximately half of the patients met criteria for magnetic resonance imaging-defined VD . In experiment 1 , we administered a total cumulative dose ( TCD ) of 12 000 pulses ( TCD-12 K ) ; in experiment 2 , 18,000 pulses ( TCD-18 K ) . Sham stimulation was performed using a sham coil . RESULTS In experiment 1 , the sham group showed a 13.6 % decrease in the 17-item Hamilton Depression Rating Scale ( HAMD-17 ) scores compared with a 33.1 % decrease in the TCD-12 K group ( P = .04 ) . Response rates were 6.7 % in the sham group and 33.3 % in the active-stimulation group ( P = .08 ) ; remission rates were 6.7 % and 13.3 % , respectively ( P = .50 ) . In experiment 2 , the sham group showed a 17.5 % decrease in the 17-item Hamilton Depression Rating Scale scores compared with a 42.4 % decrease observed in the TCD-18 K group ( P < .001 ) . Response rates were 6.9 % in the sham group and 39.4 % in the active-stimulation group ( P = .003 ) ; remission rates were 3.5 % and 27.3 % , respectively ( P = .01 ) . Response rates to rTMS were negatively correlated with age and positively correlated with higher frontal gray matter volumes . CONCLUSIONS To our knowledge , this is the first controlled trial that demonstrates the efficacy of rTMS among geriatric patients with VD . Older age and smaller frontal gray matter volumes were associated with a poorer response to rTMS OBJECTIVES The authors previously reported that repetitive transcranial magnetic stimulation ( rTMS ) produced a response rate of 39.4 % among 62 patients with treatment resistant vascular depression . This study was undertaken to assess the outcome of continuation therapy to prevent relapse among these patients during 9 weeks after completion of rTMS . DESIGN Patients were r and omly assigned to 18,000 pulses of rTMS given over 3 weeks or sham treatment using double blind methods . After rTMS , all patients were given 20 mg/day of citalopram for 9 weeks and reevaluated at 3 , 6 , and 9 weeks . SETTING Outpatient continuation treatment trial . PARTICIPANTS Patients with vascular depression ( N = 62 ) , as determined by magnetic resonance imaging hyperintensities and three or more clinical risk factors for vascular disease without other major medical illness , were recruited . They had onset of major depression after age 50 and failed at least one trial of antidepressants . INTERVENTION After rTMS or sham treatment , all treatment responders were given citalopram for 9 weeks . RESULTS Among the 33 patients who were given rTMS , 13 responded ( i.e. , > 50 % decline in Hamilton Depression Scale score ) . Of these 13 , all completed the 9 weeks of continuation treatment . There were nine patients who continued to be responders and four who had a relapse of depression . CONCLUSION More effective methods are needed to treat elderly patients with treatment resistant vascular depression and to prevent relapse among treatment responders BACKGROUND Vascular depression has been proposed as a unique diagnostic subtype in late life , yet no study has evaluated whether the specified clinical features associated with the illness are jointly indicative of an underlying diagnostic class . METHODS We applied latent class analysis to two independent clinical sample s : the prospect i ve , cohort design , Neurocognitive Outcomes of Depression in the Elderly ( NCODE ) study and the 8-week , multicenter , double blind , placebo-controlled Old-Old study . RESULTS A two-class model consisting of vascular and nonvascular depressed patients provided an excellent fit to the data in both studies , chi(2)(6 ) = 2.02 , p = .90 in the NCODE study and chi(2)(6 ) = 7.024 , p = .32 in the Old-Old study . Although all of the proposed features of vascular depression were useful in identifying the illness , deep white matter lesion burden emerged with perfect sensitivity ( 1.00 ) and near-perfect specificity ( .95 ) , making it the only indicator necessary to determine class membership . CONCLUSIONS These findings , replicated across two independent clinical sample s , provide the first support for the internal validity of vascular depression as a subtype of late-life depression BACKGROUND ' Vascular depression ' may be caused by cerebrovascular disease . Calcium channel blockers , which are putative treatments for cerebrovascular disease , might be expected to improve depression reduction and to prevent recurrence of depression in this patient population . This clinical trial was design ed to test these hypotheses . DESIGN This was a controlled , double blind , r and omized clinical trial in which 84 patients with vascular depression ( Alexopoulos criteria ) were treated with antidepressants at st and ard doses . Patients were also r and omized to nimodipine ( n = 40 ) or an inactive comparator , vitamin C ( n = 44 ) . Treatment outcomes were assessed using the Hamilton depression rating scale ( HDRS ) regularly up to 300 days after treatment initiation . RESULTS As expected , depression reduction was successful in most patients . In addition , those treated with nimodipine plus an antidepressant had greater improvements in depression overall in repeated measures ANCOVA ( F(1,81 ) = 8.64 , p = 0.004 ) . As well a greater proportion of nimodipine-treated participants ( 45 versus 25 % ) exhibited a full remission ( HDRS < or = 10 ) ( chi(2)(df , 1 ) = 3.71 , p = 0.054 ) . Among those experiencing a substantial response in the first 60 days ( 50 % reduction in Output:	Efficacy trials suggested that nimodipine , transcranial magnetic stimulation , carotid stent placement , and citalopram were effective for VaD. Exploratory studies suggested that white-matter hyperintensities and global vascular risk are predictors of poor response . Although the low quality of the studies hinders the findings ' generalization , studies of higher validity support the VaD concept for interventions .
MS21651	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Despite years of research and hundreds of reports on tumor markers in oncology , the number of markers that have emerged as clinical ly useful is pitifully small . Often , initially reported studies of a marker show great promise , but subsequent studies on the same or related markers yield inconsistent conclusions or st and in direct contradiction to the promising results . It is imperative that we attempt to underst and the reasons that multiple studies of the same marker lead to differing conclusions . A variety of method ologic problems have been cited to explain these discrepancies . Unfortunately , many tumor marker studies have not been reported in a rigorous fashion , and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results . The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer ( NCI-EORTC ) First International Meeting on Cancer Diagnostics in 2000 . As for the successful CONSORT initiative for r and omized trials and for the STARD statement for diagnostic studies , we suggest guidelines to provide relevant information about the study design , preplanned hypotheses , patient and specimen characteristics , assay methods , and statistical analysis methods . In addition , the guidelines suggest helpful presentations of data and important elements to include in discussion s. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and underst and the context in which the conclusions apply Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items Significance Whole-exome sequencing ( WES ) is gradually being optimized to identify mutations in increasing proportions of the protein-coding exome , but whole-genome sequencing ( WGS ) is becoming an attractive alternative . WGS is currently more expensive than WES , but its cost should decrease more rapidly than that of WES . We compared WES and WGS on six unrelated individuals . The distribution of quality parameters for single-nucleotide variants ( SNVs ) and insertions/deletions ( indels ) was more uniform for WGS than for WES . The vast majority of SNVs and indels were identified by both techniques , but an estimated 650 high- quality coding SNVs ( ∼3 % of coding variants ) were detected by WGS and missed by WES . WGS is therefore slightly more efficient than WES for detecting mutations in the targeted exome . We compared whole-exome sequencing ( WES ) and whole-genome sequencing ( WGS ) in six unrelated individuals . In the regions targeted by WES capture ( 81.5 % of the consensus coding genome ) , the mean numbers of single-nucleotide variants ( SNVs ) and small insertions/deletions ( indels ) detected per sample were 84,192 and 13,325 , respectively , for WES , and 84,968 and 12,702 , respectively , for WGS . For both SNVs and indels , the distributions of coverage depth , genotype quality , and minor read ratio were more uniform for WGS than for WES . After filtering , a mean of 74,398 ( 95.3 % ) high- quality ( HQ ) SNVs and 9,033 ( 70.6 % ) HQ indels were called by both platforms . A mean of 105 coding HQ SNVs and 32 indels was identified exclusively by WES whereas 692 HQ SNVs and 105 indels were identified exclusively by WGS . We Sanger-sequenced a r and om selection of these exclusive variants . For SNVs , the proportion of false-positive variants was higher for WES ( 78 % ) than for WGS ( 17 % ) . The estimated mean number of real coding SNVs ( 656 variants , ∼3 % of all coding HQ SNVs ) identified by WGS and missed by WES was greater than the number of SNVs identified by WES and missed by WGS ( 26 variants ) . For indels , the proportions of false-positive variants were similar for WES ( 44 % ) and WGS ( 46 % ) . Finally , WES was not reliable for the detection of copy-number variations , almost all of which extended beyond the targeted regions . Although currently more expensive , WGS is more powerful than WES for detecting potential disease-causing mutations within WES regions , particularly those due to SNVs BACKGROUND Data from observational studies suggest that body mass index ( BMI ) is causally related to esophageal adenocarcinoma ( EAC ) and its precursor , Barrett 's esophagus ( BE ) . However , the relationships may be affected by bias and confounding . METHODS We used data from the Barrett 's and Esophageal Adenocarcinoma Genetic Susceptibility Study : 999 patients with EAC , 2061 patients with BE , and 2169 population controls . We applied the two-stage control function instrumental variable method of the Mendelian r and omization approach to estimate the unbiased , unconfounded effect of BMI on risk of EAC and BE . This was performed using a genetic risk score , derived from 29 genetic variants shown to be associated with BMI , as an instrument for lifetime BMI . A higher score indicates propensity to obesity . All tests were two-sided . RESULTS The genetic risk score was not associated with potential confounders , including gastroesophageal reflux symptoms and smoking . In the instrumental variable analyses ( IV ) , EAC risk increased by 16 % ( IV-odds ratio [ OR ] = 1.16 , 95 % Output:	Conclusions Patients with OAC and TP53 gene mutations have reduced overall survival compared with patients without these mutations , and this effect is independent of tumour stage
MS21652	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract The clinical application of sentinel node biopsies in early gastric cancer is still controversial even though it appears promising . This study was conducted as a prerequisite quality control for surgical st and ardization of laparoscopic sentinel basin dissection ( SBD ) prior to the initiation of a phase III trial . Laparoscopic SBD was performed in patients with preoperative stage T1 - 2N0 and tumor size < 4 cm in diameter . Intraoperative endoscopic submucosal injection of a st and ardized dual tracer was administered . All retrieved sentinel basin nodes ( SBN ) were investigated with intraoperative frozen hematoxylin and eosin ( H&E ) staining . A strict checklist consisting of 7 essential steps was followed during laparoscopic SBD as the quality control study for a phase III trial . Completion of all essential steps in the checklist for 10 cases was used to define a qualified institution . Seven institutions participated and 112 patients were enrolled in this study . However , 4 patients were excluded owing to screening failure . The mean number of cases required for institutional qualification was 15 cases ( range , 13–20 cases ) . Sentinel basins ( SB ) were detected and dissected in 100 of the 108 patients ( 92.6 % ) ; the median number of SB and SBN was 2 and 7 , respectively . Lymph node metastases were detected in 10 patients by postoperative permanent H&E staining and they were detected by SBD in all 10 patients . Frozen results of SBN were compatible with permanent staining reports . Laparoscopic SBD is feasible and demonstrated improved sensitivity in detecting metastatic lymph nodes compared to the previous study . A future phase III r and omized trial comparing laparoscopic SBD with organ-preserving gastrectomy and laparoscopic st and ard gastrectomy seems promising for qualified institutions AIM To investigate feasibility and accuracy of near-infrared fluorescence imaging using indocyanine green : nanocolloid for sentinel lymph node ( SLN ) detection in gastric cancer . METHODS A prospect i ve , single-institution , phase I feasibility trial was conducted . Patients suffering from gastric cancer and planned for gastrectomy were included . During surgery , a subserosal injection of 1.6 mL ICG : Nanocoll was administered around the tumor . NIR fluorescence imaging of the abdominal cavity was performed using the Mini-FLARE ™ NIR fluorescence imaging system . Lymphatic pathways and SLNs were visualized . Of every detected SLN , the corresponding lymph node station , signal-to- background ratio and histopathological diagnosis was determined . Patients underwent st and ard-of-care gastrectomy . Detected SLNs outside the st and ard dissection planes were also resected and evaluated . RESULTS Twenty-six patients were enrolled . Four patients were excluded because distant metastases were found during surgery or due to technical failure of the injection . In 21 of the remaining 22 patients , at least 1 SLN was detected by NIR Fluorescence imaging ( mean 3.1 SLNs ; range 1 - 6 ) . In 8 of the 21 patients , tumor-positive LNs were found . Overall accuracy of the technique was 90 % ( 70%-99 % ; 95%CI ) , which decreased by higher pT-stage ( 100 % , 100 % , 100 % , 90 % , 0 % for respectively Tx , T1 , T2 , T3 , T4 tumors ) . All NIR-negative SLNs were completely effaced by tumor . Mean fluorescence signal-to- background ratio of SLNs was 4.4 ( range 1.4 - 19.8 ) . In 8 of the 21 patients , SLNs outside the st and ard resection plane were identified , that contained malignant cells in 2 patients . CONCLUSION This study shows successful use of ICG : Nanocoll as lymphatic tracer for SLN detection in gastric cancer . Moreover , tumor-containing LNs outside the st and ard dissection planes were identified Background Prospect i ve multicenter trials have shown the feasibility of sentinel node ( SN ) navigation surgery using a dual tracer of dye and radioisotope for early gastric cancer . However , comparable trials using the indocyanine green ( ICG ) and the infrared ray laparoscopic system ( IRLS ) have not been reported . On the basis of our cohort studies , we assumed that the ICG imaging with the IRLS is as effective as the dual tracer in detecting SNs . Therefore , we conducted a prospect i ve multicenter trial to assess the effectiveness and generalizability of the infrared ICG technique in patients with early gastric cancer . Patients and methods Patients with previously untreated cT1 gastric adenocarcinomas less than 4 cm in gross diameter were eligible for inclusion in this study . SN mapping was performed by using ICG combined with IRLS technique . Following biopsy of the identified SNs , D2 or modified D2 laparoscopic gastrectomy was performed according to the current Japanese Gastric Cancer Association guidelines . Results Among the 47 patients who gave written informed consent , 44 were eligible from the surgical findings , for whom SN biopsy was performed . The detection rate of the lymphatic basin by the ICG with IRLS was 100 % ( 44/44 ) . The accuracy was also 100 % ( 7/7 ) for detecting metastatic lymph node , which was verified on the permanent pathologic examination . Following the median follow-up of 114 months ( range , 60 to 120 months ) , no recurrence ( 0/40 ) was observed . Although the number of patients was unequally distributed among the hospitals participating in the trial , the detection rates of SNs in low-volume hospitals were comparable to those in high-volume hospitals . Consequently , there was no learning curve in this trial . Conclusion The infrared ICG imaging accurately detected the lymphatic basin and SNs with occult metastasis in SN-navigated gastrectomy for gastric cancer . This method was feasible even for low-volume surgeons and hospitals More than ten years have passed since the sentinel node ( SN ) concept for gastric cancer surgery was first discussed . Less invasive modified surgical approaches based on the SN concept have already been put into practice for malignant melanoma and breast cancer , however the SN concept is not yet placed in a st and ard position in gastric cancer surgery even after two multi-institutional prospect i ve clinical trials , the Japan Clinical Oncology Group trial ( JCOG0302 ) and the Japanese Society for Sentinel Node Navigation Surgery ( SNNS ) trial . What is the problem in the clinical application of the SN concept to gastric cancer surgery ? There is no doubt that we need reliable indicator(s ) to determine with certainty the absence of metastasis in the lymph nodes in order to avoid unnecessary lymphadenectomy . There are several matters of debate in performing the actual procedure , such as the type of tracer , the site of injection , how to detect and harvest , how to detect metastases of SNs , and learning period . These issues have to be addressed further to establish the most suitable procedure . Novel technologies such as indocyanine green ( ICG ) fluorescence imaging and one-step nucleic acid amplification ( OSNA ) may overcome the current difficulties . Once we know what the problems are and how to tackle them , we can pursue the goal Background Along with the marked increase in early gastric cancer ( EGC ) in the Eastern countries , there has been an effort to adopt the sentinel node concept in EGC to preserve gastric function and reduce the occurrence of postoperative complications . Based on promising results from a previous quality control study , this prospect i ve multicenter r and omized controlled phase III clinical trial aims to eluci date the oncologic safety of laparoscopic stomach-preserving surgery with sentinel basin dissection ( SBD ) compared to a st and ard laparoscopic gastrectomy . Methods / Design This trial is an investigator-initiated , open-label , multicenter r and omized controlled phase III trial with a non-inferiority design . Patients diagnosed with a single lesion of clinical stage T1N0M0 gastric adenocarcinoma , with a diameter of 3 cm or less are eligible for the present study . A total of 580 patients ( 290 per group ) will be r and omized to either laparoscopic stomach-preserving surgery with SBD or st and ard surgery . The primary end-point is 3-year disease-free survival ( DFS ) and the secondary endpoints include postoperative morbidity and mortality , quality of life , 5-year DFS , and overall survival . Qualified investigators who completed the prior quality control study are exclusively allowed to participate in this phase III clinical trial . Discussion The proposed trial is expected to verify whether laparoscopic stomach-preserving surgery with SBD achieves similar oncologic outcomes and improved quality of life compared to a st and ard gastrectomy in EGC patients .Trial registration This study was registered at the NIH Clinical Trial.gov data base ( NCT01804998 ) on March 4th , 2013 BACKGROUND Examination of at least 16 lymph nodes ( LNs ) has been traditionally recommended during gastric adenocarcinoma resection to optimize staging , but the impact of this strategy on survival is uncertain . Because recent r and omized trials have demonstrated a therapeutic benefit from extended lymphadenectomy , we sought to investigate the impact of the number of LNs removed on prognosis after gastric adenocarcinoma resection . STUDY DESIGN We analyzed patients who underwent gastrectomy for gastric adenocarcinoma from 2000 to 2012 , at 7 US academic institutions . Patients with M1 disease or R2 resections were excluded . Disease-specific survival ( DSS ) was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses . RESULTS Of 742 patients , 257 ( 35 % ) had 7 to 15 LNs removed and 485 ( 65 % ) had ≥16 LNs removed . Disease-specific survival was not significantly longer after removal of ≥16 vs 7 to 15 LNs ( 10-year survival , 55 % vs 47 % , respectively ; p = 0.53 ) for the entire cohort , but was significantly improved in the subset of patients with stage IA to IIIA ( 10-year survival , 74 % vs 57 % , respectively ; p = 0.018 ) or N0 - 2 disease ( 72 % vs 55 % , respectively ; p = 0.023 ) . Similarly , for patients who were classified to more likely be " true N0 - 2 , " based on frequentist analysis incorporating both the number of positive and of total LNs removed , the hazard ratio for disease-related death ( adjusted for T stage , R status , grade , receipt of neoadjuvant and adjuvant therapy , and institution ) significantly decreased as the number of LNs removed increased . CONCLUSIONS The number of LNs removed during gastrectomy for adenocarcinoma appears itself to have prognostic implication s for long-term survival BACKGROUND The survival benefit and morbidity after nodal dissection for gastric cancer remains controversial . We aim ed to do a single-institution r and omised trial to compare D1 ( ie , level 1 ) lymphadenectomy with that of D3 ( ie , levels 1 , 2 , and 3 ) dissection for gastric cancer in terms of overall survival and disease-free survival . METHODS From Oct 7 , 1993 , to Aug 12 , 1999 , 335 patients were registered . 221 patients were eligible , 110 of whom were r and omly assigned D1 surgery and 111 of whom were r and omly assigned D3 surgery , both with curative intent . Three participating surgeons had done at least 25 independent D3 dissections before the start of the trial , and every procedure was verified by pathological analyses . The primary endpoints were 5-year overall survival and 5-year disease-free survival . We also analysed risk of recurrence . Main analyses were done by intention to treat . This trial is registered at the US National Institute of Health website . FINDINGS Median follow-up for the 110 ( 50 % ) survivors was 94.5 months ( range 62.9 - 135.1 ) . Overall 5-year survival was significantly higher in patients assigned D3 surgery than in those assigned D1 surgery ( 59.5 % [ 95 % CI 50.3 - 68.7 ] vs 53.6 % [ 44.2 - 63.0 ] ; difference beteween groups 5.9 % [ -7.3 to 19.1 ] , log-rank p=0.041 ) . 215 patients who had R0 resection ( ie , no microscopic evidence of residual disease ) had recurrence at 5 years of 50.6 % [ 41.1 - 60.2 ] for D1 surgery and 40.3 % [ 30.9 - 49.7 ] for D3 surgery ( difference between groups 10.3 % [ -3.2 to 23.7 ] , log-rank p=0.197 ) . INTERPRETATION D3 nodal dissection , compared with that of D1 , offers a survival benefit for patients with gastric cancer when done by well trained , experienced surgeons BACKGROUND Historical data and recent studies show that st and ardised extended ( D2 ) lymphadenectomy leads to Output:	IREE had improved diagnostic odds ratio , sensitivity , and identification rate compared to NIFI . Conclusions We found encouraging results regarding the accuracy , diagnostic odds ratio , and specificity of the test . The sensitivity was not optimal but may be improved by a strict protocol to augment the technique .
MS21653	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The oxygen uptake efficiency slope ( OUES ) is a submaximal index incorporating cardiovascular , peripheral , and pulmonary factors that determine the ventilatory response to exercise . The purpose of this study was to evaluate the effects of continuous exercise training and interval exercise training on the OUES in patients with coronary artery disease . Thirty-five patients ( 59.3±1.8 years old ; 28 men , 7 women ) with coronary artery disease were r and omly divided into two groups : continuous exercise training ( n=18 ) and interval exercise training ( n=17 ) . All patients performed grade d exercise tests with respiratory gas analysis before and 3 months after the exercise-training program to determine ventilatory anaerobic threshold ( VAT ) , respiratory compensation point , and peak oxygen consumption ( peak VO2 ) . The OUES was assessed based on data from the second minute of exercise until exhaustion by calculating the slope of the linear relation between oxygen uptake and the logarithm of total ventilation . After the interventions , both groups showed increased aerobic fitness ( P<0.05 ) . In addition , both the continuous exercise and interval exercise training groups demonstrated an increase in OUES ( P<0.05 ) . Significant associations were observed in both groups : 1 ) continuous exercise training ( OUES and peak VO2 r=0.57 ; OUES and VO2 VAT r=0.57 ) ; 2 ) interval exercise training ( OUES and peak VO2 r=0.80 ; OUES and VO2 VAT r=0.67 ) . Continuous and interval exercise training result ed in a similar increase in OUES among patients with coronary artery disease . These findings suggest that improvements in OUES among CAD patients after aerobic exercise training may be dependent on peripheral and central mechanisms BACKGROUND Peak oxygen uptake ( Vo(2peak ) ) strongly predicts mortality in cardiac patients . We compared the effects of aerobic interval training ( AIT ) versus moderate continuous training ( MCT ) on Vo(2peak ) and quality of life after coronary artery bypass grafting ( CABG ) . METHODS Fifty-nine CABG patients were r and omized to either AIT at 90 % of maximum heart rate or MCT at 70 % of maximum heart rate , 5 d/wk , for 4 weeks at a rehabilitation center . Primary outcome was Vo(2peak ) , at baseline , after rehabilitation ( 4 weeks ) , and after 6 months of home-based exercise ( 6 months ) . RESULTS Vo(2peak ) increased between baseline and 4 weeks in AIT ( 27.1 + /- 4.5 vs 30.4 + /- 5.5 mL.kg(-1).min(-1 ) , P < .001 ) and MCT ( 26.2 + /- 5.2 vs 28.5 + /- 5.6 mL.kg(-1).min(-1 ) , P < .001 ; group difference , not significant ) . Aerobic interval training increased Vo(2peak ) between 4 weeks and 6 months ( 30.4 + /- 5.5 vs 32.2 + /- 7.0 mL.kg(-1).min(-1 ) , P < .001 ) , with no significant change in MCT ( 28.5 + /- 5.6 vs 29.5 + /- 5.7 mL.kg(-1).min(-1 ) ) . Quality of life improved in both groups from baseline to 4 weeks , remaining improved at 6 months . There were no changes in echocardiographic systolic and diastolic left ventricular function . Adiponectin increased between 4 weeks and 6 months in both groups ( group differences , not significant ) . CONCLUSIONS Four weeks of intense training increased Vo(2peak ) significantly after both AIT and MCT . Six months later , the AIT group had a significantly higher Vo(2peak ) than MCT . The results indicate that AIT and MCT increase Vo(2peak ) similarly in the short term , but with better long-term effect of AIT after CABG We found that interval training provides an effective means to improve the cardiovascular fitness and health status of highly functional patients with coronary artery disease . We also revealed that interval training improves anaerobic tolerance to a greater extent than the traditional exercise training model without increasing the risk to the patient . This research supports the implementation of interval training for highly functional patients with coronary artery disease Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective Peak oxygen uptake ( VO2peak ) is a strong predictor of survival in cardiac patients . The aims of this study were to compare the effects of high interval training ( HIT ) to moderate continuous training ( MCT ) on VO2peak and to identify the safety of HIT in acute myocardial infa rct ion patients with drug-eluting stent . Design Twenty-eight acute myocardial infa rct ion patients with drug-eluting stent were r and omized to either HIT at 85%–95 % of heart rate reserve or MCT at 70%–85 % of heart rate reserve , 3 days a week for 6 wks at a cardiac rehabilitation clinic . Primary outcome was VO2peak at baseline and after cardiac rehabilitation . Results Both HIT and MCT groups showed significant increases in VO2peak and heart rate recovery after 6 wks of training . The 22.16 % improvement in VO2peak in the HIT group was significantly greater than the 8.48 % improvement in the MCT group ( P = 0.021 ) . There were no cardiovascular events related to both HIT and MCT . Conclusions HIT is more effective than MCT for improving VO2peak in acute myocardial infa rct ion patients with drug-eluting stent . These findings may have important implication s for more effective exercise training in cardiac rehabilitation program OBJECTIVE : The purpose of this study was to evaluate the following : 1 ) the effects of continuous exercise training and interval exercise training on the end-tidal carbon dioxide pressure ( PETCO2 ) response during a grade d exercise test in patients with coronary artery disease ; and 2 ) the effects of exercise training modalities on the association between PETCO2 at the ventilatory anaerobic threshold ( VAT ) and indicators of ventilatory efficiency and cardiorespiratory fitness in patients with coronary artery disease . METHODS : Thirty-seven patients ( 59.7±1.7 years ) with coronary artery disease were r and omly divided into two groups : continuous exercise training ( n = 20 ) and interval exercise training ( n = 17 ) . All patients performed a grade d exercise test with respiratory gas analysis before and after three months of the exercise training program to determine the VAT , respiratory compensation point ( RCP ) and peak oxygen consumption . RESULTS : After the interventions , both groups exhibited increased cardiorespiratory fitness . Indeed , the continuous exercise and interval exercise training groups demonstrated increases in both ventilatory efficiency and PETCO2 values at VAT , RCP , and peak of exercise . Significant associations were observed in both groups : 1 ) continuous exercise training ( PETCO2VAT and cardiorespiratory fitness r = 0.49 ; PETCO2VAT and ventilatory efficiency r = -0.80 ) and 2 ) interval exercise training ( PETCO2VAT and cardiorespiratory fitness r = 0.39 ; PETCO2VAT and ventilatory efficiency r = -0.45 ) . CONCLUSIONS : Both exercise training modalities showed similar increases in PETCO2 levels during a grade d exercise test in patients with coronary artery disease , which may be associated with an improvement in ventilatory efficiency and cardiorespiratory fitness Aims . High-intensity interval training ( HIIT ) leads to improvements in various markers of cardiometabolic health but adherence to HIIT following a supervised laboratory intervention has yet to be tested . We compared self-report and objective measures of physical activity after one month of independent exercise in individuals with prediabetes who were r and omized to HIIT ( n = 15 ) or traditional moderate-intensity continuous training ( MICT , n = 17 ) . Method . After completing 10 sessions of supervised training participants were asked to perform HIIT or MICT three times per week for four weeks . Results . Individuals in HIIT ( 89 ± 11 % ) adhered to their prescribed protocol to a greater extent than individuals in MICT ( 71 ± 31 % ) as determined by training logs completed over one-month follow-up ( P = 0.05 , Cohen 's d = 0.75 ) . Minutes spent in vigorous physical activity per week measured by accelerometer were higher in HIIT ( 24 ± 18 ) as compared to MICT ( 11 ± 10 ) at one-month follow-up ( P = 0.049 , Cohen 's d = 0.92 ) . Cardiorespiratory fitness and systolic blood pressure assessed at one-month follow-up were equally improved ( P 's < 0.05 ) . Conclusions . This study provides preliminary evidence that individuals with prediabetes can adhere to HIIT over the short-term and do so at a level that is greater than MICT Background . We tested the hypothesis that high intensity interval training ( HIIT ) would be more effective than moderate intensity continuous training ( MIT ) to improve newly emerged markers of cardiorespiratory fitness in coronary heart disease ( CHD ) patients , as the relationship between ventilation and carbon dioxide production ( VE/VCO2 slope ) , oxygen uptake efficiency slope ( OUES ) , and oxygen pulse ( O2P ) . Methods . Seventy-one patients with optimized treatment were r and omly assigned into HIIT ( n = 23 , age = 56 ± 12 years ) , MIT ( n = 24 , age = 62 ± 12 years ) , or nonexercise control group ( CG ) ( n = 24 , age = 64 ± 12 years ) . MIT performed 30 min of continuous aerobic exercise at 70–75 % of maximal heart rate ( HRmax ) , and HIIT performed 30 min sessions split in 2 min alternate bouts at 60%/90 % HRmax ( 3 times/week for 16 weeks ) . Results . No differences among groups ( before versus after ) were found for VE/VCO2 slope or OUES ( P > 0.05 ) . After training the O2P slope increased in HIIT ( 22 % , P < 0.05 ) but not in MIT ( 2 % , P > 0.05 ) , while decreased in CG ( −20 % , P < 0.05 ) becoming lower versus HIIT ( P = 0.03 ) . Conclusion . HIIT was more effective than MIT for improving O2P slope in CHD patients , while VE/VCO2 slope and OUES were similarly improved by aerobic training regimens versus controls Exercise adherence is affected by factors including perceptions of enjoyment , time availability , and intrinsic motivation . Approximately 50 % of individuals withdraw from an exercise program within the first 6 mo of initiation , citing lack of time as a main influence . Time efficient exercise such as high intensity interval training ( HIIT ) may provide an alternative to moderate intensity continuous exercise ( MICT ) to elicit substantial health benefits . This study examined differences in enjoyment , affect , and perceived exertion between MICT and HIIT . Twelve recreationally active men and women ( age = 29.5 ± 10.7 yr , VO2max = 41.4 ± 4.1 mL/kg/min , BMI = 23.1 ± 2.1 kg/m2 ) initially performed a VO2max test on a cycle ergometer to determine appropriate workloads for subsequent exercise bouts . Each subject returned for two additional exercise trials , performing either HIIT ( eight 1 min bouts of cycling at 85 % maximal workload ( Wmax ) with 1 min of active recovery between bouts ) or MICT ( 20 min of cycling at 45 % Wmax ) in r and omized order . During exercise , rating of perceived exertion ( RPE ) , affect , and blood lactate concentration ( BLa ) were measured . Additionally , the Physical Activity Enjoyment Scale ( PACES ) was completed after exercise . Results showed higher enjoyment ( p = 0.013 ) in response to HIIT ( 103.8 ± 9.4 ) versus MICT ( 84.2 ± 19.1 ) . Eleven of 12 participants ( 92 % ) preferred HIIT to MICT . However , affect was lower ( p<0.05 ) and HR , RPE , and BLa were higher ( p<0.05 ) in HIIT versus MICT . Although HIIT is more physically dem and ing than MICT , individuals report greater enjoyment due to its time efficiency and constantly changing stimulus . Trial Registration : NCT:02981667 Objective : Exercise capacity strongly predicts survival and aerobic interval training ( AIT ) increases peak oxygen uptake effectively in cardiac patients . Usual care in Norway provides exercise training at the hospitals following myocardial infa rct ion ( MI ) , but the effect and actual intensity of these rehabilitation programmes are unknown . Design : R and omized controlled trial . Setting : Hospital cardiac rehabilitation . Subjects : One hundred and seven patients , recruited two to 12 weeks after MI , were r and omized to usual care rehabilitation or treadmill AIT . Interventions : Usual care aerobic group exercise training or treadmill AIT as 4 × 4 minutes intervals at 85–95 % of peak heart rate . Twice weekly exercise training for 12 weeks . Main measures : The primary outcome measure was peak oxygen uptake . Second Output:	Conclusion HIIT is superior to MICT in improving cardiorespiratory fitness in participants of cardiac rehabilitation ( CR ) . Improvements in cardiorespiratory fitness are significant for CR programs of > 6-week duration . Programs of 7 - 12 weeks ' duration result ed in the largest improvements in cardiorespiratory fitness for patients with coronary artery disease . HIIT appears to be as safe as MICT for CR participants
MS21654	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Malignant glioma is a devastating brain tumor with no effective treatment . This r and omised , controlled study involved 36 patients with operable primary or recurrent malignant glioma . Seventeen patients were r and omized to receive AdvHSV-tk gene therapy ( 3 x 10(10 ) pfu ) by local injection into the wound bed after tumor resection , followed by intravenous ganciclovir ( GCV ) , 5 mg/kg twice daily for 14 days . The control group of 19 patients received st and ard care consisting of radical excision followed by radiotherapy in those patients with primary tumors . The primary end-point was survival as defined by death or surgery for recurrence . Secondary end-points were all-cause mortality and tumour progression as determined by MRI . Overall safety and quality of life were also assessed . Findings were also compared with historical controls ( n = 36 ) from the same unit over 2 years preceding the study . AdvHSV-tk treatment produced a clinical ly and statistically significant increase in mean survival from 39.0 + /- 19.7 ( SD ) to 70.6 + /- 52.9 weeks ( P = 0.0095 , log-rank regression vs. r and omized controls ) . The median survival time increased from 37.7 to 62.4 weeks . Six patients had increased anti-adenovirus antibody titers , without adverse effects . The treatment was well tolerated . It is concluded that AdvHSV-tk gene therapy with GCV is a potential new treatment for operable primary or recurrent high- grade glioma The management of patients with glioblastoma remains challenging with an average survival of 32–56 weeks . We report on a clinical trial of patients with recurrent glioblastoma treated with adenovirus/herpex simplex-thymidine kinase/ganciclovir (ADV/HSV-tk/GC).Entry criteria for this study included : recurrent malignant glioma after surgical resection and conventional radiation therapy . At the time of recurrence , computerized volumetric resection of the tumor was performed and the ADV/HSV-tk complex was injected in the tumor bed . GC was administered 24 h after surgery ( 10 mg/kg/day ) for 7 days . Patients were divided into 3 ADV/HSV-tk dose-escalating cohorts . Adenoviral vector shedding , and local or systemic toxicity did not occur in this study . Magnetic resonance imaging showed lack of increased brain edema in the treated patients . Histological examination of the 5 patients that had repeated surgery after gene therapy treatment showed lack of tissue toxicity . Additionally , PCR for HSV-tk was negative in the brain 3 months after injection . The patients ' Karnofsky score was maintained ≥70 in 8/10 patients ( 80 % ) and 5/9 patients ( 55 % ) 3 and 6 months respectively , after gene therapy . Ten of 11 patients survived ≥52 weeks from diagnosis with an average survival of 112.3 weeks . One patient is still alive 248 weeks from diagnosis . These data show that the ADV/HSV-tk/GC complex at the dose used in this study is safe . Additional dose escalation is currently in progress Between December 1996 and September 1998 , 13 patients with advanced recurrent malignant brain tumors ( 9 with glioblastoma multiforme , 1 with gliosarcoma , and 3 with anaplastic astrocytoma ) were treated with a single intratumoral injection of 2 x 10(9 ) , 2 x 10(10 ) , 2 x 10(11 ) , or 2 x 10(12 ) vector particles ( VP ) of a replication-defective adenoviral vector bearing the herpes simplex virus thymidine kinase gene driven by the Rous sarcoma virus promoter ( Adv . RSVtk ) , followed by ganciclovir ( GCV ) treatment . The VP to infectious unit ratio was 20:1 . Our primary objective was to determine the safety of this treatment . Injection of Adv . RSVtk in doses < = = 2 x 10(11 ) VP , followed by GCV , was safely tolerated . Patients treated with the highest dose , 2 x 10(12 ) VP , exhibited central nervous system toxicity with confusion , hyponatremia , and seizures . One patient is living and stable 29.2 months after treatment . Two patients survived > 25 months before succumbing to tumor progression . Ten patients died within 10 months of treatment , 9 from tumor progression and 1 with sepsis and endocarditis . Neuropathologic examination of postmortem tissue demonstrated cavitation at the injection site , intratumoral foci of coagulative necrosis , and variable infiltration of the residual tumor with macrophages and lymphocytes To determine the safety and evaluate the efficacy of repeated administration of virus-producing cells ( GLI 328 ) containing the herpes simplex virus thymidine-kinase gene followed by ganciclovir treatment in adults with recurrent glioblastoma multiforme , we conducted a phase I/II multi-institutional trial . Eligible patients underwent surgical resection of tumor , followed by injections of vector producing cells ( VPC ) into the brain adjacent to the cavity . An Ommaya reservoir placed after surgery was used to inject a further dose of VPC seven days after surgery , followed seven days later by ganciclovir . Further gene therapy was given at 28-day intervals for up to a total of five cycles . Toxicity and anti-tumor effect were assessed . Of 30 patients who enrolled in the study , 16 experienced serious adverse events possibly related to the experimental therapy . Laboratory testing , including polymerase chain reaction analysis to detect replication-competent retrovirus in peripheral blood lymphocytes and tissues , as well as co-cultivation bioassays , were negative . Before receiving ganciclovir , 37 % of the patients showed evidence of transduced peripheral blood leukocytes , but only 12 % showed a persistence of transduced cells at the end of the first cycle of ganciclovir . Median survival was 8.4 months . Twenty percent of the patients ( n = 6 ) survived more than 12 months from the date of study entry . This treatment modality is feasible and appears to have some evidence of efficacy . Toxicity may be related in part to the method of gene delivery PURPOSE Despite aggressive therapies , median survival for malignant gliomas is less than 15 months . Patients with unmethylated O(6)-methylguanine-DNA methyltransferase ( MGMT ) fare worse , presumably because of temozolomide resistance . AdV-tk , an adenoviral vector containing the herpes simplex virus thymidine kinase gene , plus prodrug synergizes with surgery and chemoradiotherapy , kills tumor cells , has not shown MGMT dependency , and elicits an antitumor vaccine effect . PATIENTS AND METHODS Patients with newly diagnosed malignant glioma received AdV-tk at 3 × 10(10 ) , 1 × 10(11 ) , or 3 × 10(11 ) vector particles ( vp ) via tumor bed injection at time of surgery followed by 14 days of valacyclovir . Radiation was initiated within 9 days after AdV-tk injection to overlap with AdV-tk activity . Temozolomide was administered after completing valacyclovir treatment . RESULTS Accrual began December 2005 and was completed in 13 months . Thirteen patients were enrolled and 12 completed therapy , three at dose levels 1 and 2 and six at dose level 3 . There were no dose-limiting or significant added toxicities . One patient withdrew before completing prodrug because of an unrelated surgical complication . Survival at 2 years was 33 % and at 3 years was 25 % . Patient-reported quality of life assessed with the Functional Assessment of Cancer Therapy-Brain ( FACT-Br ) was stable or improved after treatment . A significant CD3(+ ) T-cell infiltrate was found in four of four tumors analyzed after treatment . Three patients with MGMT unmethylated glioblastoma multiforme survived 6.5 , 8.7 , and 46.4 months . CONCLUSION AdV-tk plus valacyclovir can be safely delivered with surgery and accelerated radiation in newly diagnosed malignant gliomas . Temozolomide did not prevent immune responses . Although not powered for efficacy , the survival and MGMT independence trends are encouraging . A phase II trial is ongoing Abstract Object : In mouse models of prostate and breast cancer therapeutic effects are enhanced when adenoviral HSV TK gene therapy is combined with ionizing radiation . In the present study , we adopted this approach for the treatment of human glioblastoma xenografts in an athymic mouse model and assessed treatment results as well as toxic side effects . Methods : About 72 nude mice received intracerebral inoculations of 2 × 105 U87ΔEGFR cells . On day 7 after tumor implantation the study population was r and omized into six treatment arms : ( 1 ) intratumoral buffer inoculation on day 7 , ( 2 ) intratumoral adenoviral vector injection ( 2 × 109 vp ) on day 7 , ( 3 ) single dose radiation ( 2.1 Gy ) on day 9 , ( 4 ) adenoviral injection + radiation , ( 5 ) adenoviral injection + ganciclovir ( GCV ) ( 20 ug/g twice daily from day 8 to 17 ) , ( 6 ) adenoviral injection + GCV + radiation . On day 21 half of the animals were sacrificed for histological evaluation of the brain tumors , the other half was assessed for survival . Results : This study showed significantly prolonged median survival time of 5 days for the GCV treated groups . The addition of radiation decreased the frequency of neurological symptoms and delayed the onset of deficits without altering the expression of thymidine kinase in the tumor cells . Conclusions : We conclude that adenoviral HSV TK gene therapy in combination with adjuvant radiotherapy does not generate increased toxic side effects in glioblastoma treatment . The prolonged survival time of animals receiving gene therapy and the reduced occurrence of neurological symptoms in irradiated mice constitute promising features of the combined treatment Herpes simplex virus thymidine kinase ( HSV tk ) gene therapy combined with ganciclovir ( GCV ) medication is a potential new method for the treatment of malignant glioma . We have used both retrovirus-packaging cells ( PA317/tk ) and adenoviruses ( Adv/tk ) for gene therapy for malignant glioma . Retrovirus-packaging cells were used for eight tumors in seven patients and adenoviruses were used for seven tumors in seven patients . As a control group , seven tumors in seven patients were transduced with lacZ marker gene 4 - 5 days before tumor resection . Safety and efficacy of the gene therapy were studied with clinical evaluation , blood and urine sample s , MRI follow-up , and survival of the patients . Four patients with adenovirus injections had a significant increase in anti-adenovirus antibodies and two of them had a short-term fever reaction . Frequency of epileptic seizures increased in two patients . No other adverse events possibly related to gene therapy were detected . In the retrovirus group , all treated gliomas showed progression by MRI at the 3-month time point , whereas three of the seven patients treated with Adv/tk remained stable ( p < 0.05 ) . Mean survival times for retrovirus , adenovirus , and control groups were 7.4 , 15.0 , and 8 . 3 months , respectively . The difference in the survival times between the adenovirus and retrovirus groups was significant ( p < 0.012 ) . It is concluded that HSV tk gene therapy is safe and well tolerated . On the basis of these results further trials are justified , especially with adenovirus vectors Intratumoral implantation of murine cells modified to produce retroviral vectors containing the herpes simplex virus-thymidine kinase ( HSV-TK ) gene induces regression of experimental brain tumors in rodents after ganciclovir ( GCV ) administration . We evaluated this approach in 15 patients with progressive growth of recurrent malignant brain tumors . Antitumor activity was detected in five of the smaller tumors ( 1.4 ± 0.5 ml ) . In situ hybridization for HSV-TK demonstrated survival of vector-producing cells ( VPCs ) at 7 days but indicated limited gene transfer to tumors , suggesting that indirect , “ byst and er , ” mechanisms provide local antitumor activity in human tumors . However , the response of only very small tumors in which a high density of vector-producing cells had been placed suggests that techniques to improve delivery and distribution of the therapeutic gene will need to be developed if clinical utility is to be achieved with this approach Previous uncontrolled clinical trials have shown the in vivo retrovirus (RV)-mediated transduction of glioblastoma cells with the herpes simplex virus thymidine kinase ( HSV-tk ) gene and subsequent systemic treatment with ganciclovir to be feasible and well tolerated . However , because of continued tumor progression in most patients , the antitumor effect could not be determined using historical controls . Here , we describe a phase III , multicenter , r and omized , open-label , parallel-group , controlled trial of the technique in the treatment of 248 patients with newly diagnosed , previously untreated glioblastoma multiforme ( GBM ) . Patients received , in equal numbers , either st and ard therapy ( surgical resection and radiotherapy ) or st and ard therapy plus adjuvant gene therapy during surgery . Progression-free median survival in the gene therapy group was Output:	Based on the best available evidence , it appears that adding gene therapy with HSV-tk has some effect in treating HGG patients , especially with respect to MST . However , neither the pooled analysis of OS , nor the combined analysis of tumor progress indicates any significant advantage to adding gene therapy compared with st and ard treatment alone .
MS21655	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : Proinflammatory cytokines , especially tumour necrosis factor α ( TNF-α ) , play a prominent role in the pathogenesis of cancer cachexia . Thalidomide , which is an inhibitor of TNF-α synthesis , may represent a novel and rational approach to the treatment of cancer cachexia . Aims : To assess the safety and efficacy of thalidomide in attenuating weight loss in patients with cachexia secondary to advanced pancreatic cancer . Methods : Fifty patients with advanced pancreatic cancer who had lost at least 10 % of their body weight were r and omised to receive thalidomide 200 mg daily or placebo for 24 weeks in a single centre , double blind , r and omised controlled trial . The primary outcome was change in weight and nutritional status . Results : Thirty three patients ( 16 control , 17 thalidomide ) were evaluated at four weeks , and 20 patients ( eight control , 12 thalidomide ) at eight weeks . At four weeks , patients who received thalidomide had gained on average 0.37 kg in weight and 1.0 cm3 in arm muscle mass ( AMA ) compared with a loss of 2.21 kg ( absolute difference −2.59 kg ( 95 % confidence interval ( CI ) −4.3 to −0.8 ) ; p = 0.005 ) and 4.46 cm3 ( absolute difference −5.6 cm3 ( 95 % CI −8.9 to −2.2 ) ; p = 0.002 ) in the placebo group . At eight weeks , patients in the thalidomide group had lost 0.06 kg in weight and 0.5 cm3 in AMA compared with a loss of 3.62 kg ( absolute difference −3.57 kg ( 95 % CI −6.8 to −0.3 ) ; p = 0.034 ) and 8.4 cm3 ( absolute difference −7.9 cm3 ( 95 % CI −14.0 to −1.8 ) ; p = 0.014 ) in the placebo group . Improvement in physical functioning correlated positively with weight gain ( r = 0.56 , p = 0.001 ) . Conclusion : Thalidomide was well tolerated and effective at attenuating loss of weight and lean body mass in patients with cachexia due to advanced pancreatic cancer Background : The approval of a research ethics committee ( REC ) and obtaining informed consent from patients ( ICP ) could be considered the main issues in the ethics of research with human beings . The aim of this study was to assess both method ological quality and ethical quality , and also to assess the relationship between these two qualities in r and omised phase III cancer trials . Method : Method ological quality ( Jadad score ) and ethical quality ( Berdeu score ) were assessed for all r and omised controlled trials ( RCTs ) published in 10 international journals between 1999 and 2001 ( n = 231 ) . Results : The mean Jadad score was 9.86 ± 1.117 . The method ological quality was poor in 75 RCTs ( Jadad score < 9 ) . The mean Berdeu score was 0.42 ± 0.133 . The mean ethical quality score for poor method ological quality RCTs ( n = 75 ) was 0.39 ± 0.133 ; it was 0.43 ± 0.133 for good ( n = 156 ) method ological quality RCTs ( p = 0.07 ) . There was improvement in ethical quality according to the year of commencement of the trials ( p < 0.001 ) . There was no correlation between method ological quality and the number of participating patients ( R2 = 0.003 , p = 0.78 ) , between ethical quality and the number of participating patients ( R2 = 0.003 , p = 0.76 ) , or between ethical quality and method ological quality ( R2 = 0.012 , p = 0.1 ) . ICP and REC approval were not obtained for 21 and 77 trials respectively . Conclusion : The association between method ological quality and the reporting of ethical requirements probably reflects the respect shown for patients during the whole research process . These results suggest that closer attention to the conduct of clinical research , as well as the reporting of its ethical aspects , is needed The primary purpose of this study was to investigate the accuracy of the activPAL physical activity monitor in measuring step number and cadence in older adults . Two pedometers ( New-Lifestyles Digi-Walker SW-200 and New-Lifestyles NL2000 ) used in clinical practice to count steps were simultaneously evaluated . Observation was the criterion measure . Twenty-one participants ( 65 - 87 yr old ) recruited from community-based exercise classes walked on a treadmill at 5 speeds ( 0.67 , 0.90 , 1.12 , 1.33 , and 1.56 m/s ) and outdoors at 3 self-selected speeds ( slow , normal , and fast ) . The absolute percentage error of the activPAL was < 1 % for all treadmill and outdoor conditions for measuring steps and cadence . With the exception of the slowest treadmill speed , the NL-2000 error was < 2 % . The SW-200 was the least accurate device , particularly at slower walking speeds . The activPAL monitor accurately recorded step number and cadence . Combined with its ability to identify primary postures , the activPAL might be a useful and versatile device for measuring activity in older adults Summary The use of megestrol acetate in the treatment of weight loss in gastrointestinal cancer patients has been disappointing . The aim of the present study was to compare the combination of megestrol acetate and placebo with megestrol acetate and ibuprofen in the treatment of weight loss in such patients . At baseline , 4–6 weeks and 12 weeks , patients underwent measurements of anthropometry , concentrations of albumin and C-reactive protein and assessment of appetite , performance status and quality of life using EuroQol-EQ-5D and EORTC QLQ-C30 . Thirty-eight and 35 patients ( median weight loss 18 % ) were r and omized to megestrol acetate/placebo or megestrol acetate/ibuprofen , respectively , for 12 weeks . Forty-six ( 63 % ) of patients failed to complete the 12-week assessment . Of those evaluable at 12 weeks , there was a decrease in weight ( median 2.8 kg ) in the megestrol acetate/placebo group compared with an increase ( median 2.3 kg ) in the megestrol acetate/ibuprofen group ( P < 0.001 ) . There was also an improvement in the EuroQol-EQ-5D quality of life scores of the latter group ( P < 0.05 ) . The combination of megestrol acetate/ibuprofen appeared to reverse weight loss and appeared to improve quality of life in patients with advanced gastrointestinal cancer . Further trials of this novel regimen in weight-losing patients with hormone-insensitive cancers are warranted The aim of this study was to investigate the effect of the cyclo-oxygenase inhibitor ibuprofen on the acute-phase protein response and resting energy expenditure ( REE ) of weight-losing patients with pancreatic cancer . Patients with irresectable pancreatic cancer ( n = 16 ) were treated with either ibuprofen ( 1200 mg day-1 for 7 days ( n = 10 ) or placebo ( n = 6 ) . A group of 17 age-related non-cancer subjects were also studied . Indirect calorimetry , anthropometry , multifrequency bioelectrical impedence analysis and serum C-reactive protein ( CRP ) estimation were performed immediately before and after treatment . Before treatment , total REE was significantly elevated in the pancreatic cancer patients compared with healthy controls ( 1499 + /- 71 vs 1377 + /- 58 kcal ) ( P < 0.02 ) . Following treatment the mean REE of the ibuprofen group fell significantly ( 1386 + /- 89 kcal ) compared with pretreatment values ( 1468 + /- 99 kcal ) ( P < 0.02 ) , whereas no change was observed in the placebo group . Serum CRP concentration was also reduced in the ibuprofen-treated group ( pre-ibuprofen , 51 mg l-1 ; post-ibuprofen , 29 mg l-1 ; P < 0.05 ) . These results suggest that ibuprofen may have a role in abrogating the catabolic processes which contribute to weight loss in patients with pancreatic cancer The regulation of acute phase protein production and the relationship of the acute phase protein response to tumour growth was examined in colorectal cancer patients ( n = 9 ) . Ibuprofen ( 1200 mg/d ) was administered for 8 - 11 days . Following ibuprofen administration there were reductions in circulating concentrations of C-reactive protein ( P = 0.01 ) , interleukin-6 ( P = 0.06 ) , cortisol ( P = 0.04 ) and also in the platelet count ( P = 0.01 ) . There was no significant change in albumin , insulin and carcinoembryonic antigen . These results indicate that ibuprofen administered over a prolonged period substantially reduces acute protein production via its effect on interleukin-6 and cortisol . It remains to be determined whether ibuprofen is useful in moderating tumour growth in colorectal cancer patients PURPOSE A phase III , r and omized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia-lean body mass ( LBM ) , resting energy expenditure ( REE ) , and fatigue- and relevant secondary endpoints : appetite , quality of life , grip strength , Glasgow Prognostic Score ( GPS ) and proinflammatory cytokines . PATIENTS AND METHODS Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were r and omly assigned to one of five treatment arms : arm 1 , medroxyprogesterone ( 500 mg/day ) or megestrol acetate ( 320 mg/day ) ; arm 2 , oral supplementation with eicosapentaenoic acid ; arm 3 , L-carnitine ( 4 g/day ) ; arm 4 , thalidomide ( 200 mg/day ) ; and arm 5 , a combination of the above . Treatment duration was 4 months . RESULTS Analysis of variance showed a significant difference between treatment arms . A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints . An analysis of changes from baseline showed that LBM ( by dual-energy X-ray absorptiometry and by L3 computed tomography ) significantly increased in arm 5 . REE decreased significantly and fatigue improved significantly in arm 5 . Appetite increased significantly in arm 5 ; interleukin (IL)-6 decreased significantly in arm 5 and arm 4 ; GPS and Eastern Cooperative Oncology Group performance status ( ECOG PS ) score decreased significantly in arm 5 , arm 4 , and arm 3 . Toxicity was quite negligible , and was comparable between arms . CONCLUSION The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite , IL-6 , GPS , and ECOG PS score was the combination regimen that included all selected agents Abstract Under the common denomination of Systemic Immune-Metabolic Syndrome ( SIMS ) , we grouped many symptoms that share a similar pathophysiologic background . SIMS is the result of the dysfunctional interaction of tumor cells , stroma cells , and the immune system , leading to the release of cytokines and other systemic mediators such as eicosanoids . SIMS includes systemic syndromes such as paraneoplastic hemopathies , hypercalcemia , coagulopathies , fatigue , weakness , cachexia , chronic nausea , anorexia , and early satiety among others . Eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil can help in the management of persistent chronic inflammatory states , but treatment 's compliance is generally poor . Preferentially , Cox-2 inhibition can create a favorable pattern of cytokines by decreasing the production of certain eicosanoids , although their role in SIMS is unknown . The aim of this study was to test the hypothesis that by modulating systemic inflammation through an eicosanoid-targeted approach , some of the symptoms of the SIMS could be controlled . We exclusively evaluated 12 patients for compliance . Patients were assigned 1 of the 4 treatment groups ( 15- , 12- , 9- , or 6-g dose , fractionated every 8 h ) . For patients assigned to 15 and 12 doses , the overall compliance was very poor and unsatisfactory for patients receiving the 9-g dose . The maximum tolerable dose was calculated to be around 2 capsules tid ( 6 g of fish oil per day ) . A second cohort of 22 patients with advanced lung cancer and SIMS were r and omly assigned to receive either fish oil , 2 g tid , plus placebo capsules bid ( n = 12 ) or fish oil , 2 g tid , plus celecoxib 200 mg bid ( n = 10 ) . All patients in both groups received oral food supplementation . After 6 wk of treatment , patients receiving fish oil + placebo or fish oil + celecoxib showed significantly more appetite , less fatigue , and lower C-reactive protein ( C-RP ) values than their respective baselines values ( P < 0.02 for all the comparisons ) . Additionally , patients in the fish oil + celecoxib group also improved their body weight and muscle strength compared to bas Output:	These studies provided some evidence of positive therapeutic effect on quality of life , performance status , inflammatory markers , weight gain and survival , but there was insufficient evidence demonstrated for their widespread use in practice .
MS21656	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objectives To evaluate the outcomes of preoperative transarterial chemoembolization ( TACE ) for resectable hepatocellular carcinoma ( HCC ) with portal vein invasion . Methods From February 2006 to July 2011 , 320 patients initially diagnosed with resectable HCC and portal vein invasion were prospect ively non-r and omized into two arms . In the immediate resection arm ( Arm 1 , n = 205 ) patients received immediate surgical resection . 115 patients were included in the preoperative TACE arm ( Arm 2 ) , and eventually 85 patients underwent TACE followed by surgical resection . Results The 1- , 3- and 5-year overall survival rates were 48.3 % , 18.7 % and 13.9 % for Arm 1 and 61.2 % , 31.7 % and 25.3 % for Arm 2 ( P = 0.001 ) , respectively . In the subgroup analysis of types I and II portal vein tumour thrombus ( PVTT ) , the preoperative TACE arm demonstrated significantly better survival rates than the immediate resection arm ( PI = 0.001 , PII = 0.036 ) . However , no significant difference was found for patients with type III PVTT ( PIII = 0.684 ) . No significant difference was found between the two arms in terms of complications and mortality . Conclusions Preoperative TACE seems to confer a survival benefit for resectable HCC with PVTT , especially for types I and II PVTT , and preoperative TACE should therefore be recommended as a routine procedure . Key Points• Preoperative TACE improves the clinical outcomes for patients with PVTT• Preoperative TACE could significantly improve the rate of en bloc thrombectomy• Preoperative TACE does not increase the related adverse Background Different approaches to surgical treatment of portal vein tumor thrombosis ( PVTT ) have been advocated . This study investigated the outcomes of different surgical approaches in hepatocellular carcinoma ( HCC ) patients with PVTT . Methods We review ed prospect ively collected data for all patients who underwent hepatectomy for HCC at our hospital between December 1989 and December 2010 . Patients were excluded from analysis if they had extrahepatic disease , PVTT reaching the level of the superior mesenteric vein , or hepatectomy with a positive resection margin . The remaining patients were divided into three groups for comparison : group 1 , with ipsilateral PVTT resected in a hepatectomy ; group 2 , with PVTT extending to or beyond the portal vein bifurcation , treated by en bloc resection followed by portal vein reconstruction ; group 3 , with PVTT extending to or beyond the portal vein bifurcation , treated by thrombectomy . Results A total of 88 patients , with a median age of 54 years , were included in the analysis . Group 2 patients were younger , with a median age of 43.5 years versus 57 in group 1 and 49 in group 3 ( p = 0.017 ) . Group 1 patients had higher preoperative serum alpha-fetoprotein levels , with a median of 8,493 ng/mL versus 63.25 in group 2 and 355 in group 3 ( p = 0.004 ) , and shorter operation time , with a median of 467.5 min versus 663.5 in group 2 and 753 in group 3 ( p = 0.018 ) . No patient had thrombus in the main portal vein . Two ( 2.8 % ) hospital deaths occurred in group 1 and one ( 10 % ) in group 2 , but none in group 3 ( p = 0.440 ) . The rates of complication in groups 1 , 2 , and 3 were 31.9 , 50.0 , and 71.4 % , respectively ( p = 0.079 ) . The median overall survival duration s were 10.91 , 9.4 , and 8.58 months , respectively ( p = 0.962 ) , and the median disease-free survival duration s were 4.21 , 3.78 , and 1.51 months , respectively ( p = 0.363 ) . The groups also had similar patterns of disease recurrence ( intrahepatic : 33.8 vs. 28.6 vs. 40.0 % ; extrahepatic : 16.9 vs. 14.3 vs. 0 % ; both : 28.2 vs. 42.9 vs. 40.0 % ; no recurrence : 21.1 vs. 14.3 vs. 20.0 % ; p = 0.836 ) . Conclusions The three approaches have similar outcomes in terms of survival , complication , and recurrence . Effective adjuvant treatments need to be developed to counteract the high incidence of recurrence AIM To evaluate the efficacy of different treatment strategies for hepatocellular carcinoma ( HCC ) with portal vein tumor thrombosis ( PVTT ) and investigate factors influencing prognosis . METHODS One hundred and seventy-nine HCC patients with macroscopic PVTT were enrolled in this study . They were divided into four groups and underwent different treatments : conservative treatment group ( n = 18 ) , chemotherapy group ( n = 53 ) , surgical resection group ( n = 24 ) and surgical resection with postoperative chemotherapy group ( n = 84 ) . Survival rates of the patients were analyzed by the Kaplan-Meier method . A log-rank analysis was performed to identify group differences . Cox 's proportional hazards model was used to analyze variables associated with survival . RESULTS The mean survival periods of the patients in four groups were 3.6 , 7.3 , 10.1 , and 15.1 mo respectively . There were significant differences in the survival rates among the groups . The survival rates at 0.5- , 1- , 2- , and 3-year in surgical resection with postoperative chemotherapy group were 55.8 % , 39.3 % , 30.4 % , and 15.6 % respectively , which were significantly higher than those of other groups ( P<0.001 ) . Multivariate analysis revealed that the strategy of treatment ( P<0.001 ) and the number of chemotherapy cycles ( P = 0.012 ) were independent survival predictors for patients with HCC and PVTT . CONCLUSION Surgical resection of HCC and PVTT combined with postoperative chemotherapy or chemoembolization is the most effective therapeutic strategy for the patients who can tolerate operation . Multiple chemotherapeutic courses should be given postoperatively to the patients with good hepatic function reserve AIM To compare the therapeutic effect and significance s of multimodality treatment for hepatocellular carcinoma ( HCC ) with tumor thrombi in portal vein ( PVTT ) . METHODS HCC patients ( n=147 ) with tumor thrombi in the main portal vein or the first branch of portal vein were divided into four groups by the several therapeutic methods . There were conservative treatment group in 18 out of patients ( group A ) ; and hepatic artery ligation(HAL ) and /or hepatic artery infusion ( HAI ) group in 18 patients ( group B ) , in whom postoperative chemoembolization was done periodically ; group of removal of HCC with PVTT in 79 ( group C ) and group of transcatheter hepatic arterial chemoembolization ( TACE ) or HAI and /or portal vein infusion ( PVI ) after operation in 32 ( group D ) . RESULTS The median survival period was 12 months in our series and the 1-,3- , and 5-year survival rates were 44.3 % , 24.5 % and 15.2 % , respectively . The median survival times were 2 , 5 , 12 and 16 months in group A , B , C and D , respectively . The 1- , 3- and 5-year survival rates were 5.6 % , 0 % and 0 % in group A ; 22.2 % , 5.6 % and 0 % in group B ; 53.9 % , 26.9 % and 16.6 % in group C ; 79.3 % , 38.9 % and 26.8 % in group D , respectively . Significant difference appeared in the survival rates among the groups ( P < 0.05 ) . CONCLUSION Hepatic resection with removal of tumor thrombi and HCC should increase the curative effects and be encouraged for the prolongation of life span and quality of life for HCC patients with PVTT , whereas the best therapeutic method for HCC with PVTT is with regional hepatic chemotherapy or chemoembolization after hepatic resection with removal of tumor thrombi This study analyzed the natural history and prognostic factors of patients with nonsurgical hepatocellular carcinoma ( HCC ) . Twenty variables from 102 cirrhotic patients with HCC who were not treated within prospect i ve r and omized controlled trials ( RCT ) were investigated through uni‐ and multivariate analyses . None of them was suitable for radical therapies ( surgical resection , liver transplantation , or ethanol injection ) or presented end‐stage disease as reflected by an Okuda stage 3 or a Performance Status ≥3 . Sixty‐five patients were Child‐Pugh A , 34 were B , and 3 were C. Most of them exhibited a preserved Performance Status Test ( PST ) ( 0 = 56 ; 1 = 38 ; 2 = 8) . Tumor was solitary in 26 ( ≤5 cm in 16 ) and multinodular/massive in 76 . After a median follow‐up of 17 months , 79 patients died , the 1‐ , 2‐ , and 3‐year survival being 54 % , 40 % , and 28 % . The multivariate study identified PST ( P = .01 ) , constitutional syndrome ( P = .04 ) , vascular invasion ( P = .001 ) , and extrahepatic spread ( P = .04 ) as independent predictors for mortality . The 1‐ , 2‐ , and 3‐year survival for the 48 patients without adverse factors ( Stage 0 ) was 80 % , 65 % , and 50 % , respectively , and 29 % , 16 % , and 8 % in the 54 patients with at least one adverse parameter ( Stage I ) . Therefore , Stage 0 would correspond to an intermediate stage , while Stage I would represent an advanced status , before reaching an end‐stage phase . In conclusion , the outcome of nonsurgical HCC is not homogeneously grim and may be predicted by assessing the presence of symptoms and of an invasive tumoral pattern . Therapeutic trials should be design ed and evaluated considering these characteristics BACKGROUND & AIMS The Sorafenib Hepatocellular Carcinoma ( HCC ) Assessment R and omized Protocol ( SHARP ) trial demonstrated that sorafenib improves overall survival and is safe for patients with advanced HCC . In this trial , 602 patients with well-preserved liver function ( > 95 % Child-Pugh A ) were r and omized to receive either sorafenib 400 mg or matching placebo orally b.i.d . on a continuous basis . Because HCC is a heterogeneous disease , baseline patient characteristics may affect individual responses to treatment . In a comprehensive series of exploratory subgroup analyses , data from the SHARP trial were analyzed to discern if baseline patient characteristics influenced the efficacy and safety of sorafenib . METHODS Five subgroup domains were assessed : disease etiology , tumor burden , performance status , tumor stage , and prior therapy . Overall survival ( OS ) , time to progression ( TTP ) , disease control rate ( DCR ) , and safety were assessed for subgroups within each domain . RESULTS Subgroup analyses showed that sorafenib consistently improved median OS compared with placebo , as reflected by hazard ratios ( HRs ) of 0.50 - 0.85 , similar to the complete cohort ( HR=0.69 ) . Sorafenib also consistently improved median TTP ( HR , 0.40 - 0.64 ) , except in HBV-positive patients ( HR , 1.03 ) , and DCR . Results are limited by small patient numbers in some subsets . The most common grade 3/4 adverse events included diarrhea , h and -foot skin reaction , and fatigue ; the incidence of which did not differ appreciably among subgroups . CONCLUSIONS These exploratory subgroup analyses showed that sorafenib consistently improved median OS and DCR compared with placebo in patients with advanced HCC , irrespective of disease etiology , baseline tumor burden , performance status , tumor stage , and prior therapy Output:	Conclusions HR may lead to longer OS for some selected HCC patients with PVTT than TACE , especially for type I or II PVTT , with less difference being observed for type III or IV PVTT
MS21657	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : We evaluated the relationship of Chlamydia pneumoniae infection with prospect i ve lung cancer risk using traditional serologic markers [ microimmunoflourescence ( MIF ) IgG and IgA antibodies ] and Chlamydia heat shock protein-60 ( CHSP-60 ) antibodies , a marker for chronic chlamydial infection . Methods : We conducted a nested case-control study ( 593 lung cancers and 671 controls ) within the screening arm of the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial ( N = 77,464 ) . Controls were matched to cases by age , sex , r and omization year , follow-up time , and smoking ( pack-years of smoking , time since quitting ) . We assessed C. pneumoniae seropositivity and endpoint antibody titers ( IgG and IgA against C. pneumoniae elementary bodies and IgG against CHSP-60 ) . Results : C. pneumoniae seropositivity by microimmunoflourescence IgG or IgA antibodies was not associated with lung cancer [ odds ratio of 0.88 and 95 % confidence interval ( 95 % CI ) of 0.69 - 1.13 for IgG ; odds ratio of 0.98 and 95 % CI of 0.75 - 1.27 for IgA ] . In contrast , individuals seropositive for CHSP-60 IgG antibodies had significantly increased lung cancer risk ( odds ratio , 1.30 ; 95 % CI , 1.02 - 1.67 ) , and risk increased with increasing antibody titers ( P trend = 0.006 ) . CHSP-60–related risk did not differ significantly by lung cancer histology , follow-up time , or smoking . CHSP-60 seropositivity was associated with increased risk 2 to 5 years before lung cancer diagnosis ( odds ratio , 1.77 ; 95 % CI , 1.16 - 2.71 ; P trend = 0.006 ) , thus arguing against reverse causality . Conclusions : CHSP-60 seropositivity and elevated antibody titers were associated with significantly increased risk for subsequent lung cancer , supporting an etiologic role for C. pneumoniae infection in lung carcinogenesis . Impact : Our results highlight the potential for lung cancer risk reduction through treatments targeted toward C. pneumoniae infections and chronic pulmonary inflammation . Cancer Epidemiol Biomarkers Prev ; 19(6 ) ; 1498–505 . © 2010 AACR Chinese women in Hong Kong have among the highest incidence and mortality of lung cancer in the world , in spite of a low prevalence of smoking . We carried out this population -based case – control study to evaluate the associations of previous lung disease and family cancer history with the occurrence of lung cancer among them . We selected 212 cases that were newly diagnosed with primary lung cancer , and r and omly sample d 292 controls from the community , frequency matched by age group . All the cases and controls were lifetime nonsmokers . We estimated the main effects of preexisting asthma , pulmonary tuberculosis , pneumonia , chronic bronchitis , and family lung/all cancer history , using unconditional logistic regression , accounting for various potential risk factors and confounders . All of the previous lung diseases , except chronic bronchitis , were related to an elevated risk for lung cancer , and the association with asthma was significant . Those who had more than one previous lung disease tended to be at higher risk than those with only one of them . Positive family history of any cancer was associated with over 2-fold risk than negative family history . The joint effect of positive history of previous pulmonary diseases and positive family cancer history appeared to be additive , indicating the two factors acted independently . The results support an etiological link of preexisting lung disease and family cancer history to the risk of lung cancer RATIONALE Identification of risk factors for lung cancer can help in selecting patients who may benefit the most from smoking cessation interventions , early detection , or chemoprevention . OBJECTIVE To evaluate whether the presence of emphysema on low-radiation-dose CT ( LDCT ) of the chest is an independent risk factor for lung cancer . METHODS The study used data from a prospect i ve cohort of 1,166 former and current smokers participating in a lung cancer screening study . All individuals underwent a baseline LDCT and spirometry followed by yearly repeat LDCT studies . The incidence density of lung cancer among patients with and without emphysema on LDCT was estimated . Stratified and multiple regression analyses were used to assess whether emphysema is an independent risk factor for lung cancer after adjusting for age , gender , smoking history , and the presence of airway obstruction on spirometry . RESULTS On univariate analysis , the incidence density of lung cancer among individuals with and without emphysema on LDCT was 25.0 per 1,000 person-years and 7.5 per 1,000 person-years , respectively ( risk ratio [ RR ] , 3.33 ; 95 % confidence interval [ CI ] , 1.41 to 7.85 ) . Emphysema was also associated with increased risk of lung cancer when the analysis was limited to individuals without airway obstruction on spirometry ( RR , 4.33 ; 95 % CI , 1.04 to 18.16 ) . Multivariate analysis showed that the presence of emphysema ( RR , 2.51 ; 95 % CI , 1.01 to 6.23 ) on LDCT but not airway obstruction ( RR , 2.10 ; 95 % CI , 0.79 to 5.58 ) was associated with increased risk of lung cancer after adjusting for potential cofounders . CONCLUSIONS Results suggest that the presence of emphysema on LDCT is an independent risk factor for lung cancer BACKGROUND COPD is thought to be more prevalent among men than women , a finding usually attributed to higher smoking rates and more frequent occupational exposures of significance for men . However , smoking prevalence has increased among women and there is evidence that women may be more susceptible to the adverse pulmonary function effects of smoking than men . There may also be underdiagnosis and misdiagnosis of COPD in both sexes because objective measures of lung function are underused . OBJECTIVES We undertook the present study to determine if there is gender bias in the diagnosis of COPD , such that women are less likely than men to receive a diagnosis of COPD . We also attempted to determine if underuse of lung function measurements was a factor in any bias detected . METHODS We surveyed a r and om sample of 192 primary -care physicians ( 96 American and 96 Canadian ; 154 men and 38 women ) using a hypothetical case presentation and a structured interview . The case of cough and dyspnea in a smoker was presented in six versions differing only in the age and sex of the patient . After presentation of the history and physical findings , physicians were asked to state the most probable diagnosis and to choose the diagnostic studies needed . Physicians were then presented with spirometric findings of moderate or severe obstruction without significant bronchodilator response , and the questions repeated . Finally , the negative outcome of an oral steroid trial was described . RESULTS Initially , COPD was given as the most probable diagnosis significantly more often for men than women ( 58 % vs 42 % ; p < 0.05 ) . The likelihood of a COPD diagnosis increased significantly and initial differences between sexes decreased as objective information was provided . After spirometry , COPD diagnosis rates for men and women were 74 % vs 66 % ( p = not significant ) ; after the steroid trial 85 % vs 79 % ( p = not significant ) . Only 22 % of physicians would have requested spirometry after the initial presentation . CONCLUSIONS In North America , primary -care physicians underdiagnosed COPD , particularly in women . Spirometry reduces the risk of underdiagnosis and gender bias but is underused Abstract Objectives : While 75 - 90 % of people who develop lung cancer are smokers , only a small proportion of smokers develop lung cancer . Identifying factors that increase a smoker 's risk of developing lung cancer may help scientists to better underst and the etiology of lung cancer and more effectively target high-risk groups for screening . Methods : Information on physician-diagnosed non-malignant lung diseases [ asbestosis , asthma , chronic bronchitis or emphysema ( CB/E ) , pneumonia , and tuberculosis ] was obtained at baseline from 17,698 men and women involved in CARET , a r and omized lung cancer prevention trial of beta-carotene and vitamin A among heavy smokers and asbestos-exposed workers . Hazard ratios for lung cancer were estimated through Cox regression models , after controlling for potential confounding factors , included smoking . Analyses were restricted to former and current smokers . Results : During a median follow up of 9.1 years , 1028 cases of lung cancer occurred . Those who developed lung cancer were more likely to report a history of CB/E than controls ( adjusted HR = 1.29 , 95 % CI : 1.09 - 1.53 ) . In subgroup analyses , the association between a history of CB/E and lung cancer was stronger for those who were younger at diagnosis/reference , men in the heavy smoker cohort , former smokers , and those with squamous cell carcinomas . There was little association between a history of other lung diseases and lung cancer . Conclusions : Smokers with a history of CB/E may be at higher risk of developing lung cancer , independent of their smoking history Small cell carcinoma of the lung ( SCLC ) occurs most frequently in heavy smokers , yet exhibits a lesser predominance among men than other smoking-associated lung cancers . Incidence rates have increased more rapidly in women than men and at a faster rate among women than other cell types . To investigate the importance of smoking and other risk factors , a case-control study of SCLC in women was conducted . A total of 98 women with primary SCLC and 204 healthy controls , identified by r and om-digit dialing and frequency matched for age , completed telephone interviews . Data collected include demographics , medical history , family cancer history , residence history , and lifetime smoking habits . Odds ratios ( ORs ) and 95 % confidence intervals ( 95 % CI ) were calculated using logistic regression analysis . Risk for small cell carcinoma in women is strongly associated with current use of cigarettes . Ninety-seven of 98 cases had smoked cigarettes ; 79 % of cases were current smokers and 20 % were former smokers at the time of diagnosis compared to 13 % current and 34 % former smokers among controls . The ORs associated with smoking are 108.7 ( 95 % CI 14.8 - 801 ) for ever-use of cigarettes , 278.9 ( 95 % CI 37.0 - 2102 ) for current smoking , and 31.5 ( 95 % CI 4 . 1 - 241 ) for former smoking . Risk increases steeply with pack-years of smoking and decreases with duration of smoking cessation . After adjusting for age , education , and lifetime smoking history , medical history of physician-diagnosed respiratory disease including chronic bronchitis , emphysema , pneumonia , tuberculosis , asthma , and hay fever is not associated with a significant increase in lung cancer risk . Employment in blue collar , service , or other high risk occupations is associated with a two to three-fold non-significant increase in risk for small cell carcinoma after adjusting for smoking BACKGROUND China has 1.4 million new cases of tuberculosis every year , more than any country except India . A new tuberculosis control project based on short-course chemotherapy was introduced in half the country in 1991 , after a national survey of tuberculosis prevalence in 1990 . Another survey was done in 2000 to re-evaluate the national tuberculosis burden , providing the opportunity to assess the effect of the control project . METHODS The survey in 2000 identified 375599 eligible individuals at 257 investigation points chosen from all 31 mainl and provinces by stratified r and om sampling . Children ( aged 0 - 14 years ) were suspected of having tuberculosis if they had an in duration of 10 mm or greater after a tuberculin skin test , and an abnormal fluorograph . Adults were suspected if they had a persistent cough , abnormal fluorograph , or both . Tuberculosis was diagnosed by chest radiograph , sputum-smear microscopy , and culture . FINDINGS 365097 people were examined ( 97 % of those eligible ) . Prevalences of pulmonary , culture-positive , and smear-positive tuberculosis in 2000 were 367 ( 95 % CI 340 - 397 ) , 160 ( 144 - 177 ) , and 122 ( 110 - 137 ) per 100000 population , respectively . Between 1990 and 2000 , prevalences of these three forms of the disease had fallen , respectively , by 32 % ( 5 - 68 ) , 37 % ( 7 - 66 ) , and 32 % ( 9 - 51 ) more in areas in which the project was implemented than in non-project areas . For culture-positive disease , a 30 % ( 9 - 48 ) reduction was directly attributable to the project . INTERPRETATION Between 1991 and 2000 , prevalence of tuberculosis was reduced significantly in areas of China by use of short-course chemotherapy following WHO guidelines . We estimate that in 2000 , in a population of more than half a billion , there were 382000 fewer prevalent culture-positive Output:	Conclusions Previous lung diseases are associated with an increased risk of lung cancer with the evidence among never smokers supporting a direct relationship between previous lung diseases and lung cancer
MS21658	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The efficacy and safety of a low molecular weight heparin ( LMWH ) given as a single predialysis bolus injection was compared to st and ard heparin ( SH ) administered with a continuous infusion in a r and omized , 6 month , open follow-up study in 70 patients undergoing hemodialysis . No major bleeding or adverse events were encountered during a total of 4,000 dialysis procedures ( 2,000 with LMWH ) . Clot formation in the extracorporeal circuit was minimal and comparable between the groups at 4 , 13 , and 26 weeks after the start of the study . No accumulation of LMWH anticoagulant activity was noted . It is concluded that the use of LMWH is a safe , effective , and less complex alternative to SH Low molecular weight heparins ( LMWHs ) are used for prevention of clotting in the dialysis circuit . The aim of this trial was to define the optimal dose of a new LMWH and to test the efficiency of a single dose at the start of the session . Fifteen patients were treated according to a double blind and crossover design during 4 blocks of 5 consecutive reviparin doses assigned r and omly as 50 , 60 , 70 , 85 , and 100 IU anti-Xa/kg . Assessment was carried out on screening of fibrin rings or clots in the arterial and venous air traps and on visual detection of fiber in the dialyzer after rinsing . These clinical results were compared to plasmatic anti-Xa activity and thrombin-antithrombin ( TAT ) complex generation . A st and ard dose of 70 IU anti-Xa/kg of nadroparin was used as the control . After a bolus of 50 to 100 IU anti-Xa/kg , the occurrence of fibrin rings and clots in the air traps was dependent on three factors : dose of LMWH , time of the session , and patient status . A bolus of 85 IU anti-Xa/kg of reviparin was effective and safe for sessions of 4 h. For this dose , plasmatic anti-Xa activity was 0.96 + /- 0.28 IU/ml at Hour 2 and 0.82 + /- 0.22 IU/ml at Hour 4 . TAT complexes are good markers of the activation of the coagulation . They did not increase during a 4 h session after a reviparin bolus of 100 IU/kg . For the same LMWH dose , the trial shows a great variability of the clinical effect and anti-Xa activities from one patient to another . A single dose of 85 IU anti-Xa/kg of reviparin can be used at the start of the dialysis session as a loading dose . We advise adapting the dose during the subsequent sessions according to the appearance of the blood circuit . The benefit of monitoring anti-Xa activity and TAT complexes could be tested in a further trial We have performed a dose ranging study of a low MW heparin , Kabi 2165 , during haemodialysis in humans ( n = 16 ) and compared it to a dose of unfractionated commercial heparin that has already been shown to inhibit fibrin formation . Low MW heparin administered as 5000 or 10,000 anti-factor Xa units , s.c . , half an hour prior to the initiation of dialysis was unable to prevent fibrin formation in the dialyser circuit . A single bolus injection of 5000 anti-factor Xa units of low MW heparin given i.v . inhibited fibrin formation , as determined by FPA generation , for up to 4 h and permitted dialysis for 6 h. Such a bolus injection may be useful for short frequent dialyses . Infusion of low MW heparin in the same dosage regimen as unfractionated heparin , 5000 anti-factor Xa units bolus plus 1500 anti-factor Xa units/h , result ed in a progressive rise in heparin , caused by its longer half-life of elimination from the circulation , and almost completely suppressed both FPA generation and fibrin clot formation for 6 h dialysis . From these studies we calculate that infusion of this low MW heparin at a dose of approximately 4000 anti-factor Xa units bolus plus 750 anti-factor Xa units/h should be a useful regimen that will be effective in suppressing fibrin formation during prolonged dialysis , and the plasma anti-factor Xa level of low MW heparin may reflect its ability to inhibit fibrin formation , although exactly comparable anti-factor Xa levels of unfractionated commercial heparin and low MW heparins may not have identical inhibitory effects Ten patients on chronic intermittent hemodialysis treatment received either unfractionated heparin or low molecular weight ( LMW ) heparin K 2165 in a single-blinded r and omized cross-over study to assess : effects on hemostasis and ex vivo platelet functions , and effectiveness , i.e. prevention of fibrin formation in the extracorporeal circuit . The 20 dialysis treatments were without untoward side effects , for both drugs used . The variation in the plasma anti-Xa activities was significantly less during K 2165 treatment than during heparinization . No differences between the drugs were observed regarding the Ivy bleeding time , platelet count and platelet aggregation ( spontaneous , and induced by ADP and collagen ) . Plasma platelet factor 4 levels did not increase under K 2165 to such an extent as under heparin . Both drugs did not influence the plasma levels of beta-thromboglobulin , thromboxane B2 and platelet serotonin content . K 2165 did not affect platelet adhesion to collagen , in contrast to heparin which substantially inhibited platelet adhesion . Under both treatments , 4 minor clots were observed in 4 artificial kidneys , despite plasma anti-Xa levels in between 0.19 and 0.46 U/ml . K 2165 may therefore be considered as effective an anticoagulant as heparin , with less effects on ex vivo platelet functions BACKGROUND Increased platelet reactivity presages adverse cardiac events . Because both haemodialysis and unfractionated heparin ( UFH ) can increase platelet reactivity , we compared platelet reactivity during haemodialysis when patients were anticoagulated with UFH or enoxaparin . METHODS Patients ( n = 20 ) underwent consecutive haemodialysis sessions with either UFH or enoxaparin in a r and om order . Blood was taken from the arterial end of the haemodialysis circuit at the initiation of haemodialysis before anticoagulation . Subsequently , blood was taken during dialysis from the venous end of the circuit 10 min after treatment with UFH or enoxaparin . Platelet reactivity was assessed with the use of flow cytometry by determining the capacity of platelets to bind fibrinogen and the surface expression of P-selectin in response to adenosine diphosphate ( ADP , 0 and 0.2 microM ) . Results were compared with the use of two-way repeated measure ANOVA . RESULTS Platelet reactivity in arterial blood obtained at the beginning of dialysis prior to patients being treated with either UFH [ 0.2 microM ADP-induced capacity to bind fibrinogen = 28+/-15 % ( SD ) ] or enoxaparin ( 30+/-18 % ) was similar ( P = 0.15 ) . In contrast , platelet reactivity was less after treatment with enoxaparin compared with UFH ( P = 0.006 ) . The 0.2 microM ADP-induced capacity to bind fibrinogen in venous blood obtained 10 min after anticoagulation was 34+/-11 % after treatment with UFH and 22+/-11 % after treatment with enoxaparin . CONCLUSIONS Anticoagulation with enoxaparin during haemodialysis is associated with less platelet reactivity compared with UFH . Accordingly , enoxaparin use may contribute to a lesser risk of cardiac events in patients with end-stage renal disease treated with haemodialysis Background : Low-molecular-weight heparins offer several advantages over st and ard heparins , but their use for maintenance hemodialysis has been limited in North America because of their higher cost . Our objective was to compare tinzaparin to st and ard heparin during maintenance hemodialysis over an 8-week period , in regard to the visual aspect of the extracorporeal circuit , filter reuse , bleeding and time for compression of vascular access at the end of hemodialysis session , nursing time devoted to anticoagulation administration , level of satisfaction of patients and nurses , and relative cost . Methods : Thirty-two chronic hemodialysis adult patients with peripheral accesses were r and omly divided into two groups in a cross-over design : tinzaparin for 4 weeks followed by st and ard heparin for 4 weeks , or vice versa . Hemodialysis was performed thrice weekly over 3.5–4 h using large surface reused filters . St and ard heparin was administered as an initial bolus of 50–75 units per kilogram followed by an infusion to maintain an activated clotting time ( ACTESTER ) between 150 and 200 s and discontinued 30–45 min before the end of the session . The initial dose of tinzaparin was 3,500 IU anti-Xa for patients usually receiving 7,500 units or less of st and ard heparin , or 4,500 IU anti-Xa for patients receiving more than 7,500 units of st and ard heparin , and it was injected as a bolus in the arterial line at the beginning of hemodialysis . Dosage adjustments were made by increments or decrements of 500 IU . Results : A total of 6 patients did not require any adjustment in their dose of tinzaparin and remained at the initial dose , while the remaining 26 necessitated adjustments of the initial dose of tinzaparin : 20 patients required increments from the initial dose whereas 6 required reductions . For most patients , 27 of them , the st and ard heparin dose was kept at the same level throughout the study period ( since it was their usual regimen and they were in stable medical conditions ) . According to the monitoring scale , the visual aspects of the tubing of the extracorporeal circuit and of the dialyzers at the end of the session were similar for both tinzaparin and st and ard heparin . The time of compression of the vascular access at the end of the hemodialysis sessions was not significantly different with tinzaparin than with st and ard heparin . However , as indicated below , most patients noted less bleeding ( or oozing ) from their access ( during compression and thereafter , in the few hours after hemodialysis ) with tinzaparin than with st and ard heparin . Clotting was observed more frequently in the arterial and venous bubble traps with tinzaparin than with st and ard heparin . The presence of clot(s ) was observed in the arterial and venous bubble traps in , respectively , 18 ± 12 and 10 ± 6 % of the sessions with tinzaparin , while in , respectively , 3 ± 4 and 2 ± 4 % of the sessions with st and ard heparin ( p < 0.005 ) . Despite a tendency for a reduced reuse number of the dialyzers , the difference did not reach statistical significance . Among the 30 patients who completed the study , 2 reported excessive bleeding from their vascular access with tinzaparin whereas 8 reported such an excessive bleeding with st and ard heparin . The level of satisfaction of patients and nurses for tinzaparin was extremely good . The main reasons stated by the patients was reduced bleeding from their access after dialysis . The nurses preferred tinzaparin because of the simplicity and the rapidity of its administration , the lack of monitoring required , and the decreased bleeding/oozing tendency from the vascular access sites . The time spent for anticoagulation during a hemodialysis session was reported as 5 min with st and ard heparin ( if no ACTESTER monitoring ) , 25–30 min with st and ard heparin ( if ACTESTER monitoring required ) , and 1 min with tinzaparin . The cost analysis revealed that although tinzaparin is more than six times more expensive than st and ard heparin , the use of tinzaparin becomes similar to the use of st and ard heparin ( USD 7.33 vs. USD 7.62 Canadian dollars for one hemodialysis session ) if ACTESTER monitoring is performed ( assuming that 22 % of the sessions are routinely monitored and that one ACTESTER device is necessary for 8–10 dialysis stations , as applied in our unit ) . Conclusion : Our experience with tinzaparin was positive : it represents a simple and easy way to offer anticoagulation during maintenance hemodialysis , it seems associated with less postdialysis bleeding , it saves precious nursing time and is widely appreciated by patients and staff In haemodialysis low-molecular-weight ( LMW ) heparin is increasingly used for anticoagulation . The advantages over unfractionated ( UF ) heparin are the lower bleeding risk and the lack of influence on lipid metabolism . However , no reliable and rapid method is available so far to control the efficacy and safety of LMW heparin during haemodialysis . The specific anti-factor Xa ( aXa ) chromogenic substrate assays are laborious and time consuming . In the present study we have compared chromogenic assay with a coagulation assay ( heptest ) , which was performed from plasma and whole-blood sample s. The effects were compared with unfractionated heparin during haemodialysis . The aXa activity in the chromogenic S2222 assay ranged between 0.2 and Output:	Conclusions . LMWH is as safe and effective as UFH .
MS21659	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Obesity and type 2 diabetes ( T2D ) are associated with abnormal cardiovascular autonomic function and increased risk for cardiac complications , especially after exercise . Since improvements at rest are not always observed after training , we investigated changes in resting and post-exercise autonomic function in obese women with and without T2D after16-week of walking training . Heart rate ( HR ) variability ( HRV ) and baroreflex sensitivity ( BRS ) were measured at rest and 20 min after a 20 min bout of treadmill exercise at 65 % VO2 peak in obese women with ( n = 8) and without T2D ( n = 12 ) before and after training . HRV was analyzed by frequency-domain [ high- ( HF ) power and low-frequency ( LF ) ] and BRS by the sequence method . Exercise training induced similar significant changes in VO2 peak , resting systolic blood pressure ( SBP ) and post-exercise autonomic function in both groups . Training increased VO2 peak ( 6 % ; P < 0.01 ) and decreased resting SBP ( 8 % ; P < 0.001 ) . Increased post-exercise HR recovery ( 5 % ; P < 0.001 ) , HF power ( 14 % ; P < 0.05 ) , LF power ( 14 % ; P < 0.05 ) and BRS ( 86 % ; P < 0.001 ) were also observed . Resting autonomic function and post-exercise SBP were not altered after training . In conclusion , endurance training reduced blood pressure without changes in HRV and BRS at rest , but training increased HRV and BRS during the recovery of acute endurance exercise indicating an improved post-exercise autonomic modulation of HR , which was similar in obese women with and without T2D Aims /hypothesisGait characteristics and balance are altered in diabetic patients . Little is known about possible treatment strategies . This study evaluates the effect of a specific training programme on gait and balance of diabetic patients . Methods This was a r and omised controlled trial ( n = 71 ) with an intervention ( n = 35 ) and control group ( n = 36 ) . The intervention consisted of physiotherapeutic group training including gait and balance exercises with function-orientated strengthening ( twice weekly over 12 weeks ) . Controls received no treatment . Individuals were allocated to the groups in a central office . Gait , balance , fear of falls , muscle strength and joint mobility were measured at baseline , after intervention and at 6-month follow-up . Results The trial is closed to recruitment and follow-up . After training , the intervention group increased habitual walking speed by 0.149 m/s ( p < 0.001 ) compared with the control group . Patients in the intervention group also significantly improved their balance ( time to walk over a beam , balance index recorded on Biodex balance system ) , their performance-oriented mobility , their degree of concern about falling , their hip and ankle plantar flexor strength , and their hip flexion mobility compared with the control group . After 6 months , all these variables remained significant except for the Biodex sway index and ankle plantar flexor strength . Two patients developed pain in their Achilles tendon : the progression for two related exercises was slowed down . Conclusions /interpretationSpecific training can improve gait speed , balance , muscle strength and joint mobility in diabetic patients . Further studies are needed to explore the influence of these improvements on the number of reported falls , patients ’ physical activity levels and quality of life . Trial registration : Clinical Trials.gov NCT00637546 Funding : This work was supported by the Swiss National Foundation ( SNF ) : Objective : The objective of this study was to eluci date whether the degree of autonomic modulation is associated with the degree of microvascular complications in patients with type 1 diabetes . Methods : A total of 290 type 1 individuals with diabetes were r and omly recruited during normal visits to outpatient clinics at 4 Danish hospitals . The degree of autonomic modulations was quantified by measuring heart rate variability ( HRV ) during passive spectral analysis and active tests ( valsalva ratio [ VT ] , response to st and ing [ RT ] , and deep breathing [ E : I ] ) . To describe possible associations between severity of microvascular complications and measures of autonomic modulation , multivariate analysis was performed . Results : After adjusting for diabetes duration , sex , age , pulse pressure , heart rate , and smoking , autonomic dysfunction remained significantly correlated with severity of retinopathy , nephropathy , and peripheral neuropathy in individuals with type 1 diabetes patients . Conclusions : Autonomic dysfunction is present in early stages of retinopathy , nephropathy , and peripheral neuropathy in patients with type 1 diabetes BACKGROUND Diabetes is the most important cause of peripheral neuropathy ( DPN ) . No definitive treatment for DPN has been established , and very few data on the role of exercise training on DPN have been reported . AIM OF THE STUDY We sought to examine the effects of long-term exercise training on the development of DPN in both Types 1 and 2 diabetic patients . PARTICIPANTS AND METHODS Seventy-eight diabetic patients without signs and symptoms of peripheral DPN were enrolled , r and omized , and subdivided in two groups : 31 diabetic participants [ 15 f , 16 m ; 49+/-15.5 years old ; body mass index ( BMI ) = 27.9+/-4.7 ] , who performed a prescribed and supervised 4 h/week brisk walking on a treadmill at 50 % to 85 % of the heart rate reserve ( exercise group : EXE ) , and a control group of 47 diabetic participants ( CON ; 24 f , 23 m ; 52.9+/-13.4 years old ; BMI = 30.9+/-8.4 ) . Vibration perception threshold ( VPT ) , nerve distal latency ( DL ) , nerve conduction velocity ( NCV ) , and nerve action potential amplitude ( NAPA ) in the lower limbs were measured . RESULTS We found significant differences on Delta ( delta ) in NCV for both peroneal and sural motor nerve between the EXE and CON groups during the study period ( P<.001 , for both ) . The percentage of diabetic patients that developed motor neuropathy and sensory neuropathy during the 4 years of the study was significantly higher in the CON than the EXE group ( 17 % vs. 0.0 % , P<.05 , and 29.8 % vs. 6.45 % , P<.05 , respectively ) . In addition , the percentage of diabetic patients who developed increased VPT ( 25 V ) during the study was significantly higher in the CON than the EXE group ( 21.3 % vs. 12.9 % , P<.05 ) . Change on Hallux VPT from baseline to the end of the study was significantly different between the EXE and CON groups ( P<.05 ) ; no significant change in Malleolus VPT between the two groups occurred . CONCLUSIONS This study suggests , for the first time , that long-term aerobic exercise training can prevent the onset or modify the natural history of DPN Background Low heart rate variability ( HRV ) is associated with a higher risk of death in patients with heart disease and in elderly subjects and with a higher incidence of coronary heart disease ( CHD ) in the general population . Methods and Results We studied the predictive value of HRV for CHD and death from several causes in a population study of 14 672 men and women without CHD , aged 45 to 65 , by using the case-cohort design . At baseline , in 1987 to 1989 , 2-minute rhythm strips were recorded . Time-domain measures of HRV were determined in a r and om sample of 900 subjects , for all subjects with incident CHD ( 395 subjects ) , and for all deaths ( 443 subjects ) that occurred through 1993 . Relative rates of incident CHD and cause-specific death in tertiles of HRV were computed with Poisson regression for the case-cohort design . Subjects with low HRV had an adverse cardiovascular risk profile and an elevated risk of incident CHD and death . The increased risk of death could not be attributed to a specific cause and could not be explained by other risk factors . Conclusions Low HRV was associated with increased risk of CHD and death from several causes . It is hypothesized that low HRV is a marker of less favorable health Heart rate ( HR ) variability has been extensively studied in patients surviving an acute myocardial infa rct ion ( AMI ) . The majority of studies have shown that patients with reduced or abnormal HR variability/turbulence have an increased risk of mortality within few years after an AMI . Various measures of HR dynamics , such as time-domain , spectral , and non-linear measures of HR variability , as well as HR turbulence , have been used in risk stratification of post-AMI patients . The prognostic power of various measures , except of those reflecting rapid R – R interval oscillations , has been almost identical , albeit some non-linear HR variability measures , such as short-term fractal scaling exponent , and HR turbulence , have provided somewhat better prognostic information than the others . Abnormal HR variability predicts both sudden and non-sudden cardiac death after AMI . Because of remodeling of the arrhythmia substrate after AMI , early measurement of HR variability to identify those at high risk should likely be repeated later in order to assess the risk of fatal arrhythmia events . Future r and omized trials using HR variability/turbulence as one of the pre-defined inclusion criteria will show whether routine measurement of HR variability/turbulence will become a routine clinical tool for risk stratification of post-AMI patients BACKGROUND Heart rate variability ( HRV ) reflects autonomic nervous system modulation of cardiac activity . There is a relationship between degrees of physical activity , HRV changes and the risk of cardiovascular disease . AIM To study the effect of a supervised integrated exercise programme on HRV in type 2 diabetes mellitus ( DM ) . METHODS The study group consisted of 48 patients ( 27 males , mean age 62+/-7 years ) with type 2 diabetes , of whom 28 underwent a special exercise programme whereas the remaining 20 did not and served as the control group . The supervised integrated exercise programme was applied for a period of 9 months . Deep breathing time domain HRV ( difference between the shortest and the longest R-R interval over one minute ) was measured at baseline and after 3 , 6 and 9 months . RESULTS A significant improvement in the HRV values was observed with increasing duration of exercise ( 13.03+/-1.08 beats/min at baseline versus 16.5+/-1.11 beats/min at 9 months , p < 0.001 ) whereas HRV decreased in the control group ( 14.85+/-1.15 beats/min at baseline vs. 14.30+/-1.75 at 9 months , p < 0.05 ) . Favourable changes in HRV in the exercise group were gender-dependent and were significant in males ( 12.4+/-1.76 beats/min at baseline vs. 16.18+/-1.91 at 9 months , p < 0.001 ) whereas in females only a trend towards HRV improvement was observed . The HRV changes were also age-dependent and were more pronounced in younger patients than in the elderly . The metabolic parameters of diabetes control ( blood glucose and glycosylated haemoglobin levels ) significantly improved in the exercise group and significantly worsened in the control group . CONCLUSIONS Regular supervised integrated exercise significantly improves HRV in patients with type 2 DM , which may favourably influence their long-term prognosis [ Purpose ] This study evaluated the effects of 12 weeks combined aerobic and resistance exercise on heart rate variability in patients with Type 2 diabetes mellitus . [ Subjects and Methods ] The subjects were 16 female patients with Type 2 diabetes mellitus selected among the participants of a chronic disease management exercise class at C Region Public Health Center in South Korea . Subjects were r and omly assigned to the exercise group ( n=8 ; age , 55.97 ± 7.37 ) or the control group ( n=8 ; age , 57.53 ± 4.63 ) The exercise group performed aerobic and resistance exercises for 60 minutes per day , 3 times per week for 12 weeks . Anthropometric measurements , biochemical markers , physical fitness , and heart rate variability were examined . [ Results ] After 12 weeks of exercise , weight , body fat percentage , waist circumference , blood glucose , insulin resistance , glycated hemoglobin level , systolic blood pressure , and diastolic blood pressure significantly decreased and cardiorespiratory fitness and muscular strength significantly increased in the exercise group . Although heart rate variability measures showed favorable changes with the exercise program , none were significant . [ Conclusion ] Although the exercise program did not show notable changes in heart rate variability in patients with Type 2 diabetes within the timeframe of the study , exercise may contribute to the prevention and control of cardiovascular autonomic neuropathy Autonomic neuropathy in diabetes leads to impaired regulation of blood pressure and heart rate variability ( HRV ) , which is due to a shift in cardiac autonomic balance towards sympathetic dominance . Lower HRV has been considered a predictor of cardiac mortality and morbidity . Deep breathing test is a simple method to measure HRV and it provides a sensitive measure of cardiac autonomic function . The effect of long-term physical activity on HRV in type-2 diabetes mellitus is inconclusive . We aim ed to evaluate the effects of regular physical exercise on HRV with Output:	Physical exercise has become a therapy for T2DM , because it improves physical fitness and functional capacity , enhances metabolic control and insulin sensitivity , reduces inflammatory markers and neuropathy symptoms and can increase the regenerative capacity of cutaneous axons , slowing or preventing neuropathy progression . However , it is not clear to what extent physical exercise can improve HRV in this population . Weekly frequency might be the most important factor to improve HRV . These aspects could help to design better programs based in scientific evidence , incorporating HRV as an important variable associated with diabetic neuropathy and mortality
MS21660	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective The goal of this study was to evaluate clinical ly the acceptability of the IDAS II ( Intelligent Drug Administration System ) , a new electronic device that enables drug adherence monitoring . Methods IDAS II was compared to another electronic monitor , the Medication Event Monitoring System ( MEMS ) in a r and omised two-way cross-over study involving 24 hypertensive patients treated with irbesartan . Patients used each device for 2 months . The main parameter of evaluation was the patients ’ opinion on both devices . Rates of adherence and blood pressure were also assessed . Results Most patients considered both devices to be reliable reminders ( IDAS II : 75%;MEMS : 84 % , p = ns ) . Ten patients ( 42 % ) preferred the MEMS , while 11 ( 46 % ) preferred the IDAS II ; three ( 12 % ) expressed no preference . Patients found the MEMS device easier to use than the IDAS device ( p < 0.001 ) but appreciated the IDAS blister packs better than the MEMS bulk packaging ( p < 0.01 ) . Over the 4-month period , the median “ taking adherence ” was excellent ( 99.2 % ) and comparable with both devices . However , the regularity of drug intake timing was higher with the IDAS II ( p < 0.01 ) . Conclusion IDAS II , a new electronic device enabling drug adherence monitoring without reconditioning of the drugs appears to be a well-accepted device . Overall , practicability and acceptability of the IDAS II and the MEMS device were similar . Thus , IDAS II could be a useful tool for the management of long-term therapies OBJECTIVE To examine the extent to which district health teams could reduce the burden of malaria , a continuing major cause of mortality and morbidity , in a situation where severe re source constraints existed and integrated care was provided . METHODS Antimalarial drugs were prepackaged into unit doses in an attempt to improve compliance with full courses of chemotherapy . FINDINGS Compliance improved by approximately 20 % in both adults and children . There were 50 % reductions in cost to patients , waiting time at dispensaries and drug wastage at facilities . The intervention , which tended to improve both case and drug management at facilities , was well accepted by health staff and did not involve them in additional working time . CONCLUSION The prepackaging of antimalarials at the district level offers the prospect of improved compliance and a reduction in the spread of resistance Outpatient medication adherence is a major problem , especially for patients repeatedly hospitalized for psychiatric disorders . This study included 39 such patients who were receiving case management services from a community mental health center . Patients were matched and r and omly assigned to receive in a single session either ( 1 ) information regarding medication and its benefits , ( 2 ) guidelines for assuring adherence which encompassed all phases related to pill-taking including filling prescriptions , use of a pill container , transportation , self-reminders , doctor 's appointments and so forth , or ( 3 ) the same guidelines as ( 2 ) above but given in the presence of a family member who was enlisted in support . The results showed that adherence increased to about 94 % after the guidelines were given for both the individual and family guideline procedure , whereas adherence remained unchanged at 73 % after the medication information procedure . These results suggest a practical means for assuring a high level of medication adherence for patients with psychiatric disorders We investigated the impact of pre-packaging antimalarial drugs and counselling on compliance with treatment of malaria at the Adult Outpatient Department of Port Moresby General Hospital . Adult patients who were prescribed st and ard antimalarial drugs following clinical and microscopic diagnosis of malaria were r and omly assigned to one of three groups : an intervention group , where pre-packaging and counselling instructions were applied ; control group A , with counselling but no pre-packaging ; and control group B , with neither counselling nor pre-packaging . Patients were interviewed on two occasions , day 1 of treatment and day 4 post treatment . Of a total of 436 patients , 322 patients ( 179 males and 143 females ) completed the study . Our data indicate an increase of 18 % in compliance with treatment in the intervention group and 16 % in control group A , when compared with control group B. While compliance with treatment was gender independent , the language spoken and used for giving instructions and counselling may have influenced patients ' behaviour on prescribed medication . The results of our study indicate that a simple pre-packaging system and proper counselling could improve compliance with antimalarial drug treatment . As an additional beneficial observation , pre-packaging is likely to eliminate errors and possible contamination of the products during dispensing Abstract Objective To determine whether home based medication review by pharmacists affects hospital readmission rates among older people . Design R and omised controlled trial . Setting Home based medication review after discharge from acute or community hospitals in Norfolk and Suffolk . Participants 872 patients aged over 80 recruited during an emergency admission ( any cause ) if returning to own home or warden controlled accommodation and taking two or more drugs daily on discharge . Intervention Two home visits by a pharmacist within two weeks and eight weeks of discharge to educate patients and carers about their drugs , remove out of date drugs , inform general practitioners of drug reactions or interactions , and inform the local pharmacist if a compliance aid is needed . Control arm received usual care . Main outcome measure Total emergency readmissions to hospital at six months . Secondary outcomes included death and quality of life measured with the EQ-5D . Results By six months 178 readmissions had occurred in the control group and 234 in the intervention group ( rate ratio = 1.30 , 95 % confidence interval 1.07 to 1.58 ; P = 0.009 , Poisson model ) . 49 deaths occurred in the intervention group compared with 63 in the control group ( hazard ratio = 0.75 , 0.52 to 1.10 ; P = 0.14 ) . EQ-5D scores decreased ( worsened ) by a mean of 0.14 in the control group and 0.13 in the intervention group ( difference = 0.01 , -0.05 to 0.06 ; P = 0.84 , t test ) . Conclusions The intervention was associated with a significantly higher rate of hospital admissions and did not significantly improve quality of life or reduce deaths . Further research is needed to explain this counterintuitive finding and to identify more effective methods of medication review BACKGROUND type 2 diabetes mellitus continues to increase in prevalence worldwide . Many factors have been cited as contributing to compliance , such as family and social support , education , number of tablets per dose , frequency of administration and health care provider communication . Toward these goals , the present study was developed to measure the effect offactors on glycemic control such as diabetes education by pharmacists , a diabetes disease booklet and special medication containers . MATERIAL AND METHOD A total of 360 volunteers with type 2 DM patients were recruited , participants were simple r and omized to control 180 and intervention 180 patients . Which intervention categorized to 4 groups ; all intervention groups received diabetes drug counseling by a pharmacist , one group received plus a diabetes booklet , one received plus special medical containers and the last group received all of them . The interventions were done at the 1st time of visit . Both the control and intervention groups were monitored for fasting plasma glucose and HbA1c at 0 , 3 , 6 months and glycemic level in both groups was compared . RESULTS After 3 months , mean fasting plasma glucose and HbA1c decreased wiih the intervention group vs. control group ( 152.36 + /- 39.73 to 131.52 + /- 35.22 mg% ) and ( 150.16 + /- 41.78 to 153.98 + /- 47.95 mg% ) respectively ; ( p < 0.001 ) . HbA1c level 8.16 + /- 1.44 to 7.72 + /- 1.26 vs 8.01 + /- 1.51 to 8.38 + /- 1.46 respectively ; ( p < 0.001 ) . After 6 months , mean fasting plasma glucose and HbA1c decreased with the intervention group vs. control group ( 152.36 + /- 39.73 to 145.20 + /- 46.07 mg% ) and ( 150.16 + /- 41.78 to 159.16 + /- 54.90 mg% ) respectively ; ( p < 0.013 ) . HbA1c level 8.16 + /- 1.44 to 7.91 + /- 1.27 vs. 8.01 + /- 1.51 to 8.80 + /- 1.36 respectively ; ( p < 0.001 ) . The most favorable glycemic outcome was the group that received all of the interventions ; mean FPG was reduced from 147.46 + /- 36.07 to 125.38 + /- 31.12 mg% ( p < 0.000 ) in 1nd visit ( 3 months later ) and still reducing effect on the 2nd visit ( 6 month later ) mean FPG from 147.46 + /- 36.07 to 130.21 + /- 33.96 mg% ( p < 0.016 ) also the same way in HbA 1c level . The group that received only drug counseling by pharmacist had no significant reduction in FPG and HbA1c . ( p > 0.05 ) . CONCLUSION Drug counseling by a pharmacist has little beneficial effect on diabetes management outcome compared to the diabetes booklet and special drug container . To improve glycemic control of type 2 DM is to integrate self-management in daily life , wide a variety of education , drug taken behavior and health care provider available communication produce improvement in patient management and is somewhat better when used in combination CONTEXT Rising costs of medications and inequities in access have sparked calls for drug policy reform in the United States and Canada . Control of drug expenditures by prescription cost-sharing for elderly persons and poor persons is a contentious issue because little is known about the health impact in these subgroups . OBJECTIVES To determine ( 1 ) the impact of introducing prescription drug cost-sharing on use of essential and less essential drugs among elderly persons and welfare recipients and ( 2 ) rates of emergency department ( ED ) visits and serious adverse events associated with reductions in drug use before and after policy implementation . DESIGN AND SETTING Interrupted time-series analysis of data from 32 months before and 17 months after introduction of a prescription coinsurance and deductible cost-sharing policy in Quebec in 1996 . Separate 10-month prepolicy control and postpolicy cohort studies were conducted to estimate the impact of the drug reform on adverse events . PARTICIPANTS A r and om sample of 93 950 elderly persons and 55 333 adult welfare medication recipients . MAIN OUTCOME MEASURES Mean daily number of essential and less essential drugs used per month , ED visits , and serious adverse events ( hospitalization , nursing home admission , and mortality ) before and after policy introduction . RESULTS After cost-sharing was introduced , use of essential drugs decreased by 9.12 % ( 95 % confidence interval [ CI ] , 8.7%-9.6 % ) in elderly persons and by 14.42 % ( 95 % CI , 13.3%-15.6 % ) in welfare recipients ; use of less essential drugs decreased by 15.14 % ( 95 % CI , 14.4%-15.9 % ) and 22.39 % ( 95 % CI , 20.9%-23.9 % ) , respectively . The rate ( per 10 000 person-months ) of serious adverse events associated with reductions in use of essential drugs increased from 5.8 in the prepolicy control cohort to 12.6 in the postpolicy cohort in elderly persons ( a net increase of 6.8 [ 95 % CI , 5.6 - 8.0 ] ) and from 14.7 to 27.6 in welfare recipients ( a net increase of 12.9 [ 95 % CI , 10.2 - 15.5 ] ) . Emergency department visit rates related to reductions in the use of essential drugs also increased by 14.2 ( 95 % CI , 8.5 - 19.9 ) per 10 000 person-months in elderly persons ( prepolicy control cohort , 32.9 ; postpolicy cohort , 47.1 ) and by 54.2 ( 95 % CI , 33.5 - 74.8 ) among welfare recipients ( prepolicy control cohort , 69.6 ; postpolicy cohort , 123.8 ) . These increases were primarily due to an increase in the proportion of recipients who reduced their use of essential drugs . Reductions in the use of less essential drugs were not associated with an increase in risk of adverse events or ED visits . CONCLUSIONS In our study , increased cost-sharing for prescription drugs in elderly persons and welfare recipients was followed by reductions in use of essential drugs and a higher rate of serious adverse events and ED visits associated with these reductions OBJECTIVE To examine the relationship between adherence to a medical regimen and mortality following a myocardial infa rct ion in women . DESIGN Analysis of the female cohort entered into a r and omized double-blind multicenter trial . SETTING National Heart , Lung , and Blood Institute Output:	Reminder packing may represent a simple method for improving adherence for patients with selected conditions .
MS21661	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Dental caries remains a major public health problem , especially for certain high-risk population groups . The goal of this study was to assess the evidence regarding strategies meant to be used as alternatives or booster/supplements to fluoride for caries prevention and management . Articles were selected for inclusion if they had a prospect i ve longitudinal design , with a fluoride control arm , and were conducted in human subjects . Of the included studies , 7/18 studies on calcium-based strategies favored the test product ( the majority of studies included exposure of fluoride in all groups ) . All the arginine studies ( 8/8 ) included a combination of arginine and a calcium base , and concluded that this has the potential to significantly boost the performance of fluoride . The remaining included studies focused on the addition of microbial-related strategies to a fluoride-containing vehicle ( 2 xylitol studies and 1 study using a probiotic milk ) , and all favored the combination as a booster to fluoride . Thus , the current study did not identify evidence for any strategy to effectively be used as a substitute or alternative to fluoride , but identified some consistent evidence derived from the use of prebiotic strategies ( primarily from use of arginine combined with calcium ) to support their potential use to boost the mechanism of action of fluoride . Thus , fluoride-based strategies remain the st and ard for caries prevention and management , with some evidence that boosting the effects of fluoride by the use of prebiotic strategies is a promising possibility Objective : Considering the minimally invasive approach to dentistry , the scientific community has focused on non-invasive treatments for caries lesions . The aim of this study was to evaluate the efficacy of a nonsurgical approach to arrest occlusal non-cavitated dentin lesions through glass ionomer sealing . Methods : In this controlled clinical trial , 51 teeth with clinical ly non-cavitated occlusal caries radiographically located beneath the enamel-dentine junction ( radiolucent area ) were selected among patients presenting a moderate to high risk of caries . The teeth were r and omly divided into two groups : an experimental group receiving an application of Vidrion-R ( SS White ) glass ionomer and a control group not su bmi tted to any clinical intervention . Caries progression was monitored by clinical and radiographic examination at 4-monthly intervals over a period of one year . In addition , marginal integrity of the sealant was evaluated in the experimental group . Results : Clinical examination showed no statistical difference between the groups ( P=.13 ) . On the other h and , sealed teeth presented lower caries progression when analyzed by radiographic examination ( P=.004 ) . Conclusion : A glass ionomer sealant over non-cavitated occlusal caries lesions in dentin may not be sufficiently effective in arresting their progression Concern about the survival of microorganisms in deep carious lesions may often lead to unnecessary exposure of the pulp during final excavation . There are reasons , therefore , to initiate systematic studies on the alternative procedure known as stepwise excavation . Clinical evaluation of stepwise excavation was performed on 31 deep carious lesions considered to result in pulp perforation by traditional excavation . This study examines the clinical and microbiological alterations during the final excavation performed during long intervals ( 6 - 12 months ) after the initial treatment that included peripheral dentine excavation and removal of the central cariogenic biomass and the superficial necrotic dentine . The dentine colour and consistency were assessed by means of st and ardized scales before application of a Ca(OH)2 compound and a temporary sealing for 6 - 12 months . Re assessment s were performed before the after final excavation . Microbiological dentine sample s were obtained in 19 r and omly selected lesions by a sterile bur , transferred to and diluted in reduced transport fluid , and plated on tryptic soy agar . After anaerobic incubation at 37 degrees C for 7 days , total colony-forming units per millilitre were counted from ( 1 ) peripheral excavated and hard dentine ( control ) , ( 2 ) central demineralized dentine before and final excavation , and ( 3 ) central dentine after the final excavation . Six sample s of central demineralized dentine were without any cultivable flora increasing to 9 sample s after the final excavation . The clinical dentine changes occurring during stepwise excavation were characterized by enhanced hardness of the dentine which was associated with a marked reduction in bacterial growth after the final excavation . Despite the presence of bacteria in the excavated dentine none of the carious lesions result ed in pulp perforation , suggesting that the initial removal of the cariogenic biomass appears to be essential for control of caries progression . Stepwise excavation is not only an appropriate treatment of deep carious lesions but is also considered a suitable model for microbiological studies to determine the bacteria persisting in clinical ly excavated lesions OBJECTIVE The objective of this study was to assess radiographic outcomes after partial carious dentin removal performed in deep caries lesions over a 10-year period . STUDY DESIGN Baseline image was compared to 3 follow-up radiographs ( at 6 - 7 months , 3 years , and 10 years ) . Tertiary dentin deposition and lesion depth were qualitatively assessed . Radiographic density changes in the radiolucent zone ( RZ ) beneath the restoration were quantitatively compared to the control areas ( CA ) using digital subtraction radiography ( Friedman repeated- measures analysis of variance ) . RESULTS A total of 13 teeth were evaluated . In most cases , lesion depth remained unchanged or decreased ( 12/13 ) and tertiary dentin formation was observed ( 10/13 ) after the 10-year follow-up . Differences between RZ and CA at the 6- to 7-month and 3-year follow-up periods were similar but significantly lower than those at the 10-year assessment . CONCLUSIONS Sealing of carious dentin arrested the caries process , promoted deposition of tertiary dentin , and induced mineral gain in the radiolucent zone PURPOSE To follow-up teeth with deep caries lesions su bmi tted to incomplete caries removal over a 10-year period . METHODS 27 subjects ( 32 permanent posterior teeth ) with deep caries lesions composed the sample . In this single-arm long-term prospect i ve study , the inclusion criteria were risk of pulp exposure during caries excavation , positive response to the cold test , absence of spontaneous pain or sensitivity during percussion , and radiographic absence of a periapical lesion . Subjects were su bmi tted to the following procedures : complete caries removal from the surrounding cavity walls , incomplete caries removal from the pulpal wall , capping with a calcium hydroxide cement , and sealing with a modified zinc oxide-eugenol cement . After 6 - 7 months , the temporary sealing was removed for method ological purpose s ( no further excavation was performed ) , and teeth were capped with a calcium hydroxide cement and filled with resin composite . Clinical and radiographic assessment s were conducted after 6 - 7 months , 1.5 , 3 , 5 and 10 years . Success was defined as clinical and radiographic signs and symptoms of pulp sensitivity while failure was defined as endodontic treatment need . RESULTS Over 10 years , one tooth was excluded from the sample ( pulp exposure during treatment ) , five were lost to recall , 10 had therapy failure ( five fractures and four necroses leading to endodontic treatment need , and one extraction ) and 16 had therapy success ( pulp sensitivity ) . Overall survival rates were 97 % , 90 % , 82 % and 63 % at 1.5- , 3- , 5- and 10-year follow-ups , respectively . Teeth with two or more restored surfaces failed significantly more than teeth with one restored surface ( P= 0.01 ) Less invasive excavation methods have been suggested for deep caries lesions . We tested the effects of stepwise vs. direct complete excavation , 1 yr after the procedure had been carried out , in 314 adults ( from six centres ) who had received treatment of a tooth with deep caries . The teeth had caries lesions involving 75 % or more of the dentin and were central ly r and omized to stepwise or direct complete excavation . Stepwise excavation result ed in fewer pulp exposures compared with direct complete excavation [ difference : 11.4 % , 95 % confidence interval ( CI ) ( 1.2 ; 21.3 ) ] . At 1 yr of follow-up , there was a statistically significantly higher success rate with stepwise excavation , with success being defined as an unexposed pulp with sustained pulp vitality without apical radiolucency [ difference : 11.7 % , 95 % CI ( 0.5 ; 22.5 ) ] . In a subsequent nested trial , 58 patients with exposed pulps were r and omized to direct capping or partial pulpotomy . We found no significant difference in pulp vitality without apical radiolucency between the two capping procedures after more than 1 yr [ 31.8 % and 34.5 % ; difference : 2.7 % , 95 % CI ( -22.7 ; 26.6 ) ] . In conclusion , stepwise excavation decreases the risk of pulp exposure compared with direct complete excavation . In view of the poor prognosis of vital pulp treatment , a stepwise excavation approach for managing deep caries lesions is recommended BACKGROUND More conservative techniques for managing dental caries including ' partial ' and ' no caries removal ' have been increasingly of interest . AIM To compare children 's behaviour and pain perception , also technique acceptability ( parents and dentists ) , when approximal dentinal lesions ( ICDAS 3 - 5 ) in primary molars ( 3 - 8-year-olds ) were managed with three treatment strategies ; conventional restorations ( CR ) , hall technique ( HT ) , and non-restorative caries treatment ( N RCT ) . DESIGN Secondary care-based , three-arm parallel-group , r and omised controlled trial , with 169 participants treated by 12 dentists . OUTCOME MEASURES child 's pain perception ( Visual Analogue Scale of Faces ) ; behaviour ( Frankl scale ) ; and parents ' and dentists ' treatment opinions ( 5-point Likert scales ) . RESULTS Children showed more negative behaviour in the CR group ( 37 % ) compared to N RCT ( 21 % ) and HT ( 13 % ) ( P = 0.047 , CI = 0.41 to 0.52 ) . Pain intensity was rated ' very low ' or ' low ' in 88 % N RCT , 81 % HT , and 72 % CR ( P = 0.11 , CI = 0.10 to 0.12 ) . N RCT and HT were ' very easy ' or ' easy ' to perform for > 77 % of dentists , compared to 50 % in CR group ( P < 0.000 ) . There were no statistically significant differences in parents ' rating of their child 's level of comfort ( P = 0.46 , CI = 0.45 to 0.48 ) . CONCLUSIONS Dentists reported more negative behaviour in CR group . For all techniques , children 's pain perception and dentist/parent acceptability were similar OBJECTIVE To evaluate the clinical performance of atraumatic restorative treatment ( ART ) fillings using Fuji IX as a filling material in field conditions . DESIGN Longitudinal study of the ART fillings in permanent teeth of primary school children aged eight to fifteen years . SETTING Primary schools in Morogoro municipality , Tanzania . SUBJECTS AND METHODS St and ard 3 and 4 children in five primary schools r and omly selected from a list of 36 primary schools of Morogoro municipality were examined for dental caries and periodontal conditions . All 296 carious lesions that were indicated for restoration were treated using ART approach according to the instructions given in the manual for ART approach for the control of dental caries . Essential measurements for treated teeth and cavity were taken . The cavities were filled with Fuji IX glass ionomer cement as per manufacturer 's instructions . After one year , 238 restorations were evaluated using the criteria for evaluating ART restorations . MAIN OUTCOME MEASURE Clinical appearance of the surface of the restorations . RESULTS Ninety four per cent of the restorations evaluated were rated as good and intact , while 1.7 % were rated as having slight defects that needed no repair , giving a one year survival rate of 96.1 % . Mean working time was 14.5 minutes . CONCLUSIONS AND RECOMMENDATIONS The one-year survival rate of 96.1 % is high enough to recommend wide use of ART in Tanzania . Town and municipal councils should be encouraged to adopt ART in their school oral health programmes Resin infiltration is an innovative approach to arrest progression of caries lesions . The aim of this r and omized split-mouth placebo-controlled clinical trial was to assess whether resin infiltration of proximal lesions is more effective than non-operative measures alone with respect to the inhibition of caries progression . In 22 young adults , 29 pairs of interproximal lesions with radiological extension into the inner half of enamel or the outer third of dentin were r and omly allocated to two treatment groups . In the test group , lesions were infiltrated ( Icon , pre-product ; DMG ) . A placebo treatment was performed in the control group . All participants received instructions for diet , flossing , and fluoridation . The primary outcome after 18 months was radiographic lesion progression ( assessed by digital subtraction radiography ) . No unwanted effects could be observed . In the effect group , 2/27 lesions ( 7 % ) and in the control group 10/27 lesions ( 37 % ) showed progression ( p = 0.021 ; McNemar ) . Infiltration of interproximal car Output:	For non-cavitated lesions , the use of sealants is supported by strong evidence , while the evidence for infiltration of proximal lesions is moderate . The use of the ART technique to restore cavitated lesions is also supported by strong evidence as a suitable strategy that has been used extensively in the literature concerning non-dental setting s. Preservation of tooth structure through the use of MI treatment for both non-cavitated and cavitated lesions is supported by moderatestrong evidence , which supports the paradigm shift towards routine use of more conservative strategies in the treatment of carious lesions
MS21662	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : An emerging field of research indicates that physical activity can benefit cognitive functions and academic achievements in children . However , less is known about how academic achievements can benefit from specific types of motor activities ( e.g. , fine and gross ) integrated into learning activities . Thus , the aim of this study was to investigate whether fine or gross motor activity integrated into math lessons ( i.e. , motor-enrichment ) could improve children 's mathematical performance . Methods : A 6-week within school cluster-r and omized intervention study investigated the effects of motor-enriched mathematical teaching in Danish preadolescent children ( n = 165 , age = 7.5 ± 0.02 years ) . Three groups were included : a control group ( CON ) , which received non-motor enriched conventional mathematical teaching , a fine motor math group ( FMM ) and a gross motor math group ( GMM ) , which received mathematical teaching enriched with fine and gross motor activity , respectively . The children were tested before ( T0 ) , immediately after ( T1 ) and 8 weeks after the intervention ( T2 ) . A st and ardized mathematical test ( 50 tasks ) was used to evaluate mathematical performance . Furthermore , it was investigated whether motor-enriched math was accompanied by different effects in low and normal math performers . Additionally , the study investigated the potential contribution of cognitive functions and motor skills on mathematical performance . Results : All groups improved their mathematical performance from T0 to T1 . However , from T0 to T1 , the improvement was significantly greater in GMM compared to FMM ( 1.87 ± 0.71 correct answers ) ( p = 0.02 ) . At T2 no significant differences in mathematical performance were observed . A subgroup analysis revealed that normal math-performers benefitted from GMM compared to both CON 1.78 ± 0.73 correct answers ( p = 0.04 ) and FMM 2.14 ± 0.72 correct answers ( p = 0.008 ) . These effects were not observed in low math-performers . The effects were partly accounted for by visuo-spatial short-term memory and gross motor skills . Conclusion : The study demonstrates that motor enriched learning activities can improve mathematical performance . In normal math performers GMM led to larger improvements than FMM and CON . This was not the case for the low math performers . Future studies should further eluci date the neurophysiological mechanisms underlying the observed behavioral effects The aim was to study long-term effects on motor skills and school performance of increased physical education ( PE ) . All pupils born 1990 - 1992 from one school were included in a longitudinal study over nine years . An intervention group ( n = 129 ) achieved daily PE ( 5 × 45 min/week ) and if needed one extra lesson of adapted motor training . The control group ( n = 91 ) had PE two lessons/week . Motor skills were evaluated by the Motor Skills Development as Ground for Learning observation checklist and school achievements by marks in Swedish , English , Mathematics , and PE and proportion of pupils who qualified for upper secondary school . In school year 9 there were motor skills deficits in 7 % of pupils in the intervention group compared to 47 % in the control group ( P < 0.001 ) , 96 % of the pupils in the intervention group compared to 89 % in the control group ( P < 0.05 ) qualified for upper secondary school . The sum of evaluated marks was higher among boys in the intervention group than in the control group ( P < 0.05 ) . The sum of marks was also higher in pupils with no motor skills deficit than among pupils with motor skills deficits ( P < 0.01 ) , as was the proportion of pupils who qualified for upper secondary school ( 97 % vs 81 % , P < 0.001 ) . Daily PE and adapted motor skills training during the compulsory school years is a feasible way to improve not only motor skills but also school performance and the proportion of pupils who qualify for upper secondary school BACKGROUND Perceptual-motor skills contribute to a variety of basic learning skills associated with normal academic success . This study aim ed to determine the relationship between academic performance and perceptual-motor skills in first grade South African learners and whether low SES ( socio-economic status ) school type plays a role in such a relationship . METHODS This cross-sectional study of the baseline measurements of the NW-CHILD longitudinal study included a stratified r and om sample of first grade learners ( n = 812 ; 418 boys and 394 boys ) , with a mean age of 6.78 years ± 0.49 living in the North West Province ( NW ) of South Africa . The Beery-Buktenica Developmental Test of Visual-Motor Integration-4 ( VMI ) was used to assess visual-motor integration , visual perception and h and control while the Bruininks Oseretsky Test of Motor Proficiency , short form ( BOT2-SF ) assessed overall motor proficiency . Academic performance in math , reading and writing was assessed with the Mastery of Basic Learning Areas Question naire . Linear mixed models analysis was performed with spss to determine possible differences between the different VMI and BOT2-SF st and ard scores in different math , reading and writing mastery categories ranging from no mastery to outst and ing mastery . A multinomial multilevel logistic regression analysis was performed to assess the relationship between a clustered score of academic performance and the different determinants . RESULTS A strong relationship was established between academic performance and VMI , visual perception , h and control and motor proficiency with a significant relationship between a clustered academic performance score , visual-motor integration and visual perception . A negative association was established between low SES school types on academic performance , with a common perceptual motor foundation shared by all basic learning areas . CONCLUSION Visual-motor integration , visual perception , h and control and motor proficiency are closely related to basic academic skills required in the first formal school year , especially among learners in low SES type schools Changes in cognitive function induced by physical activity have been proposed as a mechanism for the link between physical activity and academic performance . The aim of this study was to investigate if executive function mediated the prospect i ve relations between indices of physical activity and academic performance in a sample of 10-year-old Norwegian children . The study included 1,129 children participating in the Active Smarter Kids ( ASK ) trial , followed over 7 months . Structural equation modeling ( SEM ) with a latent variable of executive function ( measuring inhibition , working memory , and cognitive flexibility ) was used in the analyses . Predictors were objective ly measured physical activity , time spent sedentary , aerobic fitness , and motor skills . Outcomes were performance on national tests of numeracy , reading , and English ( as a second language ) . Generally , indices of physical activity did not predict executive function and academic performance . A modest mediation effect of executive function was observed for the relation between motor skills and academic performance . Trial registration : Clinical trials.gov registry , trial registration number : NCT02132494 BACKGROUND Physical Activity Across the Curriculum ( PAAC ) was a three-year cluster r and omized controlled trial to promote physical activity and diminish increases in overweight and obesity in elementary school children . METHODS Twenty-four elementary schools were cluster r and omized to the Physical Activity Across the Curriculum intervention or served as control . All children in grade s two and three were followed to grade s four and five . Physical Activity Across the Curriculum promoted 90 min/wk of moderate to vigorous intensity physically active academic lessons delivered by classroom teachers . Body Mass Index was the primary outcome , daily Physical activity and academic achievement were secondary outcomes . RESULTS The three-year change in Body Mass Index for Physical Activity Across the Curriculum was 2.0+/-1.9 and control 1.9+/-1.9 , respectively ( NS ) . However , change in Body Mass Index from baseline to 3 years was significantly influenced by exposure to Physical Activity Across the Curriculum . Schools with > or = 75 min of Physical Activity Across the Curriculum/wk showed significantly less increase in Body Mass Index at 3 years compared to schools that had < 75 min of Physical Activity Across the Curriculum ( 1.8+/-1.8 vs. 2.4+/-2.0 , p=0.02 ) . Physical Activity Across the Curriculum schools had significantly greater changes in daily Physical activity and academic achievement scores . CONCLUSIONS The Physical Activity Across the Curriculum approach may promote daily Physical activity and academic achievement in elementary school children . Additionally , 75 min of Physical Activity Across the Curriculum activities may attenuate increases in Body Mass Index We first replicated the data analytic strategy used in Duncan et al. ( 2007 ) with a population -based data set of French-speaking children from Quebec ( Canada ) . Prospect i ve associations were examined between cognitive , attention , and socioemotional characteristics underlying kindergarten school readiness and second grade math , reading , and general achievement . We then extended this school readiness model by including motor skills as an additional element in the prediction equation and exp and ed the original strategy by including classroom engagement . The Montreal Longitudinal-Experimental Preschool Study , featured in Duncan et al. , served as the Canadian reference group . In the replication model , kindergarten cognitive and attention characteristics predicted achievement by the end of 2nd grade . Although inconsistent across outcomes , behavioral problems and skills also emerged as predictors of some aspects of later achievement . Coefficients for kindergarten math skills were largest , followed by attention skills , receptive language skills , attention problems , and behavior . Most coefficients resembled those generated in the initial study . In our extension model , fine motor skills added their significant contribution to the prediction of later achievement above and beyond the original key elements of school readiness . Our extension model confirmed prospect ively associations between kindergarten cognitive , attention , fine motor , and physical aggression characteristics and later achievement and classroom engagement by the end of 2nd grade . Although they comparatively showed better long-term benefits from stronger early attention skills , girls with less kindergarten cognitive skills were more vulnerable than boys with similar deficits when predicting 2nd grade math OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity PURPOSE The purpose of this study was twofold : 1 ) to evaluate the effectiveness of a school-based physical activity intervention , Action Schools ! BC ( AS ! BC ) , for maintaining academic performance in a multiethnic group of elementary children , and 2 ) to determine whether boys and girls ' academic performance changed similarly after participation in AS ! BC . METHODS This was a 16-month cluster r and omized controlled trial . Ten schools were r and omized to intervention ( INT ) or usual practice ( UP ) . One INT school administered the wrong final test , and one UP school grade d their own test , so both were excluded . Thus , eight schools ( six INT , two UP ) were included in the final analysis . Children ( 143 boys , 144 girls ) in grade s 4 and 5 were recruited for the study . We used the Canadian Achievement Test ( CAT-3 ) to evaluate academic performance ( TotScore ) . Weekly teacher activity logs determined amounts of physical activity delivered by teachers to students . Physical activity was determined with the Physical Activity Question naire for Children ( PAQ-C ) . Independent t-tests compared descriptive variables between groups and between boys and girls . We used a mixed linear model to evaluate differences in TotScore at follow-up between groups and between girls and boys . RESULTS Physical activity delivered by teachers to children in INT schools was increased by 47 min x wk(-1 ) ( 139 + /- 62 vs 92 + /- 45 , P < 0.001 ) . Participants attending UP schools had significantly higher baseline TotScores than those attending INT schools . Despite this , there was no significant difference in TotScore between groups at follow-up and between boys and girls at baseline and follow-up . CONCLUSION The AS ! BC model is an attractive and feasible intervention to increase physical activity for students while maintaining levels of academic performance This pilot study examined the influence of participation in a 6-week bimanual coordination program on Grade 5 students ' reading achievement . Twenty Grade 5 students participated in a bimanual activity ( sport stacking ) and were tested whether reading achievement scores Output:	Findings support associations between several components of motor proficiency and academic performance in mathematics and reading . There was evidence that fine motor proficiency was significantly and positively associated with academic performance in mathematics and reading , particularly during the early years of school . Significant positive associations were also evident between academic performance and components of gross motor proficiency , specifically speed and agility , upper-limb coordination , and total gross motor scores . Preliminary evidence from a small number of experimental studies suggests motor skill interventions in primary school setting s may have a positive impact on academic performance in mathematics and /or reading .
MS21663	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Brain temperature appears to be an important factor affecting motor activity , but it is not known to what extent brain temperature increases during prolonged exercise in humans . Cerebral heat exchange was therefore evaluated in seven males during exercise with and without hyperthermia . Middle cerebral artery mean blood velocity ( MCA V(mean ) ) was continuously monitored while global cerebral blood flow ( CBF ) and cerebral energy turnover were determined at the end of the two exercise trials in three subjects . The arterial to venous temperature difference across the brain ( v-aD(temp ) ) was determined via thermocouples placed in the internal jugular vein and in the aorta . The jugular venous blood temperature was always higher than that of the arterial blood , demonstrating that heat was released via the CBF during the normothermic as well as the hyperthermic exercise condition . However , heat removal via the jugular venous blood was 30 + /- 6 % lower during hyperthermia compared to the control trial . The reduced heat removal from the brain was mainly a result of a 20 + /- 6 % lower CBF ( 22 + /- 9 % reduction in MCA V(mean ) ) , because the v-aD(temp ) was not significantly different in the hyperthermic ( 0.20 + /- 0.05 degrees C ) compared to the control trial ( 0.22 + /- 0.05 degrees C ) . During hyperthermia , the impaired heat removal via the blood was combined with a 7 + /- 2 % higher heat production in the brain and heat was consequently stored in the brain at a rate of 0.20 + /- 0.06 J g(-1 ) min(-1 ) . The present results indicate that the average brain temperature is at least 0.2 degrees C higher than that of the body core during exercise with or without hyperthermia The effects of naltrexone-precipitated withdrawal from buprenorphine on behavior and regional cerebral blood flow ( rCBF ) were studied in 11 opiate-dependent patients . Patients initially received buprenorphine , 2 mg sublingually , every day for 7 days . They were then challenged sequentially with placebo and naltrexone , 25 mg orally , before single photon emission computed tomography with technetium-99m-d , l-hexamethyl-propylene amine oxime as tracer . Behavioral ratings of withdrawal severity were made before and after naltrexone/placebo administration . Naltrexone produced significantly greater signs and symptoms of opiate withdrawal than placebo . Analysis of variance revealed no significant regionally specific effect of naltrexone on rCBF ratios . Severity of withdrawal , however , showed a significant negative correlation with rCBF in the anterior cingulate cortex following naltrexone . These results are interesting as the anterior cingulate region has been implicated in the emotional component of pain and in opiate-induced analgesia In a prospect i ve study of the natural development of total cerebral blood flow volume ( CBFV ) , the common , external and internal carotid and vertebral arteries were examined in 94 healthy children and adolescents between 3 and 18 years of age ( sex and age evenly distributed ) using a 7.0-MHz transducer of a computed sonography system . Intravascular flow volumes were calculated with the product of angle-corrected time-averaged flow velocity and the cross-sectional area of the vessel . CBFV was determined as the sum of flow volumes in the internal carotid and vertebral arteries of both sides . CBFV increased significantly between 3 and 6.5 years of age ( from 687 ± 85 to 896 ± 110 ml/min ; age correlation , p ≤ 0.01 ) and declined thereafter ( p ≤ 0.001 ) to a constant level of ∼700 ml/min at 15 years of age . There was no difference in CBFV between sexes . The proportion of bilateral vertebral artery flow volume in total CBFV decreased significantly between the ages of 3 and 18 years ( p ≤ 0.001 ) . As the flow volumes of the external carotid arteries increased markedly from childhood to adulthood , flow volumes of the common carotid arteries were not representative of CBFV . Intrasession test-retest correlation of CBFV was high ( r = 0.89 , p ≤ 0.0001 ) . Reference data for the childhood years presented here and previously described results from healthy adults allow us to outline the natural evolution of CBFV in humans . The reliability of the method has already been demonstrated . Thus , it may now be introduced into clinical application The effects of intravenous amphetamine infusion ( 0.3 mg/kg ) on cerebral blood flow ( CBF ) and measures of autonomic and behavioral arousal were studied in 12 normal male volunteers in a placebo-controlled crossover design . Nonsignificant decreases were seen in CBF ( measured by 133Xe inhalation ) , despite significant increases in autonomic and behavioral arousal . The apparent dissociation of CBF and arousal appears to be compatible with other human experiments suggesting that amphetamine decreases CBF and metabolism , as well as with neurobiological findings on the effects of catecholamines on resting cortical activity and mechanisms of increased attention . The results differ substantially , however , from findings of increased CBF and metabolism in animals . Although the larger doses used in animals most likely explain the discrepancy , technical limitations in human brain imaging can not be excluded Reduced cerebral perfusion may contribute to the development of cerebrovascular and neurodegenerative diseases . Little is known on cerebral perfusion in the general population , as most measurement techniques are too invasive for application in large groups of healthy individuals . Total cerebral blood flow ( tCBF ) can be noninvasively measured by magnetic resonance imaging ( MRI ) but is highly correlated with brain volume . We calculated total brain perfusion by dividing tCBF by brain volume , and we investigated determinants of total brain perfusion in comparison with tCBF . Secondly , we studied whether persons with a low tCBF or low total brain perfusion have a larger volume of white matter lesions ( WML ) . This study is based on 892 persons aged 60 to 91 years from the Rotterdam Study , a population -based cohort study . We performed two-dimensional ( 2D ) phase-contrast MRI for tCBF measurement . Brain volume and WML volume were quantitatively assessed . Cardiovascular determinants were assessed by interview and physical examination . We assessed associations between cardiovascular determinants and flow measures with linear regression models , adjusted for age and sex . Associations between tCBF or total brain perfusion and WML volume were assessed using general linear models . We found that determinants of tCBF and total brain perfusion differed largely due to the large influence of brain volume on tCBF values . Persons with low total brain perfusion had a significantly larger WML volume compared with those with high total brain perfusion . Prospect i ve studies are required to unravel whether hypoperfusion contributes to WML formation or that tissue damage , manifested by WML , leads to brain hypoperfusion Regional cerebral blood flow ( rCBF ) was studied in 60 elderly persons ( aged 65 to 84 years ) recruited from a population -based study , with single photon emission computed tomography using technetium 99m-labeled hexamethylpropylene amine oxime . We investigated whether it is only age that affects rCBF or whether other factors can be indentified that explain this relationship . Using multiple linear regression analysis , increasing age was significantly associated with rCBF decrease in parietal , temporo-parietal , and temporal cortex , but not in frontal cortex . Adjustment with several risk factors for cerebrovascular disease , including hypertension , history of myocardial infa rct ion , factor VIIc , factor VIIIc , cholesterol and HDL cholesterol , smoking , and diabetes mellitus had no influence on these relations . Conversely , the association between age and rCBF was no longer statistically significant after adjustment with fibrinogen and indicators of carotid atherosclerosis , including intima-media wall thickness of the carotid artery and plaques in the carotid artery . Correction with local ratings of cortical atrophy did not affect the relations between age and rCBF . The results suggest that in the elderly population rCBF declines with age in posterior cortical areas and that these changes may well be explained by the presence of atherosclerosis . Reduced contractility of the vascular muscle wall with increasing age result ing from atherosclerosis may be the underlying mechanism Objectives : To explore relationships between scuba diving activity , brain , and behaviour , and more specifically between global cerebral blood flow ( CBF ) or cognitive performance and total , annual , or last 6 months ’ frequencies , for st and ard dives or dives performed below 40 m , in cold water or warm sea geographical environments . Methods : A prospect i ve cohort study was used to examine divers from diving clubs around Lac Léman and Geneva University Hospital . The subjects were 215 healthy recreational divers ( diving with self-contained underwater breathing apparatus ) . Main outcome measures were : measurement of global CBF by 133Xe SPECT ( single photon emission computed tomography ) ; psychometric and neuropsychological tests to assess perceptual-motor abilities , spatial discrimination , attentional re sources , executive functioning , and memory ; evaluation of scuba diving activity by question naire focusing on number and maximum depth of dives and geographical site of the diving activity ( cold water v warm water ) ; and body composition analyses ( BMI ) . Results : ( 1 ) A negative influence of depth of dives on CBF and its combined effect with BMI and age was found . ( 2 ) A specific diving environment ( more than 80 % of dives in lakes ) had a negative effect on CBF . ( 3 ) Depth and number of dives had a negative influence on cognitive performance ( speed , flexibility and inhibition processing in attentional tasks ) . ( 4 ) A negative effect of a specific diving environment on cognitive performance ( flexibility and inhibition components ) was found . Conclusions : Scuba diving may have long-term negative neurofunctional effects when performed in extreme conditions , namely cold water , with more than 100 dives per year , and maximal depth below 40 Mobile phone use has increased worldwide but its possible effects on the brain remain unclear . The aim of the present study was to investigate the effect of acute exposure to a radio frequency electromagnetic field ( RF EMF ) generated by a mobile phone operating in the Global System for Mobile Communication ( GSM ) 900 MHz on cerebral blood flow . Twenty-nine volunteers attended two experimental sessions : a sham exposure session and a real exposure session in a cross-over double-blind study in which a mobile phone was positioned on the left side of the head . In one session , the mobile phone was operated without RF radiation ( sham phone ) and in the other study it was operated with RF radiation ( real phone ) for 20 min . Thus , each subject served as its own control . Middle cerebral artery blood flow was monitored noninvasively by transcranial Doppler sonography to measure middle cerebral artery blood flow velocity . Pulsatility index and resistance index were also evaluated . A voluntary breath holding physiological test was carried out as a positive control for testing cerebral vasoreactivity . Hemodynamic variables were recorded and analyzed before , during and after mobile phone exposure . No significant changes were detected in studied variables in middle cerebral arteries during sham or real exposure . In the exposed side the cerebral blood flow velocity , the pulsatility index and the resistance index during sham and real exposure were respectively : [ 61.9 ± 1.3 , 61.7 ± 1.3 cm/s ( P = 0.89 ) ] ; [ 0.93 ± 0.03 , 0.90 ± 0.02 ( P = 0.84 ) ] and [ 0.58 ± 0.01 , 0.58 ± 0.01 ( P = 0.96 ) ] at baseline ; and [ 60.6 ± 1.3 , 62 ± 1.6 cm/s ( P = 0.40 ) ] ; [ 0.91 ± 0.03 , 0.87 ± 0.03 ( P = 0.97 ) ] ; [ 0.57 ± 0.01 , 0.56 ± 0.01 ( P = 0.82 ) ] after 20 min of exposure . Twenty minutes of RF exposure to a mobile phone does not seem to affect the cerebral circulation Psychedelic drugs have a long history of use in healing ceremonies , but despite renewed interest in their therapeutic potential , we continue to know very little about how they work in the brain . Here we used psilocybin , a classic psychedelic found in magic mushrooms , and a task-free functional MRI ( fMRI ) protocol design ed to capture the transition from normal waking consciousness to the psychedelic state . Arterial spin labeling perfusion and blood-oxygen level-dependent ( BOLD ) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin . Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD . As predicted , profound changes in consciousness were observed after psilocybin , but surprisingly , only decreases in cerebral blood flow and BOLD signal were seen , and these were maximal in hub regions , such as the thalamus and anterior and posterior cingulate cortex ( ACC and PCC ) . Decreased activity in the ACC/medial prefrontal cortex ( mPFC ) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects . Based on these results , a seed-based pharmaco-physiological interaction/functional connectivity Output:	Several factors ( e.g. , caffeine , aging , and blood gases ) were found to induce a considerable effect on brain perfusion that was consistent across different studies ; for other factors , the modifying effect was found to be debatable , due to contradictory results or lack of evidence .
MS21664	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND VEGFR-2 has a role in gastric cancer pathogenesis and progression . We assessed whether ramucirumab , a monoclonal antibody VEGFR-2 antagonist , in combination with paclitaxel would increase overall survival in patients previously treated for advanced gastric cancer compared with placebo plus paclitaxel . METHODS This r and omised , placebo-controlled , double-blind , phase 3 trial was done at 170 centres in 27 countries in North and South America , Europe , Asia , and Australia . Patients aged 18 years or older with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression on or within 4 months after first-line chemotherapy ( platinum plus fluoropyrimidine with or without an anthracycline ) were r and omly assigned with a central ised interactive voice or web-response system in a 1:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15 , plus paclitaxel 80 mg/m(2 ) intravenously on days 1 , 8 , and 15 of a 28-day cycle . A permuted block r and omisation , stratified by geographic region , time to progression on first-line therapy , and disease measurability , was used . The primary endpoint was overall survival . Efficacy analysis was by intention to treat , and safety analysis included all patients who received at least one treatment with study drug . This trial is registered with Clinical Trials.gov , number NCT01170663 , and has been completed ; patients who are still receiving treatment are in the extension phase . FINDINGS Between Dec 23 , 2010 , and Sept 23 , 2012 , 665 patients were r and omly assigned to treatment-330 to ramucirumab plus paclitaxel and 335 to placebo plus paclitaxel . Overall survival was significantly longer in the ramucirumab plus paclitaxel group than in the placebo plus paclitaxel group ( median 9·6 months [ 95 % CI 8·5 - 10·8 ] vs 7·4 months [ 95 % CI 6·3 - 8·4 ] , hazard ratio 0·807 [ 95 % CI 0·678 - 0·962 ] ; p=0·017 ) . Grade 3 or higher adverse events that occurred in more than 5 % of patients in the ramucirumab plus paclitaxel group versus placebo plus paclitaxel included neutropenia ( 133 [ 41 % ] of 327 vs 62 [ 19 % ] of 329 ) , leucopenia ( 57 [ 17 % ] vs 22 [ 7 % ] ) , hypertension ( 46 [ 14 % ] vs eight [ 2 % ] ) , fatigue ( 39 [ 12 % ] vs 18 [ 5 % ] ) , anaemia ( 30 [ 9 % ] vs 34 [ 10 % ] ) , and abdominal pain ( 20 [ 6 % ] vs 11 [ 3 % ] ) . The incidence of grade 3 or higher febrile neutropenia was low in both groups ( ten [ 3 % ] vs eight [ 2 % ] ) . INTERPRETATION The combination of ramucirumab with paclitaxel significantly increases overall survival compared with placebo plus paclitaxel , and could be regarded as a new st and ard second-line treatment for patients with advanced gastric cancer . FUNDING Eli Lilly and Company BACKGROUND Expression of PD-L1 has been shown to be upregulated in some patients with gastric cancer . As part of the phase 1b KEYNOTE-012 study , we aim ed to assess the safety and activity of the anti-PD-1 antibody pembrolizumab in patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction . METHODS This study was a multicentre , open-label , phase 1b trial done at 13 cancer research centres in the USA , Israel , Japan , South Korea , and Taiwan . We enrolled patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction . Patients received intravenous pembrolizumab at 10 mg/kg once every 2 weeks for 24 months or until progression or unacceptable toxic effects occurred . Response was assessed every 8 weeks in accordance with Response Evaluation Criteria in Solid Tumors version 1.1 . The primary objectives were safety in patients who received at least one dose of pembrolizumab and the proportion of patients achieving overall responses in patients who received at least one pembrolizumab dose and who either had a post-baseline scan or who discontinued therapy because of clinical disease progression or a treatment-related adverse event before the first post-baseline scan . The study is registered with Clinical Trials.gov , number NCT01848834 , and is ongoing but no longer enrolling patients . FINDINGS From Oct 23 , 2013 , to May 5 , 2014 , 39 patients were enrolled . 36 were evaluable for response by central assessment . Eight ( 22 % , 95 % CI 10 - 39 ) patients were judged to have had an overall response at central review ; all responses were partial . All 39 patients were included in the safety analyses . Five ( 13 % ) patients had a total of six grade 3 or 4 treatment-related adverse events , consisting of two cases of grade 3 fatigue , one case each of grade 3 pemphigoid , grade 3 hypothyroidism , and grade 3 peripheral sensory neuropathy , and one case of grade 4 pneumonitis . No treatment-related deaths occurred . INTERPRETATION In this population of patients with recurrent or metastatic PD-L1-positive gastric cancer , pembrolizumab had a manageable toxicity profile and promising antitumour activity , warranting further study in phase 2 and 3 trials . FUNDING Merck & BACKGROUND Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche BACKGROUND Second-line chemotherapy for patients with oesophagogastric adenocarcinoma refractory to platinum and fluoropyrimidines has not shown benefits in health-related quality of life ( HRQoL ) . We assessed whether the addition of docetaxel to active symptom control alone can improve survival and HRQoL for patients . METHODS For this open-labelled , multicentre trial , we recruited patients aged 18 years or older from 30 UK centres . Patients were eligible if they had an advanced , histologically confirmed adenocarcinoma of the oesophagus , oesophagogastric junction , or stomach that had progressed on or within 6 months of treatment with a platinum-fluoropyrimidine combination . Patients could have an Eastern Cooperative Oncology Group performance status of 0 - 2 . We r and omly assigned patients using a central , computerised minimisation procedure to receive docetaxel plus active symptom control , or active symptom control alone ( 1:1 ; stratified by disease status , disease site , duration of response to previous chemotherapy , and performance status ) . Docetaxel was given at a dose of 75 mg/m(2 ) by intravenous infusion every 3 weeks for up to six cycles . The primary endpoint was overall survival , analysed by intention to treat . This is the report of the planned final analysis . This study is an International St and ardised R and omised Controlled Trial , number IS RCT N13366390 . FINDINGS Between April 21 , 2008 , and April 26 , 2012 , we recruited 168 patients , allocating 84 to each treatment group . After a median follow-up of 12 months [ IQR 10 - 21 ] ) and 161 ( 96 % ) deaths ( 80 in the docetaxel group , 81 in the active symptom control group ) , median overall survival in the docetaxel group was 5.2 months ( 95 % CI 4.1 - 5.9 ) versus 3.6 months ( 3.3 - 4.4 ) in the active symptom control group ( hazard ratio 0.67 , 95 % CI 0.49 - 0.92 ; p=0.01 ) . Docetaxel was associated with higher incidence of grade 3 - 4 neutropenia ( 12 [ 15 % ] patients vs no patients ) , infection ( 15 [ 19 % ] patients vs two [ 3 % ] patients ) , and febrile neutropenia ( six [ 7 % ] patients vs no patients ) . Patients receiving docetaxel reported less pain ( p=0.0008 ) and less nausea and vomiting ( p=0.02 ) and constipation ( p=0.02 ) . Global HRQoL was similar between the groups ( p=0.53 ) . Disease specific HRQoL measures also showed benefits for docetaxel in reducing dysphagia ( p=0.02 ) and abdominal pain ( p=0.01 ) . INTERPRETATION Our findings suggest that docetaxel can be recommended as an appropriate second-line treatment for patients with oesophagogastric adenocarcinoma that is refractory to treatment with platinum and fluoropyrimidine . FUNDING Cancer Research UK BACKGROUND The value of second-line therapy for metastatic gastric cancer is unclear . So far there are no r and omised phase III data comparing second-line chemotherapy to best supportive care ( BSC ) . In this prospect i ve , multicenter , open label , r and omised phase III study we compared irinotecan to BSC to evaluate the impact on survival of second-line chemotherapy . METHODS Eligible patients ( pts ) had metastatic or locally advanced gastro-oesophageal junction or gastric adenocarcinoma , objective tumour progression during or within 6months after first-line chemotherapy and ECOG performance status 0 - 2 . Stratification for time of progression after first-line therapy , ECOG PS and pretreatment secured even distribution of important prognostic factors . TREATMENT Arm A : Irinotecan 250mg/m(2)q3w ( first cycle ) to be increased to 350mg/m(2 ) , depending on toxicity . Arm B : BSC . FINDING Output:	PD-1/PD-L1 inhibitors appear to improve the antitumor activity in advanced gastric or gastroesophageal junction cancer patients . However , single-agent PD-1/PD-L1 inhibitor did not result in a relative improvement in OS and PFS compared with chemotherapy in the treatment of patients with advanced gastric or gastroesophageal junction cancer .
MS21665	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Recent prospect i ve data suggest that intake of rapidly digested and absorbed carbohydrates with a high dietary glycemic load is associated with an increased risk of ischemic heart disease . OBJECTIVE We examined whether a high dietary glycemic load was associated with elevated hs-CRP concentrations and whether this association was modified by body mass index ( BMI ; in kg/m(2 ) ) . DESIGN In 244 apparently healthy women , we measured plasma hs-CRP concentrations and determined average dietary glycemic loads with a vali date d semiquantitative food-frequency question naire . Using multiple regression models , we evaluated the association between dietary glycemic load and plasma hs-CRP after adjusting for age ; treatment status ; smoking status ; BMI ; physical activity level ; parental history of myocardial infa rct ion ; history of hypertension , diabetes , and high cholesterol ; postmenopausal hormone use ; alcohol intake ; and other dietary variables . RESULTS We found a strong and statistically significant positive association between dietary glycemic load and plasma hs-CRP . The median hs-CRP concentration for the lowest quintile of dietary glycemic load was 1.9 mg/L and for the highest quintile was 3.7 mg/L ; corresponding multivariate-adjusted geometric means were 1.4 and 3.8 mg/L , respectively ( P for trend < 0.01 ) . This association was significantly modified by BMI . Among women with a BMI greater-than-or-equal 25 , the multivariate-adjusted geometric mean hs-CRP concentration in the lowest quintile was 1.6 mg/L and in the highest quintile was 5.0 mg/L ; however , among women with a BMI < 25 , the corresponding means were 1.1 and 3.1 mg/L , respectively ( P = 0.01 for interaction ) . CONCLUSIONS Dietary glycemic load is significantly and positively associated with plasma hs-CRP in healthy middle-aged women , independent of conventional risk factors for ischemic heart disease . Exacerbation of the proinflammatory process may be a mechanism whereby a high intake of rapidly digested and absorbed carbohydrates increases the risk of ischemic heart disease , especially in overweight women prone to insulin resistance Background Pregnancy and childbirth are associated with weight gain in women , and retention of weight gained during pregnancy can lead to obesity in later life . Diet and physical activity are factors that can influence the loss of retained pregnancy weight after birth . Exercise guidelines exist for pregnancy , but recommendations for exercise after childbirth are virtually nonexistent . The aim of this study was to evaluate the effect of physical activity intervention based on pedometer on physical activity level and anthropometric measures of women after childbirth . Methods We conducted a r and omized controlled trial in which 66 women who had given birth 6 weeks to 6 months prior were r and omly assigned to receive either a 12 week tailored program encouraging increased walking using a pedometer ( intervention group , n = 32 ) or routine postpartum care ( control group , n = 34 ) . During the 12-week study period , each woman in the intervention group wore a pedometer and recorded her daily step count . The women were advised to increase their steps by 500 per week until they achieved the first target of 5000 steps per day and then continued to increase it to minimum of 10,000 steps per day by the end of 12th week . Assessed outcomes included anthropometric measures , physical activity level , and energy expenditure per week . Data were analyzed using the paired t-test , independent t-test , Mann-Whitney , chi-square , Wilcoxon , covariance analysis , and the general linear model repeated measures procedure as appropriate . Results After 12 weeks , women in the intervention group had significantly increased their physical activity and energy expenditure per week ( 4394 vs. 1651 calorie , p < 0.001 ) . Significant differences between-group in weight ( P = 0.001 ) , Body Mass Index ( P = 0.001 ) , waist circumference ( P = 0.001 ) , hip circumference ( P = 0.032 ) and waist-hip ratio ( P = 0.02 ) were presented after the intervention . The intervention group significantly increased their mean daily step count over the study period ( from 3249 before , to 9960 after the intervention , p < 0.001 ) . Conclusion A physical activity intervention based on pedometer is an effective means to increase physical activity ; reducing retention of weight gained during pregnancy and can improve anthropometric measures in postpartum women . Trial registration IS RCT N : I RCT OBJECTIVE : Since post-pregnancy weight retention may contribute to the development of obesity , we sought to determine whether a behavioral weight loss intervention was effective in returning women to their pre-pregnancy weight . METHOD : Ninety women who had given birth in the past 3–12 months and whose weight exceeded their pre-pregnancy weight by at least 6.8 kg were r and omly assigned to either : a ) a six-month behavioral weight loss intervention , delivered via correspondence or b ) a no-treatment control group . Assessment s of body weight , physical activity and eating patterns were conducted at pre-treatment and six months ( post-treatment ) . RESULTS : During the six month treatment , subjects in the correspondence condition lost significantly more weight than control subjects ( 7.8 kg vs 4.9 kg , P=0.03 ) and lost a greater percentage of their excess postpartum weight ( 79 % vs 44 % , P=0.01 ) . Furthermore , a significantly greater percentage of correspondence subjects than controls returned to their pre-pregnancy weight ( 33 % vs 11.5 % , P<0.05 ) . Weight loss in the correspondence group was correlated with completion of self-monitoring records ( r=0.50 , P<0.005 ) . CONCLUSIONS : A behavioral weight loss intervention , delivered via correspondence , appears to be effective in reducing women ’s postpartum weight retention . Future studies should examine the acceptability and the long-term impact of a correspondence postpartum weight loss intervention BACKGROUND & AIMS To establish whether probiotic supplemented dietary counselling influences maternal anthropometric measurements during and after pregnancy . METHODS At the first trimester of pregnancy 256 women were r and omly assigned to receive nutrition counselling to modify dietary intake according to current recommendations or as controls ; dietary intervention groups were further r and omized to receive probiotics Lactobacillus rhamnosus GG ( ATCC 53103 ) and Bifidobacterium lactis ( diet/probiotics ) or placebo ( diet/placebo ) capsules in a double-blind manner , whilst the controls received placebo ( control/placebo ) . The intervention lasted until the end of exclusive breastfeeding for up to six months . RESULTS The risk of central adiposity defined as waist circumference 80 cm or more was lowered in women in the diet/probiotics group compared with the control/placebo group ( OR 0.30 , 95%CI 0.11 - 0.85 , p = 0.023 adjusted for baseline BMI ) , whilst the diet/placebo group did not differ from the controls ( OR 1.00 , 95 % CI 0.38 - 2.68 , p = 0.994 ) at 6 months postpartum . The number needed to treat ( NNT ) with diet/probiotics to prevent one woman from developing a waist circumference of 80 cm or more was 4 . Healthy eating pattern at 12 months postpartum ( p = 0.001 ) and BMI prior to pregnancy ( p < 0.001 ) were strong determinants of BMI at 12 months postpartum when adjusted for dietary intervention and exercise . CONCLUSION The impact of probiotics-supplemented dietary counselling on central adiposity , may offer a novel means for the prevention and management of obesity . This trial was registered at clinical trials.gov as NCT 00167700 , section 3 Background / Objectives : Pregnancy is a life stage where excess weight gain may occur and the postpartum period is often characterised by weight retention . The aim of the current study was to evaluate the feasibility of undertaking a r and omised controlled trial of a weight loss intervention ( WeighWell ) in postpartum women living in areas of social disadvantage . Subjects/ Methods : The study aim ed to recruit 60 women who were not pregnant , 6–18 months postpartum with a body mass index > 25 kg/m2 living in areas of deprivation within Tayside , UK . Recruitment strategies focused on visits to community groups ; writing directly to postpartum women living in areas of deprivation and primary care teams who covered the most deprived 15 % of the population and advertising in community setting s. The 12-week intervention used motivational interviewing techniques to promote an energy deficit diet and increased physical activity , delivered by three face-to-face consultations plus three structured telephone calls . Results : Of 142 women screened , 63 were eligible and 52 ( 83 % ) were recruited and r and omised to an intervention ( n=29 ) or comparison group ( n=23 ) . Over the 12-week intervention , body weight changed significantly by −1.6±2.0 kg in the intervention group compared with + 0.2±2.2 kg in the comparison group , indicating the potential efficacy of the intervention . Loss to follow-up was 24 % in the intervention group and 39 % for the comparison group . Conclusions : The findings support the development of a definitive trial that embraces personalised recruitment strategies and the development of approaches to improve retention over a clinical ly relevant intervention period BACKGROUND The potential risks and benefits of regular exercise during lactation have not been adequately evaluated . We investigated whether regular aerobic exercise had any effects on the volume or composition of breast milk . METHODS Six to eight weeks post partum , 33 sedentary women whose infants were being exclusively breast-fed were r and omly assigned to an exercise group ( 18 women ) or a control group ( 15 women ) . The exercise program consisted of supervised aerobic exercise ( at a level of 60 to 70 percent of the heart-rate reserve ) for 45 minutes per day , 5 days per week , for 12 weeks . Energy expenditure , dietary intake , body composition , and the volume and composition of breast milk were assessed at 6 to 8 , 12 to 14 , and 18 to 20 weeks post partum . Maximal oxygen uptake and the plasma prolactin response to nursing were assessed at 6 to 8 and 18 to 20 weeks . RESULTS The women in the exercise group expended about 400 kcal per day during the exercise sessions but compensated for this energy expenditure with a higher energy intake than that recorded by the control women ( mean [ + /- SD ] , intake , 2497 + /- 436 vs. 2168 + /- 328 kcal per day at 18 to 20 weeks ; P < 0.05 ) . Maximal oxygen uptake increased by 25 percent in the exercising women but by only 5 percent in the control women ( P < 0.001 ) . There were no significant differences between the two groups in maternal body weight or fat loss , the volume or composition of the breast milk , the infant weight gain , or maternal prolactin levels during the 12-week study . CONCLUSIONS In this study , aerobic exercise performed four or five times per week beginning six to eight weeks post partum had no adverse effect on lactation and significantly improved the cardiovascular fitness of the mothers BACKGROUND The retention of weight gained during pregnancy may contribute to obesity . Lactation should promote weight loss , but weight loss is highly variable among lactating women . The risks associated with the restriction of energy intake during lactation have not been adequately evaluated . The purpose of this study was to determine whether weight loss by women during lactation affects the growth of their infants . METHODS We r and omly assigned 40 breast-feeding women who were overweight ( defined as a body-mass index [ the weight in kilograms divided by the square of the height in meters ] of 25 to 30 ) at 4 weeks post partum either to restrict their energy intake by 500 kcal per day and to exercise for 45 minutes per day for 4 days per week ( the diet- and -exercise group ) or to maintain their usual dietary intake and not exercise more than once per week for 10 weeks ( the control group ) . We measured the weight and fat mass of the women and the weight and length of the infants before , during , and at the end of the study period . RESULTS The mean ( + /-SD ) energy intake decreased by 544+/-471 kcal per day in the diet- and -exercise group . As compared with the control group , the women in the diet- and -exercise group lost more weight ( 4.8+/-1.7 kg vs. 0.8+/-2.3 kg , P<0.001 ) and fat mass ( 4.0+/-2.0 kg vs. 0.3+/-1.8 kg , P<0.001 ) . The gains in weight and length of the infants whose mothers were in the diet- and -exercise group ( 1925+/-500 g and 7.8+/-2.0 cm , respectively ) were not significantly different from those of the infants whose mothers were in the control group ( 1861+/-576 g and 7.3+/-1.7 cm ) . CONCLUS Output:	Results from exercise only interventions were inconclusive . Evidence for nutrition only interventions was insufficient . There was insufficient evidence for the effect of post-partum interventions on metabolic risk factors and inflammatory biomarkers .
MS21666	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES To compare outcomes in perception of pain and disability for a group of patients suffering with chronic low-back pain ( CLBP ) when managed in a hospital by either a regional pain clinic or a chiropractor . DESIGN The study was a pragmatic , r and omized , controlled trial . SETTING The trial was performed at a National Health Service ( NHS ) hospital outpatient clinic ( pain clinic ) in the United Kingdom . SUBJECTS AND INTERVENTIONS Patients with CLBP ( i.e. , symptom duration of > 12 weeks ) referred to a regional pain clinic ( outpatient hospital clinic ) were assessed and r and omized to either chiropractic or pain-clinic management for a period of 8 weeks . The study was pragmatic , allowing for normal treatment protocol s to be used . Treatment was administered in an NHS hospital setting . OUTCOME MEASURES The Rol and -Morris Disability Question naire ( RMDQ ) and Numerical Rating Scale were used to assess changes in perceived disability and pain . Mean values at weeks 0 , 2 , 4 , 6 , and 8 were calculated . The mean differences between week 0 and week 8 were compared across the two treatment groups using Student 's t-tests . Ninety-five percent ( 95 % ) confidence intervals ( CIs ) for the differences between groups were calculated . RESULTS R and omization placed 12 patients in the pain clinic and 18 in the chiropractic group , of which 11 and 16 , respectively , completed the trial . At 8 weeks , the mean improvement in RMDQ was 5.5 points greater for the chiropractic group ( decrease in disability by 5.9 ) than for the pain-clinic group ( 0.36 ) ( 95 % CI 2.0 points to 9.0 points ; p = 0.004 ) . Reduction in mean pain intensity at week 8 was 1.8 points greater for the chiropractic group than for the pain-clinic group ( p = 0.023 ) . CONCLUSIONS This study suggests that chiropractic management administered in an NHS setting may be effective for reducing levels of disability and perceived pain during the period of treatment for a sub population of patients with CLBP OBJECTIVE For long-term treatment effects , patients with subacute back pain need to adhere to treatment recommendations beyond the prescribed exercise treatment . Adherence rates are as low as 30 % , so we developed a cognitive-behavioural training programme to enhance patients ' self-efficacy , maximise severity perceptions and reduce barrier perceptions . METHOD A 2 x 4 ( group x time ) repeated measurement design was applied . Forty-seven patients with non-specific , subacute back pain were r and omly assigned to a training group ( exercise treatment plus cognitive-behavioural training programme ) or a control group ( exercise treatment only ) . RESULTS Repeated measures ANOVA revealed significant main and interaction effects ; the training group reported enhanced self-efficacy and severity perceptions , reduced barrier perceptions , and self-reported that they exercised more often than the control group over time . However , no group differences regarding pain intensity emerged . CONCLUSION Our findings demonstrate that a short and inexpensive cognitive-behavioural training programme is an effective tool to enable back pain patients to follow treatment recommendations on a regular basis . PRACTICE IMPLICATION S The short and simple intervention can easily be conducted by personnel , other than psychologists , i.e. , physiotherapists OBJECTIVE To test the hypothesis that articles with negative results are more likely than articles with positive results to be published in journals with lower impact factor . DESIGN AND SETTING We selected all of the r and omized , placebo-controlled trials conducted during the neonatal period between October 1 , 1998 , and October 1 , 2003 . Trials were classified as having positive results or negative results ( significant or no significant difference , respectively ) . Only studies dealing with primary outcomes ( efficacy ) were included . MAIN OUTCOME MEASURES The impact factor of each journal was determined , and the sample size for each study was noted . RESULTS There were 233 articles that fulfilled the inclusion criteria . There was a significant difference between the 2 groups in terms of impact factor ( P = .03 ) but not sample size ( P = .30 ) . Impact factor correlated with both sample size and the type of study results ( positive results vs negative results ; P<.05 ) . CONCLUSION Articles with negative results are more likely than articles with positive results to be published in journals with lower impact factor STUDY DESIGN A controlled clinical trial . OBJECTIVES To assess the effects of an integrated back stability ( IBS ) programme on a chronic low back pain ( CLBP ) population in a time restricted private clinic environment . BACKGROUND Studies assessing stability training CLBP have reported inconsistent results . Methods used within trials vary , with some authors focusing on muscle isolation and others using whole body movements . IBS uses an exercise progression beginning with posturally based exercise and progressing from muscle isolation through to complex movements . METHODS AND MEASURES Fifty-nine chronic low back patients were divided into control ( n=32 ) and intervention ( n=27 ) groups . Participants in the intervention group were prescribed a 6 week individualized exercise programme in three stages . In stage 1 , exercises addressed posture and movement dysfunction and activated the core stabilizing muscles . In stage 2 , ' back fitness ' was enhanced using progressive exercise principles . Stage 3 emphasized technique specific actions . Participants in the control group received a backcare advice leaflet only . RESULTS Pre- and post-test scores were analysed for each of the outcome measures within the control group using a Wilcoxin signed ranks test . At an alpha level of p < or=0.0071 , no differences were observed . For the intervention group , a Mann-Whitney U-test showed significant differences between groups in the Rol and and Morris Disability Question aire ( RMDQ ) , short form McGill Pain Question naire ( SF-MPQ ) , and the Tampa Scale of Kinesiophobia ( TSK ) ( p < or=0.0071 ) . Patient satisfaction was assessed by question naire , 89 % of patients considering their level of pain and functional impairment acceptable following the programme . CONCLUSION IBS significantly reduced pain and disability in the subject group studied . Patients reported a positive experience of the programme OBJECTIVE To evaluate the effectiveness of the addition of back school to exercise and physical treatment modalities in relieving pain and improving the functional status of patients with chronic low back pain . DESIGN A r and omized controlled trial . PATIENTS A total of 146 patients with chronic low back pain were enrolled in the study . METHODS Subjects were divided into 2 groups : the back school group received exercise , physical treatment modalities and a back school programme ; and the control group received exercise and physical treatment modalities . Treatment efficacy was evaluated at the end of treatment and 3 months post-treatment , in terms of pain , measured with the Visual Analogue Scale , and functional status , measured with the Oswestry Low Back Pain Disability Question naire . RESULTS In both groups , Visual Analogue Scale and Oswestry Low Back Pain Disability Question naire were significantly reduced after therapy ( p < 0.01 ) , but the difference between the scores at the end of treatment and 3 months post-treatment was not significant . There was a significant improvement in Visual Analogue Scale and Oswestry Low Back Pain Disability Question naire in the back school group compared with the control group at the end of therapy and 3 months post-treatment ( p < 0.05 ) . CONCLUSION The addition of back school was more effective than exercise and physical treatment modalities alone in the treatment of patients with chronic low back pain INTRODUCTION Chronic , nonspecific low back pain is a difficult ailment to treat and poses an economic burden in terms of medical expenses and productivity loss . The aim of this study was to determine the efficacy and safety of intramuscular metylcobalamin in the treatment of chronic nonspecific low back pain . METHODS This was a double-blinded , r and omised , controlled experimental study . 60 patients were assigned to either the methylcobalamin group or the placebo group . The former received intramuscular injections of 500 mcg parenteral methylcobalamin in 1 ml solution three times a week for two weeks , and the placebo group received 1 ml normal saline . Patients were assessed with Oswestry Disability Index question naire Version 2.0 and Visual Analogue Scale pain score . They were scored before commencement of the injections and at two months interval . RESULTS Of the 60 patients , 27 received the placebo injections and 33 were given methylcobalamin injections . A total of 58 patients were available for review at two months ( placebo : n is 26 ; methylcobalamin : n is 32 ) . There was a significant improvement in the Oswestry Disability Index and Visual Analogue Scale pain scores in the methylcobalamin group as compared with the placebo group ( p-value less than 0.05 ) . Only minor adverse reactions such as pain and haematoma at the injection sites were reported by some patients . CONCLUSION Intramuscular methylcobalamin is both an effective and safe method of treatment for patients with nonspecific low back pain , both singly or in combination with other forms of treatment There is limited evidence that preprogrammed feedforward adjustments , which are modified in people with neurological and musculoskeletal conditions , can be trained and whether this depends on the type of training . As previous findings demonstrate consistent delays in feedforward activation of the deep abdominal muscle , transversus abdominis ( TrA ) , in people with recurrent low back pain ( LBP ) , we investigated whether training involving voluntary muscle activation can change feedforward mechanisms , and whether this depends on the manner in which the muscle is trained . Twenty-two volunteers with recurrent LBP were r and omly assigned to undertake either training of isolated voluntary activation of TrA or sit-up training to activate TrA in a non-isolated manner to identical amplitude . Subjects performed a trunk perturbation task involving arm movement prior to and after training , and surface and fine-wire electromyography ( EMG ) recordings were made from trunk and arm muscles . Following a single session of training of isolated voluntary activation of TrA , onset of TrA EMG was earlier during rapid arm flexion and extension , to more closely resemble the responses in pain-free individuals . The magnitude of change in TrA EMG onset was correlated with the quality of isolated training . In contrast , all of the abdominal muscles were recruited earlier during arm flexion after sit-up training , while onset of TrA EMG was further delayed during arm extension . The results provide evidence that training of isolated muscle activation leads to changes in feedforward postural strategies , and the magnitude of the effect is dependent on the type and quality of motor training BACKGROUND To our knowledge , verum acupuncture has never been directly compared with sham acupuncture and guideline -based conventional therapy in patients with chronic low back pain . METHODS A patient- and observer-blinded r and omized controlled trial conducted in Germany involving 340 outpatient practice s , including 1162 patients aged 18 to 86 years ( mean + /- SD age , 50 + /- 15 years ) with a history of chronic low back pain for a mean of 8 years . Patients underwent ten 30-minute sessions , generally 2 sessions per week , of verum acupuncture ( n = 387 ) according to principles of traditional Chinese medicine ; sham acupuncture ( n = 387 ) consisting of superficial needling at nonacupuncture points ; or conventional therapy , a combination of drugs , physical therapy , and exercise ( n = 388 ) . Five additional sessions were offered to patients who had a partial response to treatment ( 10%-50 % reduction in pain intensity ) . Primary outcome was response after 6 months , defined as 33 % improvement or better on 3 pain-related items on the Von Korff Chronic Pain Grade Scale question naire or 12 % improvement or better on the back-specific Hanover Functional Ability Question naire . Patients who were unblinded or had recourse to other than permitted concomitant therapies during follow-up were classified as nonresponders regardless of symptom improvement . RESULTS At 6 months , response rate was 47.6 % in the verum acupuncture group , 44.2 % in the sham acupuncture group , and 27.4 % in the conventional therapy group . Differences among groups were as follows : verum vs sham , 3.4 % ( 95 % confidence interval , -3.7 % to 10.3 % ; P = .39 ) ; verum vs conventional therapy , 20.2 % ( 95 % confidence interval , 13.4 % to 26.7 % ; P < .001 ) ; and sham vs conventional therapy , 16.8 % ( 95 % confidence interval , 10.1 % to 23.4 % ; P < .001 . CONCLUSIONS Low back pain improved after acupuncture treatment for at least 6 months . Effectiveness of acupuncture , either verum or sham , was almost twice that of conventional therapy Background The evidence that exercise intervention is effective for treatment of chronic low back pain comes from trials that are not placebo-controlled . Objective The purpose of this study was to investigate the efficacy of motor control exercise for people with chronic low back pain . Design This was a r and omized , placebo-controlled trial . Setting The study was conducted in an outpatient physical therapy department in Australia . Patients The participants were 154 patients with chronic low back pain of more than 12 weeks ’ duration . Intervention Twelve sessions of motor control exercise ( ie , exercises design ed to improve function of specific muscles of the low back region and the control of posture and movement ) or placebo ( ie , detuned ultrasound therapy and detuned short-wave therapy ) were conducted over 8 weeks . Measurements Primary outcomes were pain intensity , activity ( measured by the Patient Output:	Effect size is not associated with impact factor , reporting of funding source , or reporting of conflicts of interest . Conclusions The absence of associations between effect size and impact factor , reporting sources of funding , and conflicts of interest reflects positively on research and publisher conduct in the field . Strong evidence of a large association between absolute magnitude of effect size and explicit reporting of ‘ no funding ’ suggests authors of unfunded trials are likely to report larger effect sizes , notwithst and ing direction . This could relate in part to quality , re sources , and /or how pragmatic a trial is
MS21667	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: INTRODUCTION The purpose s of the study were to evaluate the immediate damage to roots and periodontal structures after initial miniscrew implant ( MSI ) placement and the short- and long-term damage after MSIs were left in situ . METHODS The roots of the maxillary second , third , and fourth premolars of 7 mature beagle dogs were r and omly assigned to undergo immediate , short-term ( left for 6 weeks ) , or long-term ( left for 12 weeks ) damage . Intentional damage was inflicted with self-tapping screws ( 1.8 x 8 mm ) placed with a stent . Alternating tetracycline and calcein labels were administered at 6-week intervals . Undecalcified sections were stained and evaluated histologically to determine the extent of damage ; healing was evaluated by using fluorescence labels . RESULTS Histology showed damage to 73.8 % of the teeth , ranging from displacement of bone into the periodontal ligament to invasion of the pulp chamber . Displacement of bone into the periodontal ligament and direct damage to the periodontal ligament occurred in 3 ( 7.2 % ) instances . Damage was isolated to the cementum of 8 ( 19.0 % ) teeth , whereas damage occurred in the dentin of 11 ( 26.2 % ) teeth . Loss of bone in the furcation was evident in 3 ( 7.2 % ) teeth , and severe damage into the pulp occurred in 6 ( 14.2 % ) teeth . No differences in the amounts of damage were evident between the immediate , short- , and long-term groups . Healing often occurred with cementum around the unloaded MSIs . CONCLUSIONS Extensive damage can be caused by MSIs , with little to no differences evident over time . Unloaded MSIs that remain in contact with roots of teeth can show varying degrees of healing PURPOSE The aim of this prospect i ve clinical study was to assess the risk factors associated with failure of mini-implants used for orthodontic anchorage . MATERIAL S AND METHODS A total of 140 mini-implants in 44 patients , including 48 miniplates and 92 freest and ing miniscrews , were examined in the study . A variety of orthodontic loads were applied . The majority of implants were placed in the posterior maxilla ( 104/140 ) , and the next most common location was the posterior m and ible ( 34/140 ) . RESULTS A cumulative survival rate of 89 % ( 125/140 ) was found by Kaplan-Meier analysis . There was no significant difference in the survival rate between miniplates and freest and ing miniscrews , but miniplates were used in more hazardous situations . The Cox proportional-hazards regression model identified anatomic location and peri-implant soft tissue character as 2 independent prognostic indicators . The estimated relative risk of implant failure in the posterior m and ible was 1.101 ( 95 % confidence interval , 0.942 to 1.301 ; P = .046 ) . The risk ratio of failure for implants surrounded by nonkeratinized mucosa was 1.117 ( 95 % confidence interval , 0.899 to 1.405 ; P = .026 ) . DISCUSSION AND CONCLUSION The results confirmed the effectiveness of orthodontic mini-implants , but in certain situations adjustment of the treatment plan or modifications in the technique of implant placement may lead to improved success rates INTRODUCTION The purpose of this study was to investigate the effects of the diameter and shape of orthodontic mini-implants ( OMIs ) on microdamage to the cortical bone during implant placement . METHODS Twenty-eight self-drilling OMIs ( Bio material s Korea , Seoul , Korea ; length , 6 mm ; diameters , 1.5 and 2 mm ; cylindrical and tapered shapes ; classified as 1.5C , 2C , 1.5 T , and 2 T ) were placed with a surgical device in the tibias of 7 New Zeal and white rabbits ( mature males ; mean age , 6 months ; mean weight , 3.1 kg ) . Four OMIs of each type per rabbit were placed r and omly . Maximum insertion torque ( MIT ) was measured . Immediately after placement of the OMIs , the block of bone with the OMI was harvested . Cortical bone thickness was measured by using microcomputed tomography , and histomorphometric analyses of the number of cracks ( NC ) , accumulated crack length ( ACL ) , maximum radius of the crack ( MRC ) , and longest crack ( LC ) were performed . Kruskal-Wallis and Mann-Whitney U tests with the Bonferroni adjustment were done for statistical analyses . RESULTS Increased diameter ( 1.5C<2C and 1.5T<2 T ) and tapering ( 1.5C<2 T ) result ed in increased values of MIT , NC , and LC ( P < 0.01 , respectively ) . Similarly , with increased diameters ( 1.5C and 1.5T<2C and 2 T ) , there were increases of ACL and MRC ( P < 0.001 , respectively ) . However , there were no differences in the values of MIT , NC , ACL , MRC , and LC between the cylindrical and tapered OMIs with the same diameters ( 1.5C and 1.5 T , 2C and 2 T ) . CONCLUSIONS OMIs with larger diameters and tapered shapes caused greater microdamage to the cortical bone ; this might affect bone remodeling and the stability of the OMIs PURPOSE This study evaluated the survival parameters of single-tooth implants through clinical and radiographic analysis . MATERIAL S AND METHODS Implants were restored within a 24-hour period with a provisional crown design ed to receive an occlusal masticatory load . This approach was compared to implants restored after a healing period ( the control group ) . Forty-six implants were placed in 23 patients who were each treated with 2 Frialit-2 implants placed in sites between the second premolar in the maxilla or m and ible . The manufacturer 's recommended formal surgical procedure was followed , and primary stability was st and ardized with a minimum insertion torque of 20 Ncm . The sites were r and omly selected , and the clinical and radiographic parameters were st and ardized with individual templates . RESULTS Data were collected at 24 h , and at 1 , 3 , 6 , 12 , 18 , and 24 months . The experimental group included 10 failed implants ; 9 of the failed implants had been placed with an insertion torque of 20 Ncm . One implant from the control group failed during the 24-month follow-up period . The survival rate was independent of implant length , site position , and bone quality and quantity . Relative risk for implant failure was associated with insertion torque ( relative risk 0.79 [ CI : 0.66 - 0.930 ] ; Cox regression ) ( P < or = .007 ) , in the experimental group but was not significant for those in the control group ( ie , implants placed after a healing period ; relative risk 0.78 [ CI : 0.34 - 1.78 ] ; Cox regression ) ( P < or = .057 ) . To achieve osseointegration , it was found that an insertion torque above 32 Ncm was necessary ( chi2= 15.68 ; P < or = .004 ) . DISCUSSION A careful evaluation is necessary for a better underst and ing of the survival rates of immediately loaded implants . In this study , insertion torque was associated with the potential for risk , which can be decreased by 20 % per 9.8 Ncm added . CONCLUSION Given these results , and considering the number of patients treated , immediate provisional crowns should only be proposed with early loading if an appropriate initial insertion torque has been applied INTRODUCTION We compared the stability of 3- and 6-mm long miniscrew implants ( MSIs ) loaded with orthopedic force levels . METHODS Using a split-mouth experimental design , we placed MSIs into the jaws of 5 mature beagle dogs and immediately loaded them for 6 weeks . Continuous forces were applied by reciprocally loading pairs of MSIs with nickel-titanium coil springs . The m and ibles had the 3-mm MSIs r and omly loaded with forces of 600 or 900 g. In the maxilla , the 3- and 6-mm MSIs were r and omly assigned and loaded with 600 g of force . An unloaded , control MSI was placed in each quadrant . Overall success was defined as MSIs that remained intact ; net success rates excluded MSIs that had sheared off and all implants placed in a dog that frequently chewed his run bars and food bowl . RESULTS The overall success rates of the loaded and the control 6-mm MSIs were 100 % . Overall and net success rates for the 3-mm experimental MSIs were 66.7 % and 95.2 % , respectively . Similarly , the overall and net success rates of the 3-mm control MSIs were 66.7 % and 81.8 % , respectively . The overall success rates of the 3-mm m and ibular MSIs loaded with 900 and 600 g of force were both 60 % ; their net success rates were 100 % with 900 g and 85.7 % with 600 g. Overall success rates of the 3-mm experimental MSIs in the maxilla and the m and ible were 80 % and 60 % , repectively . The net success rates were 100 % ( maxilla ) and 85.7 % ( m and ible ) . There were no significant ( P > 0.05 ) differences in stability associated with force or location . The loaded 3- and 6-mm MSI pairs demonstrated significant decreases in interimplant distance , averaging 2.2 and 1.8 mm , respectively ; the 3-mm MSIs loaded with 900 g showed significantly more displacement than those loaded with 600 g. CONCLUSIONS Success rates of immediately loaded 3-mm MSIs were significantly lower than those of immediately loaded 6-mm MSIs . Neither force nor location explained differences in the success rates . The linear displacements of the MSIs were associated with load amount rather than implant length Miniscrews have been used in recent years for anchorage in orthodontic treatment . However , it is not clear whether the miniscrews are absolutely stationary or move when force is applied . Sixteen adult patients with miniscrews ( diameter = 2 mm , length = 17 mm ) as the maxillary anchorage were included in this study . Miniscrews were inserted on the maxillary zygomatic buttress as a direct anchorage for en masse anterior retraction . Nickel-titanium closed-coil springs were placed for the retraction 2 weeks after insertion of the miniscrews . Cephalometric radiographs were taken immediately before force application ( T1 ) and 9 months later ( T2 ) . The cephalometric tracings at T1 and T2 were superimposed for the overall best fit on the structures of the maxilla , cranial base , and cranial vault to determine any movement of the miniscrews . The miniscrews were also evaluated clinical ly for their mobility ( 0 : no movement , 1 : < or = 0.5 mm , 2 : 0.5 - 1.0 mm , 3 : > 1.0 mm ) . The mobility of all miniscrews was 0 at T1 and T2 . On average , the miniscrews tipped forward significantly , by 0.4 mm at the screw head . The miniscrews were extruded and tipped forward ( -1.0 to 1.5 mm ) in 7 of the 16 patients . Miniscrews are a stable anchorage but do not remain absolutely stationary throughout orthodontic loading . They might move according to the orthodontic loading in some patients . To prevent miniscrews hitting any vital organs because of displacement , it is recommended that they be placed in a non-tooth-bearing area that has no foramen , major nerves , or blood vessel pathways , or in a tooth-bearing area allowing 2 mm of safety clearance between the miniscrew and dental root The possibility of using osseointegrated implants for orthodontic anchorage is well known . When absolute orthodontic anchorage is needed , mini-implants can be inserted in the non-alveolar bone area ( e.g. palatal process or retromolar areas of the m and ible ) . However , what happens to these implants at the end of treatment can be a problem as neither trephine explantation nor simply leaving the subgingival part of the implant in the bone permanently are acceptable solutions . In this investigation , 16 Exacta small screw titanium implants ( Exacta MS series conical profile , with a diameter of 3.3 mm and a length of 7.0 mm ) were used as indirect orthodontic anchorage in 16 adult patients . The site of implant placement was established based on radiological investigations . There were eight palatal and eight retromolar implants inserted in seven males and nine females ( mean age 30.3 years ) . On completion of treatment , the implants were unscrewed to the maximum limits of their removal torque values ( RTVs ) and the obtained data were analysed using a t-test . An in vitro study before the clinical trial was also undertaken to determine the maximum mechanical resistance of the unscrewing system . The clinical procedure and average RTV ( 67.91 + /- 12.47 N/cm ) were considered compatible with safe , non-invasive removal of the implant followed by rapid anatomical reconstruction of the area involved OBJECTIVE To test the hypothesis that there is no difference in the stability and resistance to rotational moments of early loaded s and blasted and acid-etched ( SLA ) mini-implants and those of machined-surface implants of the same size and shape . MATERIAL S AND METHODS A r and omized complete block design was used in 12 skeletally mature Output:	Currently , no evidence indicates that specific maximum insertion torque levels are associated with higher success rates for orthodontic mini-implants .
MS21668	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Cognitive performance includes the processes of attention , memory , processing speed , and executive functioning , which typically declines with aging . Previous research has demonstrated that aerobic and resistance exercise improves cognitive performance immediately following exercise . However , there is limited research examining the effect that a cognitively complex exercise such as martial art training has on these cognitive processes . Our study compared the acute effects of 2 types of martial art training to aerobic exercise on cognitive performance in middle-aged adults . We utilized a repeated measures design with the order of the 3 exercise conditions r and omly assigned and counterbalanced . Ten recreational middle-aged martial artists ( mean age = 53.5 ± 8.6 years ) participated in 3 treatment conditions : a typical martial art class , an atypical martial art class , and a one-hour walk at a self-selected speed . Cognitive performance was assessed by the Stroop Color and Word test . While all 3 exercise conditions improved attention and processing speed , only the 2 martial art conditions improved the highest order of cognitive performance , executive function . The effect of the 2 martial art conditions on executive function was not different . The improvement in executive function may be due to the increased cortical dem and required by the more complex , coordinated motor tasks of martial art exercise compared to the more repetitive actions of walking Injuries can be an adverse outcome of participation in sport and recreational activities . The aim of this study was to determine the public health impact of injury during sports and active recreation injury in a select population in Australia . A r and om household telephone survey was conducted quarterly over a 12-month period in a well-defined geographic region , the Latrobe Valley , Australia . Information was collected on participation in sport and active recreation and associated injuries over the previous 2 weeks for all household members aged over 4 years . Injury rates were calculated per 10,000 population and per 1000 sports participants . Data were collected on 1084 persons from 417 households . Overall , 648 people reported participating in at least one sport or active recreation and 34 ( 5.2 % , 95 % CI : 4.8 , 5.6 % ) of these sustained an injury during this activity . Overall , 51.4 % of injured cases had a significant impact : 26.5 % sought treatment , 34.4 % had their activities of daily living adversely affected and 36.0 % had their performance/participation limited . Cricket ( 51 injuries/10,000 population ) , horse riding ( 29/10,000 population ) and basketball ( 25/10,000 population ) had the highest injury rates . After adjusting for participation , cricket ( 242 injuries/1000 participants ) , horse riding ( 122/1000 participants ) and soccer ( 107/1000 participants ) had the highest injury rates . Cricket and soccer were the sports most associated with ' significant ' injuries . Injury prevention efforts should be aim ed at team ball sports ( especially cricket , soccer and netball ) because of their comparatively high rate of both overall and ' significant ' injury [ Purpose ] The aim of this study was to investigate the effects of Ving Tsun ( VT ) Chinese martial art training on radial bone strength , upper- and lower-limb muscular strength , shoulder joint mobility , balance performance , and self-efficacy in elderly participants . [ Subjects and Methods ] Twelve seniors voluntarily joined the VT training group , and twenty-seven seniors voluntarily joined the control group . The VT group received VT training for three months , while the control group received no training . The bone strength of the distal radius was assessed using an ultrasound bone sonometer . Muscular strength in the limbs was evaluated using a Jamar h and grip dynamometer and the five times sit-to-st and test . Shoulder joint mobility was examined using a goniometer . Balance performance and self-efficacy were evaluated using the Berg Balance Scale and the Chinese version of the Activities-specific Balance Confidence Scale , respectively . [ Results ] The results revealed a nonsignificant group-by-time interaction effect , group effect , and time effect for all outcome variables . However , general trends of maintenance or improvement in all outcome parameters were observed to a greater extent in the VT group than in the control group . [ Conclusion ] VT training might be a potential fall-prevention exercise that can be used to maintain general physique , balance , and confidence in the elderly population . A further r and omized controlled trial is needed to confirm this postulation AIM the purpose of this study was to examine the effect of kickboxing training on physical fitness . METHODS 30 subjects were r and omized into a kickboxing-group ( n=15 ) and control group ( n=15 ) . Each group trained approximately 1-hour per day , three-times per a week during five weeks . Muscle-power ( upper-body : bench-press-test , medicine-ball-test ; lower-body : squat-jump and counter-movement-jump-test ) , flexibility , speed and agility , aerobic ( progressive maximal exercise test ) , anaerobic fitness ( Wingate test ) and body composition were assessed before and after the training period . RESULTS the kickboxing group showed significant improvement ( p < 0.05 ) in upper-body muscle power , aerobic power , anaerobic fitness , flexibility , speed and agility after training whereas body composition , squat jump and counter movement jump ( height , power and velocity components ) did not change for both groups . CONCLUSION kickboxing- practice was effective to change many physical variables . Thus , this activity can be useful for enhancing physical fitness , but complementary activities and /or nutritional interventions should be necessary Objective : To investigate the epidemiology of sports and recreation-related injury ( SRI ) among emergency department ( ED ) attendees . Design : Descriptive epidemiology study . Setting : An Irish university hospital ED . Participants : All patients aged over 4 years attending a large regional ED , during a 6-month period , for the treatment of SRI were prospect ively surveyed . Assessment of Risk Factors : In all cases identified as SRI the attending physician completed a specifically design ed question naire . It was postulated that recreation-related injury is a significant proportion of reported SRI . Results : Fracture rate was highest in the 4–9-year age group ( 44 % ) . On multivariate logistic regression the adjusted odds ratio ( OR ; 95 % CI ) of fracture was higher for children ( vs adults ) at 1.21 ( 1.0 to 1.45 ) . The adjusted OR was higher for upper-limb 5.8 ( 4.5 to 7.6 ) and lower-limb injuries 1.87 ( 1.4 to 2.5 ) versus axial site of injury and for falls 2.2 ( 1.6 to 2.9 ) and external force 1.59 ( 1.2 to 2.1 ) versus an overextension mechanism of injury . In the same model , “ play ” was independently associated with fracture risk , adjusted OR 1.98 ( 1.2 to 3.0 ; p = 0.001 ) versus low-risk ball sports 1.0 ( reference ) ; an effect size similar to that seen for combat sports 1.96 ( 1.2 to 3.3 ; p = 0.01 ) and greater than that seen for presumed high-risk field sports 1.4 ( 0.9 to 2.0 ) Conclusion : Fall and subsequent upper-limb injury was the commonest mechanism underlying SRI fracture . Domestic “ play ” in all age groups at the time of injury accorded a higher fracture risk than field sports . Patient education regarding the dangers of unsupervised play and recreation represents a means of reducing the burden of SRI IMPORTANCE Few studies have examined how different proportions of moderate and vigorous physical activity affect health outcomes . OBJECTIVE To examine whether the proportion of total moderate to vigorous activity ( MVPA ) that is achieved through vigorous activity is associated with all-cause mortality independently of the total amount of MVPA . DESIGN , SETTING , AND PARTICIPANTS We performed a prospect i ve cohort study with activity data linked to all-cause mortality data from February 1 , 2006 , through June 15 , 2014 , in 204,542 adults aged 45 through 75 years from the 45 and Up population -based cohort study from New South Wales , Australia ( mean [ SD ] follow-up , 6.52 [ 1.23 ] years ) . Associations between different contributions of vigorous activity to total MVPA and mortality were examined using Cox proportional hazards models , adjusted for total MVPA and sociodemographic and health covariates . EXPOSURES Different proportions of total MVPA as vigorous activity . Physical activity was measured with the Active Australia Survey . MAIN OUTCOMES AND MEASURES All-cause mortality during the follow-up period . RESULTS During 1,444,927 person-years of follow-up , 7435 deaths were registered . Compared with those who reported no MVPA ( crude death rate , 8.34 % ) , the adjusted hazard ratios for all-cause mortality were 0.66 ( 95 % CI , 0.61 - 0.71 ; crude death rate , 4.81 % ) , 0.53 ( 95 % CI , 0.48 - 0.57 ; crude death rate , 3.17 % ) , and 0.46 ( 95 % CI , 0.43 - 0.49 ; crude death rate , 2.64 % ) for reporting 10 through 149 , 150 through 299 , and 300 min/wk or more of activity , respectively . Among those who reported any MVPA , the proportion of vigorous activity revealed an inverse dose-response relationship with all-cause mortality : compared with those reporting no vigorous activity ( crude death rate , 3.84 % ) the fully adjusted hazard ratio was 0.91 ( 95 % CI , 0.84 - 0.98 ; crude death rate , 2.35 % ) in those who reported some vigorous activity ( but < 30 % of total activity ) and 0.87 ( 95 % CI , 0.81 - 0.93 ; crude death rate , 2.08 % ) among those who reported 30 % or more of activity as vigorous . These associations were consistent in men and women , across categories of body mass index and volume of MVPA , and in those with and without existing cardiovascular disease or diabetes mellitus . CONCLUSIONS AND RELEVANCE Among people reporting any activity , there was an inverse dose-response relationship between proportion of vigorous activity and mortality . Our findings suggest that vigorous activities should be endorsed in clinical and public health activity guidelines to maximize the population benefits of physical activity BACKGROUND Given the evidence that regular physical activity produces substantial health benefits , participation in sports , exercise , and recreation is widely encouraged . The objective of this study was to describe participation in sports , exercise , and recreational physical activities among US adults . METHODS Data from 2 national surveys of respondents age 18 years and older were analyzed . Respondents to the American Time Use Survey ( ATUS ) from 2003 through 2005 ( N=45,246 ) reported all activities on 1 r and omly selected survey day . Respondents to the National Health and Nutrition Examination Survey ( NHANES ) from 1999 through 2004 ( N=17,061 ) reported leisure-time physical activities in the 30 days before the interview . RESULTS One-quarter of adults participated in any sport , exercise , or recreational activity on a r and om day , and 60.9 % of adults participated in any leisure-time activity in the previous 30 days . The most common types of activities were walking , gardening and yard work , and other forms of exercise . The sports and recreational activities had typical duration s of 1/2 to 3 hours per session , and the exercise activities typically lasted 1 hour or less . CONCLUSIONS The prevalence of sports , exercise , and recreational physical activities is generally low among US adults ; exercise is the most commonly reported type of activity BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application Self-reported rates of participation in sport vary by country . In the UK , about 40 % of men and women aged 16 years or older participate in at least one sport every week . Although few data exist to assess trends for participation in sport , there is little evidence of change in the past de Output:	The majority of studies reported positive effects result ing from hard martial arts practice , showing some improvement and maintenance of balance , cognitive function and psychological health . Benefits may be obtained regardless of the age of practice commencement . “ Hard ” martial arts seem to have potential to improve balance and cognitive functions that decline with age , which can lead to poorer health outcomes among the elderly ( e.g. cognitive decline , falls and fractures ) .
MS21669	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objectives : Physiotherapy programmes so far mainly address the lateral deformity of scoliosis , a few aim at the correction of rotation and only very few address the sagittal profile . Meanwhile , there is evidence that correction forces applied in the sagittal plane are also able to correct the scoliotic deformity in the coronal and frontal planes . So it should be possible to improve excellence in scoliosis rehabilitation by the implementation of exercises to correct the sagittal deformity in scoliosis patients . An exercise programme ( physio-logic ® exercises ) aim ing at a physiologic sagittal profile was developed to add to the programme applied at the centre or to replace certain exercises or exercising positions . Material and methods : To test the hypothesis that physio-logic ® exercises improve the outcome of Scoliosis Intensive Rehabilitation ( SIR ) , the following study design was chosen : Prospect i ve controlled trial of pairs of patients with idiopathic scoliosis matched by sex , age , Cobb angle and curve pattern . There were 18 patients in the treatment group ( SIR + physio-logic ® exercises ) and 18 patients in the control group ( SIR only ) , all in matched pairs . Average Cobb angle in the treatment group was 34.5 ° ( SD 7.8 ) Cobb angle in the control group was 31.6 ° ( SD 5.8 ) . Age in the treatment group was at average 15.3 years ( SD 1.1 ) and in the control group 14.7 years ( SD 1.3 ) . Thirteen of the 18 patients in either group had a brace . Outcome parameter : average lateral deviation ( mm ) , average surface rotation ( ° ) and maximum Kyphosis angle ( ° ) as evaluated with the help of surface topography ( Formetric ® -system ) . Results : Lateral deviation ( mm ) decreased significantly after the performance of the physio-logic ® programme and highly significantly in the physio-logic ® ADL posture ; however , it was not significant after completion of the whole rehabilitation programme ( 2.3 vs 0.3 mm in the controls ) . Surface rotation improved at average 1.2 ° in the treatment group and 0.8 ° in the controls while Kyphosis angle did not improve in both groups . Discussion : The physio-logic ® programme has to be regarded as a useful ‘ add on ’ to Scoliosis Rehabilitation with regards to the lateral deviation of the scoliotic trunk . A longitudinal controlled study is necessary to evaluate the long-term effect of the the physio-logic ® programme also with the help of X-rays UNLABELLED The Lyon school has proposed a preparation to brace wearing through an intensive mobilization in order to obtain a better reduction of the braced scoliotic curve . Our aim was to verify this hypothesis . DESIGN A prospect i ve controlled study on consecutive patients having idiopathic scoliosis with brace management . OUTCOME Results after 5 months of brace wearing were review ed by radiographic examination without the brace . TREATMENT SEAS Group exercises according to the protocol SEAS.02 ( Scientific Exercises Approach to Scoliosis , version 2002 ) ; CONT Group various type of exercises . Population . 110 patients ( 34 females ) , 13.5+/-2.4 years , 31.1 degrees + /-11.1 degrees Cobb ( degrees C ) , 14.4 degrees + /-6.0 degrees Bunnell ( degrees B ) . All parameters improved at follow-up in both groups . SEAS had better results than CONT for degrees C. Clinical results ( variations of at least 5 degrees C and 2 degrees B ) were better in SEAS than CONT . This study proves the efficacy of SEAS.02 exercises preparatory for bracing . Bracing demonstrated its short term efficacy The goal of this study is to test the hypothesis that physiotherapy-based intervention can reduce incidence of progression in children with IS . Two independent patient groups matched by age and sex at diagnosis were analysed using the outcome parameter , incidence of progression ( S 5 ° ) . One group was untreated and the other received scoliosis in-patient rehabilitation ( SIR ) . Incidence of progression in groups of untreated patients ranged from 1.5-fold ( 71.2 % vs 46.7 % ) to 2.9-fold ( 55.8 % vs 19.2 % ) higher than in groups of patients treated with SIR , even when SIR-treated groups included patients with more severe curvatures . Statistically , the differences were highly significant . Efforts to test the hypothesis that physical therapies addressing postural imbalance can be used effectively in the treatment of IS have been limited . The results of this study are consistent with the possibility that a supervized programme of exercise-based therapies can reduce incidence of progression in children with IS In a prospect i ve study by the Scoliosis Research Society , 286 girls who had adolescent idiopathic scoliosis , a thoracic or thoracolumbar curve of 25 to 35 degrees , and a mean age of twelve years and seven months ( range , ten to fifteen years ) were followed to determine the effect of treatment with observation only ( 129 patients ) , an underarm plastic brace ( 111 patients ) , and nighttime surface electrical stimulation ( forty-six patients ) . Thirty-nine patients were lost to follow-up , leaving 247 ( 86 per cent ) who were followed until maturity or who were dropped from the study because of failure of the assigned treatment . The end point of failure of treatment was defined as an increase in the curve of at least 6 degrees , from the time of the first roentgenogram , on two consecutive roentgenograms . As determined with use of this end point , treatment with a brace failed in seventeen of the 111 patients ; observation only , in fifty-eight of the 129 patients ; and electrical stimulation , in twenty-two of the forty-six patients . According to survivorship analysis , treatment with a brace was associated with a success rate of 74 per cent ( 95 per cent confidence interval , 52 to 84 ) at four years ; observation only , with a success rate of 34 per cent ( 95 per cent confidence interval , 16 to 49 ) ; and electrical stimulation , with a success rate of 33 per cent ( 95 per cent confidence interval , 12 to 60 ) . ( ABSTRACT TRUNCATED AT 250 WORDS UNLABELLED A new ADL ( Activities of Daily Living ) approach in scoliosis rehabilitation has been design ed . The ADL approach uses Side-Shift , physiologic(R ) , 3D-ADL exercises and Schroth exercises according to current st and ard . It was compared to an exercise based scoliosis rehabilitation that mainly uses Schroth exercises and as an add-on the training of ADL . The ADL approach in practice seems to be easier to teach and the treatment needs fewer theoretical modules leading to a better time-efficiency . Aim of this study was to test whether the gain in time-efficiency is at the loss of outcome . MATERIAL S AND METHODS We studied 13 patients having had a 2 weeks ADL based rehabilitation ( ABR ) and compared their clinical outcome parameters ( surface topograhy & Scoliometer angle ) to a group of 13 diagnosis- , age- , sex- , Cobb-angle and curve pattern-matched controls having a 4 weeks programme of exercise based rehabilitation ( EBR ) only . Average age in the study group was 15 years and average Cobb-angle 39 degrees . RESULTS Lateral deviation in the study group already after 2 weeks of ABR decreased 2 mm ( Formetric ) . Lateral deviation in the control group ( EBR ) decreased 1,9 mm . The changes were not significant . Thoracic as well as lumbar Scoliometer angle decreased highly significantly in both groups ( ABR : 1,8 degrees thoracic , 2,3 degrees lumbar ; EBR : 2,1 degrees thoracic , 2,6 degrees lumbar ) . The differences of outcome between the two groups were not significant . CONCLUSIONS ABR ( 2-week programme ) seems to provide similar results as EBR ( 4-week programme ) . ABR seems to provide a better time efficiency , however a prospect i ve controlled study with a larger sample of patients is desirable before final conclusions can be drawn Current work presents the results of spirometric examinations in 124 children aged 5 to 16 years ( mean age 12.1 years ) suffering from idiopathic scoliosis . Children were treated according to asymmetric respiratory exercises method applied in period of 24 days . Healthy children living in Upper Silesia industrial region were the control group . Examined scoliotic group was characterized by generally mild lung function impairment , although the values of spirometric indexes tended to deplete with time of duration and severity of the scoliosis . Especially the tendency of the forced expiratory volume in first second ( FEV1 ) decrease was apparent , as well as maximal expiratory flows MEF50 and MEF25 , in conjunction with Cobb angle increase . Slight but evident increase of forced vital capacity ( FVC ) and FEV1 was observed as a result of rehabilitation utilizing asymmetric respiratory exercises method Output:	Exercises were also shown to be effective in reducing brace prescription . This study ( like the previously published systematic review s ) showed that PEs can improve the Cobb angles of individuals with AIS and can improve strength , mobility , and balance .
MS21670	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Introduction : Induced sputum is a non‐invasive method , and a useful tool to evaluate inflammatory cells and mediators in the airway lumen in the setting of acute exacerbation of chronic obstructive pulmonary disease ( AE COPD ) . However , the inhalation of hypertonic saline solution to induce sputum may cause a bronchoconstrictive response , so it is important to evaluate the success and safety of sputum induction ( SI ) BACKGROUND Endothelin (ET)-l is a bronchoconstrictor peptide produced in the airways . It has been implicated in the pathogenesis of asthma and virally mediated airway inflammation and may play a role in exacerbations of chronic obstructive pulmonary disease ( COPD ) . METHODS Seventy one patients with COPD were followed prospect ively and sample d for plasma and sputum ET-1 levels when stable and during an exacerbation . Sputum was also examined for cytokines , human rhinovirus , and Chlamydia pneumoniae . RESULTS Plasma ET-1 levels were available for 67 patients with stable COPD ( mean ( SD ) 0.58 ( 0.31 ) pg/ml ) ; 28 pairs of stable-exacerbation plasma sample s had a mean stable ET-1 level of 0.54 ( 0.30 ) pg/ml rising to 0.67 ( 0.35 ) pg/ml at exacerbation ( mean difference 0.13 , 95 % confidence interval ( CI ) 0.04 to 0.21 , p = 0.004 ) . Plasma ET-1 levels in the 67 patients with stable COPD were inversely correlated with baseline forced expiratory volume in one second ( FEV1;r = –0.29 , p = 0.022 ) and forced vital capacity ( FVC ; r = –0.38 , p = 0.002 ) . The change in plasma ET-1 levels during an exacerbation correlated with the change in oxygen saturation ( Sao 2;r = –0.41 , p = 0.036 ) . In 14 stable-exacerbation pairs of sputum sample s median stable ET-1 levels were 5.37 ( 0.97–21.95 ) pg/ml rising to 34.68 ( 13.77–51.95 ) pg/ml during an exacerbation ( mean difference 25.14 , 95 % CI 3.77 to 46.51 , p = 0.028 ) . This increase in sputum ET-1 levels correlated with the increase in plasma ET-1 levels ( r = 0.917 , p = 0.001 ) and sputum interleukin (IL)-6 levels ( r = 0.718 , p = 0.013 ) . CONCLUSIONS Sputum levels of ET-1 rise in COPD patients during an exacerbation and this is reflected by a smaller rise in plasma ET-1 levels . ET-1 may have a role in mediating airway inflammatory changes during exacerbations of COPD STUDY OBJECTIVES The etiologic role of bacterial pathogens isolated from sputum culture in 40 to 50 % of acute exacerbations of chronic bronchitis ( AECB ) is controversial . If bacterial pathogens cause these AECB , they should be associated with greater neutrophilic airway inflammation than pathogen-negative exacerbations . DESIGN This hypothesis was tested by comparing levels of interleukin (IL)-8 , tumor necrosis factor (TNF)-alpha , and neutrophil elastase ( NE ) in 81 sputum sample s obtained from 45 patients with AECB . Four groups were compared . In the first three groups , nontypable Haemophilus influenzae ( n = 20 ) , Haemophilus parainfluenzae ( n = 27 ) , and Moraxella catarrhalis ( n = 14 ) were isolated as sole pathogens , respectively . In the fourth group , only normal flora was isolated ( n = 20 ) . Paired sample s , obtained from individual patients at different times , that differed in their culture results were also compared . SETTING An outpatient research clinic at a Veterans Affairs Medical Center . PATIENTS These patients were participating in a prospect i ve , longitudinal study of the dynamics of bacterial infection in chronic bronchitis , for which they were seen in the study clinic on a monthly basis as well as when they were experiencing symptoms suggestive of AECB . INTERVENTIONS None . MEASUREMENTS AND RESULTS H influenzae exacerbations were associated with significantly higher sputum IL-8 , TNF-alpha , and NE . M catarrhalis exacerbations demonstrated significantly higher sputum TNF-alpha and NE when compared to pathogen-negative exacerbations . H parainfluenzae-associated exacerbations had an inflammatory profile similar to pathogen-negative exacerbations . Sputum elastase level distinguished bacterial from nonbacterial AECB and correlated with clinical severity of the AECB . CONCLUSIONS Increased airway inflammation associated with isolation of H influenzae and M catarrhalis supports an etiologic role of these pathogens in AECB Background Non-invasive phenotyping of chronic respiratory diseases would be highly beneficial in the personalised medicine of the future . Volatile organic compounds can be measured in the exhaled breath and may be produced or altered by disease processes . We investigated whether distinct patterns of these compounds were present in chronic obstructive pulmonary disease ( COPD ) and clinical ly relevant disease phenotypes . Methods Breath sample s from 39 COPD subjects and 32 healthy controls were collected and analysed using gas chromatography time-of-flight mass spectrometry . Subjects with COPD also underwent sputum induction . Discriminatory compounds were identified by univariate logistic regression followed by multivariate analysis : 1 . principal component analysis ; 2 . multivariate logistic regression ; 3 . receiver operating characteristic ( ROC ) analysis . Results Comparing COPD versus healthy controls , principal component analysis clustered the 20 best-discriminating compounds into four components explaining 71 % of the variance . Multivariate logistic regression constructed an optimised model using two components with an accuracy of 69 % . The model had 85 % sensitivity , 50 % specificity and ROC area under the curve of 0.74 . Analysis of COPD subgroups showed the method could classify COPD subjects with far greater accuracy . Models were constructed which classified subjects with ≥2 % sputum eosinophilia with ROC area under the curve of 0.94 and those having frequent exacerbations 0.95 . Potential biomarkers correlated to clinical variables were identified in each subgroup . Conclusion The exhaled breath volatile organic compound profile discriminated between COPD and healthy controls and identified clinical ly relevant COPD subgroups . If these findings are vali date d in prospect i ve cohorts , they may have diagnostic and management value in this disease Background : Chronic obstructive pulmonary disease ( COPD ) is characterised by an abnormal inflammatory response mainly to cigarette smoke that flares up during exacerbations of the disease ( E COPD ) . Reduced activity of histone deacetylases ( HDAC ) contributes to enhanced inflammation in stable COPD . It was hypothesised that HDAC activity is further reduced during E COPD and that theophylline , an HDAC activator , potentiates the anti-inflammatory effect of steroids in these patients . A study was performed to investigate HDAC activity during E COPD and the effects of theophylline on the anti-inflammatory effects of steroids in a r and omised single-blind controlled study . Methods : 35 patients hospitalised with E COPD and treated according to international guidelines ( including systemic steroids ) were r and omised to receive or not to receive low-dose oral theophylline ( 100 mg twice daily ) . Before treatment and 3 months after discharge , HDAC and nuclear factor-κB ( NF-κB ) activity in sputum macrophages , the concentration of nitric oxide in exhaled air ( eNO ) and total antioxidant status ( TAS ) , tumour necrosis factor α ( TNFα ) , interleukin (IL)-6 and IL8 levels in sputum supernatants were measured . Results : Patients receiving st and ard therapy showed decreased NF-κB activity , eNO concentration and sputum levels of TNFα , IL6 and IL8 , as well as increased TAS during recovery of E COPD , but HDAC activity did not change . The addition of low-dose theophylline increased HDAC activity and further reduced IL8 and TNFα concentrations . Conclusions : During E COPD , low-dose theophylline increases HDAC activity and improves the anti-inflammatory effects of steroids . Trial registration number : Although inflammatory changes are found throughout the airways of patients with chronic bronchitis , the mechanisms of the pathogenesis of chronic bronchitis are still unclear . The aim of this study was to investigate airways inflammation in patients with and without an exacerbation of bronchitis . Thirteen chronic bronchitic patients and nine normal subjects were studied . Eight of the patients were studied under baseline conditions ( B ) , and five during an exacerbation of bronchitis ( E ) . Bronchoscopy and bronchoalveolar lavage ( BAL ) with cytological analysis were performed , and the levels of granulocyte/macrophage colony-stimulating factor ( GM-CSF ) were determined in sera and in BAL supernatants by a solid phase enzyme immunoassay . Compared with patients under baseline conditions , chronic bronchitic patients with an exacerbation had increased numbers of BAL neutrophils ( 10+/-3 and 83+/-18x10(3 ) cells x mL(-1 ) , respectively ; p<0.0001 ) and of BAL eosinophils ( 1.9+/-0.5 and 6.7/-1.9x10(3 ) cells x mL(-1 ) , respectively ; p=0.014 ) . Patients with chronic bronchitis , as a whole , had significantly increased levels of BAL GM-CSF compared to control subjects ( 36+/-5 and 19+/-4 pg x mL(-1 ) , respectively ; p=0.035 ) , and similar levels of serum GM-CSF . Serum levels of GM-CSF were markedly increased in chronic bronchitic patients with an exacerbation , as compared with patients under baseline conditions ( 1.4+/-0.4 and 13+/-1 pg x mL(-1 ) , respectively ; p < 0.0001 ) . BAL levels of GM-CSF were also increased in chronic bronchitic patients with an exacerbation ( 25+/-5 and 54+/-8 pg x mL(-1 ) , respectively ; p=0.009 ) . During exacerbations of chronic bronchitis there are changes in the cell population s in bronchoalveolar lavage of patients consistent with a recruitment of polymorphonuclear leucocytes in the airway lumen . The increased levels of granulocyte/macrophage colony-stimulating factor might suggest a role for this cytokine in the inflammatory processes of chronic bronchitis The effects of broad-spectrum antibiotic and placebo therapy in patients with chronic obstructive pulmonary disease in exacerbation were compared in a r and omized , double-blinded , crossover trial . Exacerbations were defined in terms of increased dyspnea , sputum production , and sputum purulence . Exacerbations were followed at 3-day intervals by home visits , and those that resolved in 21 days were design ated treatment successes . Treatment failures included exacerbations in which symptoms did not resolve but no intervention was necessary , and those in which the patient 's condition deteriorated so that intervention was necessary . Over 3.5 years in 173 patients , 362 exacerbations were treated , 180 with placebo and 182 with antibiotic . The success rate with placebo was 55 % and with antibiotic 68 % . The rate of failure with deterioration was 19 % with placebo and 10 % with antibiotic . There was a significant benefit associated with antibiotic . Peak flow recovered more rapidly with antibiotic treatment than with placebo . Side effects were uncommon and did not differ between antibiotic and placebo Background : Chronic obstructive pulmonary disease ( COPD ) is characterized by airway inflammation and is associated with acute exacerbations . Macrolide antibiotics have been shown to exhibit anti-inflammatory effects in some chronic airway inflammatory diseases . Objective : The aim of this study was to assess the effect of treatment with erythromycin on airway inflammation and health outcome in COPD patients . Methods : We conducted a r and omized , placebo-controlled , double-blind trial of erythromycin for a period of 6 months . Thirty-six COPD patients were r and omized to treatment with oral erythromycin ( 125 mg , three times/day ) or placebo . The primary outcomes were neutrophil number in sputum and exacerbations . Results : Thirty-one patients completed the study . At the end of treatment , neutrophil counts in the sputum were significantly decreased in the group treated with erythromycin compared with placebo-treated patients ( p = 0.005 ) . Total cells in the sputum and neutrophil elastase in sputum supernatant were also significantly decreased in those treated with erythromycin compared with the placebo group ( p = 0.021 and p = Output:	Among the clinical ly relevant molecules , those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery , as well as for directing towards an etiological diagnosis . In conclusion , pulmonary biomarkers have the potential to provide information on the mechanisms underlying E COPD , and several correlate with clinical variables and outcomes .
MS21671	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This is the first study to investigate the associations of IGF-1 , IGF-2 and IGFBP-3 concentrations with the risk of colorectal cancer in prospect ively collected blood sample s from an Oriental population . Between 1986 and 1989 serum sample s were collected at baseline from 18 244 men , aged 45–65 years , without a history of cancer and living in Shanghai , China . IGF-1 , IGF-2 and IGFBP-3 were measured in the serum of 135 men who developed colorectal cancer over 12 years of follow-up and 661 control subjects drawn from the cohort , who were matched to the index cases by neighbourhood of residence , age , and year and month of sample collection . Serum IGF-1 was not associated with risk of colorectal cancer . IGF-2 and IGFBP-3 , on the other h and , exhibited statistically significant , positive associations with colorectal cancer risk when cases were confined to those diagnosed within a relatively short time period after enrolment ( within 8 years ) . After adjustment for body mass index , cigarette smoking and alcohol intake , men in the highest versus the lowest quintile of IGF-2 and IGFBP-3 showed odds ratios of 2.74 ( 95 % Cl = 1.67–4.50 ; 2-sided P for trend = 0.0008 ) and 2.85 ( 95 % Cl = 1.69–4.81 ; 2-sided P for trend = 0.01 ) , respectively . Our data thus suggest that circulating IGF-2 and IGFBP-3 can serve as early indicators of impending colorectal cancer . © 2001 Cancer Research Campaign There is some evidence that glucose and other factors related to glucose metabolism , such as insulin and insulin-like growth-factors ( IGFs ) may contribute to breast cancer development . The present study analyzed the hypothesis that serum glucose , insulin levels , and IGF-I pattern are associated with breast cancer using a nested case-control study . Between 1987 and 1992 , 10,786 women ages 35 - 69 were recruited in a prospect i ve study in Italy . Women with history of cancer and on hormone therapy were excluded at baseline . At recruitment , blood sample s were collected after a 12-h fast between 7:30 and 9:00 a.m. from all of the study participants . After 5.5 years , 144 breast cancer cases were identified among the participants of the cohort . Four matched controls were chosen for each breast cancer case from members of the cohort who did not develop breast cancer during the follow-up period . In premenopausal women , glucose was associated with breast cancer risk : the age , body mass index , and reproductive variable adjusted relative risk ( RR ) for the highest quartile of serum glucose versus the lowest was 2.8 [ 95 % confidence interval ( CI ) , 1.2 - 6.5 ] , and P for trend was 0.02 . Insulin showed a weaker association with breast cancer , the adjusted RR of the highest quartile versus the lowest was 1.7 ( 95 % CI , 0.7 - 4.1 ) , and P for trend was 0.14 , whereas the adjusted RR of the highest quartile of IGF-I was 3.1 ( 95 % CI , 1.1 - 8.6 ) , and P for trend was 0.01 . Increased levels of insulin-like growth factor binding protein-3 (IGFBP)-3 were related to breast cancer risk : the adjusted RR for the highest quartile was 2.1 ( 95 % CI , 0.95 - 4.75 ) , and P for trend was 0.02 . In postmenopausal women , the associations of glucose , insulin , and IGF-1 pattern were associated with breast cancer risk in heavier subjects characterized by a body mass index higher than 26 . These results indicate that chronic alteration of glucose metabolism is related to breast cancer development Blood concentrations of insulin-like growth factor-I ( IGF-I ) and insulin-like growth factor binding protein-3 ( IGFBP-3 ) have recently been associated with breast cancer risk , notably in women who developed breast cancer at a young age . Prospect i ve studies published so far , however , were relatively small and odds ratio ( OR ) estimates imprecise . We present the results of a large prospect i ve case-control study nested within the European Prospect i ve Investigation into Cancer and Nutrition on total IGF-I , IGFBP-3 and breast cancer risk including 1081 incident cases of invasive breast cancer and 2098 matched control subjects . Increasing IGF-I and IGFBP-3 concentrations were associated with a significant increase in breast cancer risk in women who developed breast cancer after 50 years of age ( highest vs lowest quintile OR 1.38 ( 95 % confidence interval ( CI ) 1.02 - 1.86 ) , P = 0.01 , and 1.44 ( 95 % CI 1.04 - 1.98 ) , P = 0.01 , respectively ) , but no relationship was observed in younger women ( OR = 1.03 ( 95 % CI 0.60 - 1.77 ) , P = 0.81 for IGF-I , and OR = 0.92 ( 95 % CI 0.50 - 1.70 ) , P = 0.69 for IGFBP-3 ) . There was , however , significant heterogeneity in the relationship of breast cancer with serum IGF-I and IGFBP-3 levels depending on the time interval between blood donation and tumor diagnosis . A reduction in breast cancer risk with increasing IGF-I concentrations was observed in cases with a diagnosis of cancer less than 2 years after blood donation , ( OR = 0.76 ( 95 % CI 0.57 - 1.03 ) ) , while an increase in risk was observed for women with a later diagnosis ( above or equal to two years after blood collection , OR = 1.51 ( 95 % CI 1.19 - 1.91 ) ) . A similar pattern was observed for IGFBP-3 . This study confirms previous findings for an association of serum IGF-I and IGFBP-3 concentrations with breast cancer risk , particularly for women with a later diagnosis of cancer , but it does not support the hypothesis of an involvement of IGF-I in younger women BACKGROUND Insulin-like growth factor I ( IGF-I ) stimulates cell proliferation and inhibits apoptosis in the lung and other tissues by interacting with the IGF-I receptor . The major binding protein for IGF-I , insulin-like growth factor-binding protein 3 ( IGFBP-3 ) , modulates the effects of IGF-I but also inhibits cell growth and induces apoptosis independent of IGF-I and its receptor . In a prospect i ve study of men in Shanghai , China , we examined the association between serum levels of IGF-I and IGFBP-3 and the subsequent risk of lung cancer . METHODS From 1986 to 1989 , serum was collected from 18,244 men aged 45 - 64 years living in Shanghai without a history of cancer . We analyzed IGF-I and IGFBP-3 levels in serum from 230 case patients who developed incident lung cancer during follow-up and from 740 control subjects . RESULTS Among 230 case patients and 659 matched control subjects , increased IGF-I levels were not associated with increased risk of lung cancer . However , for subjects in the highest quartile relative to the lowest quartile of IGFBP-3 , the odds ratio ( OR ) for lung cancer , adjusted for smoking and IGF-I , was 0.50 ( 95 % confidence interval [ CI ] = 0.25 to 1.02 ) . When the analysis was restricted to ever smokers ( 184 case patients and 344 matched control subjects ) , the OR for lung cancer in men in the highest quartile of IGFBP-3 relative to those in the lowest quartile , adjusted for smoking and IGF-I , was 0.41 ( 95 % CI = 0.18 to 0.92 ) . CONCLUSIONS In this prospect i ve study of Chinese men , higher serum levels of IGF-I did not increase the risk of lung cancer . However , subjects with higher serum levels of IGFBP-3 were at reduced risk of lung cancer . This finding is consistent with experimental data that indicate that IGFBP-3 can inhibit cellular proliferation and induce apoptosis independent of IGF-I and the IGF-I receptor Insulin-like growth factor (IGF)-I induces growth in pancreatic cancer cells and blockade of the IGF-I receptor has antitumour activity . The association of plasma IGF-I and IGF binding protein-3 ( IGFBP-3 ) with pancreatic cancer risk has been investigated in two small studies , with conflicting results . We conducted a nested case – control study within four large , prospect i ve cohorts to investigate whether prediagnostic plasma levels of IGF-I , IGF-II , and IGFBP-3 were associated with pancreatic cancer risk . Plasma levels in 212 cases and 635 matched controls were compared by conditional logistic regression , with adjustment for other known pancreatic cancer risk factors . No association was observed between plasma levels of IGF-I , IGF-II , or IGFBP-3 and incident diagnosis of pancreatic cancer . Relative risks for the highest vs the lowest quartile of IGF-I , IGF-II , and IGFBP-3 were 0.94 ( 95 % confidence interval ( CI ) , 0.60–1.48 ) , 0.96 ( 95 % CI , 0.61–1.52 ) , and 1.21 ( 95 % CI , 0.75–1.92 ) , respectively . The relative risk for the molar ratio of IGF-I and IGFBP-3 , a surrogate measure for free IGF-I , was 0.84 ( 95 % CI , 0.54–1.31 ) . Additionally , no association was noted in stratified analyses or when requiring longer follow-up . In four prospect i ve cohorts , we found no association between the risk of pancreatic cancer and prediagnostic plasma levels of IGF-I , IGF-II , or IGFBP-3 BACKGROUND Insulin-like growth factor-I ( IGF-I ) is a potent mitogen for normal and neoplastic cells , whereas IGF-binding protein-3 ( IGFBP-3 ) inhibits cell growth in many experimental systems . Acromegalics , who have abnormally high levels of growth hormone and IGF-I , have higher rates of colorectal cancer . We therefore examined associations of plasma levels of IGF-I and IGFBP-3 with the risk of colorectal cancer in a prospect i ve case-control study nested in the Physicians ' Health Study . METHODS Plasma sample s were collected at baseline from 14916 men without diagnosed cancer . IGF-I , IGF-II , and IGFBP-3 were assayed among 193 men later diagnosed with colorectal cancer during 14 years of follow-up and among 318 age- and smoking-matched control subjects . All P values are two-sided . RESULTS IGFBP-3 levels correlated with IGF-I levels ( r=.64 ) and with IGF-II levels ( r=.90 ) . After controlling for IGFBP-3 , age , smoking , body mass index ( weight in kg/[height in m]2 ) , and alcohol intake , men in the highest quintile for IGF-I had an increased risk of colorectal cancer compared with men in the lowest quintile ( relative risk [RR]=2.51 ; 95 % confidence interval [CI]=1.15 - 5.46 ; P for trend = .02 ) . After controlling for IGF-I and other covariates , men with higher IGFBP-3 had a lower risk ( RR=0.28 ; 95 % CI=0.12 - 0.66 ; P for trend = .005 , comparing extreme quintiles ) . The associations were consistent during the first and the second 7-year follow-up intervals and among younger and older men . IGF-II was not associated with risk . CONCLUSIONS Our findings suggest that circulating IGF-I and IGFBP-3 are related to future risk of colorectal cancer Insulin-like growth factors ( IGFs ) may play a role in prostate growth , hyperplasia , and malignancy . High plasma IGF-I has been associated with increased prostate cancer risk . In a prospect i ve , cohort , case-control study in the Baltimore Longitudinal Study on Aging population , we examined prostate volume by magnetic resonance imaging , and prostate-specific antigen ( PSA ) , IGF-I , IGF-II , and IGF-binding protein-3 ( IGFBP-3 ) in sera obtained approximately 9 yr before diagnosis of prostate cancer in cases ( n = 72 ) or age-matched controls ( n = 127 ) and in 76 additional Baltimore Longitudinal Study on Aging men ( normal subjects ) with measured prostate volumes and no prostate cancer . We calculated adjusted odds ratios ( OR ) by logistic regression , relative risks for significant ORs , and receiver operator curves for prostate cancer , using serum measures alone and in combination . Adjusted ORs for the high vs. low tertile were : for IGF-I , 3.1 [ confidence interval ( CI ) , 1.1 - Output:	Our meta- analysis provides comprehensive support for a role of circulation IGF-I and IGF-II in the etiology of CRC
MS21672	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To evaluate the sound localization capabilities of patients with unilateral , profound sensorineural hearing loss who had been treated with either a bone-anchored hearing device ( Baha BP100 ) or a TransEar 380-HF bone-conduction hearing device . STUDY DESIGN Nonr and omized , prospect i ve study . SETTING Tertiary referral private practice . PATIENTS Patients with unilateral , profound sensorineural hearing loss treated with a BP100 ( n = 10 ) or a TransEar ( n = 10 ) device . Patients wore the hearing device for at least 1 month and had normal hearing in the contralateral ear . Ten patients with normal , bilateral hearing were used for control . INTERVENTIONS Sound localization of a 3-second recorded sound with and without a TransEar or Baha device was assessed using an array of 7 speakers at head level separated by approximately 45 degrees . The recorded sounds were that of a barking dog or a police siren . R and omized trials of 4 presentations per speaker were given for each hearing condition . MAIN OUTCOME MEASURES Sound localization was assessed by the accuracy in response and the generalized laterality of response . RESULTS The mean accuracy of speaker localization was 24 % and 26 % for the aided condition using the BP100 and TransEar devices , respectively . The mean accuracy of laterality judgment was 59 % and 69 % for the aided condition using the BP100 and TransEar devices , respectively . These results were only slightly better than chance . There was no statistical difference in localization accuracy or laterality judgment between the BP100 and TransEar groups . CONCLUSION Neither the BP100 nor the TransEar device improved sound localization accuracy or laterality judgment ability in patients with unilateral , profound sensorineural hearing loss compared with performance in the unaided condition Objective : To investigate the effect of low-frequency attenuation of Bone-Anchored Hearing Aids ( Bahas ) in users with single-sided sensorineural deafness ( SSD ) . The underlying notion is that low-frequency sounds up to approximately 1500 Hz reach the contralateral ear without significant attenuation and that Bahas tend to show more distortion at lower frequencies . Furthermore , to transmit low frequencies , higher moving masses are needed when compared with high frequencies . Design : A prospect i ve study with 10 adults , experienced Baha Divino users with SSD . Speech underst and ing in noise was measured without Baha and with Baha , with three different setting s of low-frequency attenuation , namely up to 270 , 630 , and 1500 Hz . Tests were performed in two different spatial arrangements . In one placement , speech was emitted from a loudspeaker on the side of the Baha ear and noise from a loudspeaker in front of the listener ( S90N0 ) . In the other placement , the sound sources were switched ( S0N90 ) . Participants rated the subjective sound quality of the two most extreme Baha setting s using analog visual scales after a short acclimatization time of 15 mins . Results : In setting S90N0 , the use of a Baha improved speech underst and ing in noise significantly ( average improvement 2.8 to 3.1 dB , p = 0.006 ) . These improvements did not vary significantly with the chosen low-frequency attenuation . In setting S0N90 , a smaller but detrimental effect of the Baha was found ( −0.9 to −1.7 dB , p = 0.006 to 0.03 ) . This detrimental effect was significantly smaller at the highest cutoff frequency of 1500 Hz than at 270 Hz ( p = 0.013 ) . At the cutoff frequency of 270 Hz , loudness and reverberation were judged higher than at 1500 Hz . There was no significant difference in brightness , softness , clarity , or fullness . Conclusion : High cutoff levels of up to 1500 Hz for low-frequency signals do not compromise the benefit of Baha in SSD for noise arriving from the front and speech presented on the side of the Baha . If noise is presented from the side of the Baha , the detrimental effect on speech underst and ing can be reduced by higher cutoff frequencies . If frequencies < 1500 Hz do not need to be transmitted , lower moving masses of the Baha are required and smaller devices for patients with SSD may be possible BACKGROUND Cochlear implantation ( CI ) has proven in long term prospect i ve trials to reduce significantly incapacitating tinnitus in single sided deafness ( SSD ) . Discussion arises whether electrical stimulation near the round window ( RW ) is also able to reduce tinnitus . AIM to assess whether electrical stimulation of the basal first 4 intracochlear electrodes of a CI could sufficiently reduce tinnitus and to compare these results with stimulation with all CI electrodes . MATERIAL AND METHODS 7 patients who met the criteria of severe tinnitus due to SSD were implanted with a Med-El Sonata Ti100 with a FlexSoftTM or Flex24TM electrode . After 4 weeks only the basal electrode pair ( E12 ) nearest to the RW was activated . Each week the following pair was activated until the 4th pair . Thereafter all electrodes were activated . Tinnitus was assessed before CI surgery and before each electrode pair was activated . When all electrodes were fitted , evaluation was done after 1 , 3 and 6 months . Tinnitus was assessed with Visual Analogue Scale ( VAS ) for loudness , psychoacoustic tinnitus loudness comparison at 1 kHz and Tinnitus Question naire ( TQ ) for the effect on quality of life . To evaluate the natural evolution , a tightly matched control group with severe tinnitus due to SSD was followed prospect ively . RESULTS All the tinnitus outcome measures remained unchanged with 1 , 2 , 3 or 4 activated electrode pairs . With complete CI activation , the tinnitus decreased significantly comparable with earlier reports . Pre-implantation the tinnitus loudness was 8.2/10 on the VAS and was reduced to 4.1/10 6 months postimplantation . Psychometrically the loudness level went from 21.7 dB SL ( SD : 16.02 ) to 7.5 dB SL ( SD : 5.24 ) and the TQ from 60/84 to 39/84 . The non-implanted group had no decrease of the tinnitus , the average VAS remained stable at 8.9/10 throughout the follow-up period of 6 months . CONCLUSION with the current stimulation parameters electrical stimulation in the first 8e10 mm of the basal part of the scala tympani is insufficient to reduce tinnitus . However , stimulation over the complete CI length yields immediate tinnitus reduction confirming earlier results Objective : To longitudinally evaluate short- and long-term subject satisfaction/benefit perception , device usage rates , complication rates , and external device repair rates of bone-anchored hearing aid ( BAHA ) implantation on a cohort of adult subjects with profound unilateral sensorineural hearing loss ( PUSHL ) . Study Design : Prospect i ve clinical trial . Setting : Tertiary referral center . Patients : Fifty-six adults with PUSHL , 21 of which underwent BAHA implantation ( followed for an average of 3.2 years after implantation ; range , 0.8 - 4.6 yr ) . Main Outcome Measures : Short- and long-term satisfaction/benefit perception outcomes consisting of the Glasgow Hearing Aid Benefit Profile , Abbreviated Profile of Hearing Aid Benefit , and Single-Sided Deafness Question naire , including a comparison of results between implanted and nonimplanted subjects . Short- and long-term device usage rates , complications , and device failure issues also were carefully documented . Results : There were statistically significant improvements in nearly all measures of benefit perception documented as well as a high rate of long-term device usage ( 81 % ) . Although satisfaction and benefit perception outcomes generally tended to regress over time when compared with initial short-term outcomes , long-term scores still tended to be significantly improved nevertheless as compared with preoperative levels . Approximately 38 % of implants experienced severe local skin reactions ( Grade 2 and above ) around the implant site at some point throughout the follow-up period , whereas only one ( 4.8 % ) required implant removal . 66.7 % of subjects required repair of their external sound processor . Conclusion : BAHA implantation seems to provide a high level of short- and long-term perceived benefit and satisfaction in subjects with PUSHL and high rate of long-term device usage . Implant site adverse local skin reactions and repairs of the external sound processor were quite common Objectives : One purpose of this investigation was to evaluate the effect of a unilateral bone-anchored hearing aid ( Baha ) on horizontal plane localization performance in single-sided deaf adults who had either a conductive or sensorineural hearing loss in their impaired ear . The use of a 33-loudspeaker array allowed for a finer response measure than has previously been used to investigate localization in this population . In addition , a detailed analysis of error patterns allowed an evaluation of the contribution of r and om error and bias error to the total rms error computed in the various conditions studied . A second purpose was to investigate the effect of stimulus duration and head-turning on localization performance . Design : Two groups of single-sided deaf adults were tested in a localization task in which they had to identify the direction of a spoken phrase on each trial . One group had a sensorineural hearing loss ( SNHL group ; N = 7 ) , and the other group had a conductive hearing loss ( CHL group ; N = 5 ) . In addition , a control group of four normal-hearing adults was tested . The spoken phrase was either 1250 msec in duration ( a male saying “ Where am I coming from now ? ” ) or 341 msec in duration ( the same male saying “ Where ? ” ) . For the longer- duration phrase , subjects were tested in conditions in which they either were or were not allowed to move their heads before the termination of the phrase . The source came from one of nine positions in the front horizontal plane ( from −79 ° to + 79 ° ) . The response range included 33 choices ( from −90 ° to + 90 ° , separated by 5.6 ° ) . Subjects were tested in all stimulus conditions , both with and without the Baha device . Overall rms error was computed for each condition . Contributions of r and om error and bias error to the overall error were also computed . Results : There was considerable intersubject variability in all conditions . However , for the CHL group , the average overall error was significantly smaller when the Baha was on than when it was off . Further analysis of error patterns indicated that this improvement was primarily based on reduced response bias when the device was on ; that is , the average response azimuth was nearer to the source azimuth when the device was on than when it was off . The SNHL group , on the other h and , had significantly greater overall error when the Baha was on than when it was off . Collapsed across listening conditions and groups , localization performance was significantly better with the 1250 msec stimulus than with the 341 msec stimulus . However , for the longer- duration stimulus , there was no significant beneficial effect of head-turning . Error scores in all conditions for both groups were considerably larger than those in the normal-hearing control group . Conclusions : On average , single-sided deaf adults with CHL showed improved localization ability when using the Baha , whereas single-sided deaf adults with SNHL showed a decrement in performance when using the device . These results may have implication s for clinical counseling for patients with unilateral hearing impairment Abstract Conclusion : The bone-anchored hearing aid ( BAHA ) system can offer significant benefits to patients with single-sided deafness ( SSD ) , primarily by lifting the head shadow effect . Objective : To evaluate the efficacy of BAHA for SSD by comparing pre- and postoperative speech , spatial and qualities of hearing scale ( SSQ ) scores . Methods : This was a prospect i ve study conducted within a tertiary auditory implant department . The inclusion criteria were unilateral profound hearing loss with normal or mild high frequency hearing loss in the hearing ear ( pure tone average better than or equal to 25 dBHL measured at 0.5 , 1 , 2 and 3 kHz ) and subjective benefits reported by patients following a home trial with a BAHA Softb and . Patients who met the above criteria and opted for surgery were asked to complete the SSQ question naire . The postoperative SSQ response was collected after at least 6 months of consistent BAHA usage . Results : This study included 25 adult patients ( mean age at implantation 57.5 years ) . There was a statistically significant improvement in the average SSQ score in all three sections of the question naire with the use of the BAHA . Our patients experienced most marked benefits in speech hearing in challenging listening situations . All patients remain consistent users and there has been no explantation to date To investigate the implication s of duration of deafness in the rehabilitation of unilateral deafness utilizing cochlear implantation . From the ongoing prospect i ve cochlear implantation in unilateral deafness study , we looked at five adults who received a cochlear implant for long-term unilateral deafness . Speech perception in noise and subjective evaluation of the benefits of cochlear implantation were measured at 3 , 6 , and 12 months after implantation . The results were analyzed and compared with published data from normal hearing individuals and adults using cochlear implants bilaterally . Analysis of speech perception in noise showed significant improvement for three spatial configurations : speech and noise from the front ( S0/N0 ; P=0.003 ) , speech from the front and noise from the normal hearing ear ( S0/NHE ; P=0.001 ) , speech from the implanted ear , and noise from the normal hearing ear ( SCI/NHE ; P<0.001 ) . The scores obtained at 12 months after surgery improved to values similar to those obtained Output:	Devices that reroute sounds from an ear with a severe to profound hearing loss to an ear with minimal hearing loss may improve speech perception in noise when signals of interest are located toward the impaired ear . However , the same device may also de grade speech perception as all signals are rerouted indiscriminately , including noise . For the same reason , it remains unclear whether cochlear implantation can improve the ability to localize sounds despite restoring bilateral input .
MS21673	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: To explore the efficacy of a mindfulness-based weight loss intervention for women . Sixty-two women ( ages 19 - 64 ; BMI 22.5 - 52.1 ) who were attempting to lose weight were r and omised to an intervention or control condition . The former were invited to attend four 2-h workshops , the latter were asked to continue with their normal diets . Data were collected at baseline , 4 and 6 months . BMI , physical activity , mental health . At 6 months intervention participants showed significantly greater increases in physical activity compared to controls ( p<.05 ) but no significant differences in weight loss or mental health . However , when intervention participants who reported ' never ' applying the workshop principles at 6 months ( n=7 ) were excluded , results showed both significantly greater increases in physical activity ( 3.1 sessions per week relative to controls , p<.05 ) and significantly greater reductions in BMI ( 0.96 relative to controls , equivalent to 2.32 kg , p<0.5 ) . Reductions in BMI were mediated primarily by reductions in binge eating . Despite its brevity , the intervention was successful at bringing about change . Further refinements should increase its efficacy Psychological distress and elevated cortisol secretion promote abdominal fat , a feature of the Metabolic Syndrome . Effects of stress reduction interventions on abdominal fat are unknown . Forty-seven overweight/obese women ( mean BMI = 31.2 ) were r and omly assigned to a 4-month intervention or waitlist group to explore effects of a mindfulness program for stress eating . We assessed mindfulness , psychological distress , eating behavior , weight , cortisol awakening response ( CAR ) , and abdominal fat ( by dual-energy X-ray absorptiometry ) pre- and posttreatment . Treatment participants improved in mindfulness , anxiety , and external-based eating compared to control participants . Groups did not differ on average CAR , weight , or abdominal fat over time . However , obese treatment participants showed significant reductions in CAR and maintained body weight , while obese control participants had stable CAR and gained weight . Improvements in mindfulness , chronic stress , and CAR were associated with reductions in abdominal fat . This proof of concept study suggests that mindfulness training shows promise for improving eating patterns and the CAR , which may reduce abdominal fat over time Background Obesity is a growing epidemic . Weight control interventions can achieve weight loss , but most is regained over time . Stigma and low quality of life are significant problems that are rarely targeted . Purpose A new model aim ed at reducing avoidant behavior and increasing psychological flexibility , has shown to be relevant in the treatment of other chronic health problems and is worth examining for improving the lives of obese persons . Methods Patients who had completed at least 6 months of a weight loss program ( N = 84 ) were r and omly assigned to receive a 1-day , mindfulness and acceptance-based workshop targeting obesity-related stigma and psychological distress or be placed on a waiting list . Results At a 3-month follow-up , workshop participants showed greater improvements in obesity-related stigma , quality of life , psychological distress , and body mass , as well as improvements in distress tolerance , and both general and weight-specific acceptance and psychological flexibility . Effects on distress , stigma , and quality of life were above and beyond the effects due to improved weight control . Mediational analyses indicated that changes in weight-specific acceptance coping and psychological flexibility mediated changes in outcomes . Conclusion Results provide preliminary support for the role of acceptance and mindfulness in improving the quality of life of obese individuals while simultaneously augmenting their weight control efforts The present study utilized an analog paradigm to investigate the effectiveness of two strategies for coping with food cravings , which was theorized to be critical to the maintenance of weight loss . Ninety-eight undergraduate students were given transparent boxes of chocolate Hershey 's Kisses and instructed to keep the chocolates with them , but not to eat them , for 48 h. Before receiving the Kisses , participants were r and omized to receive either ( a ) no intervention , ( b ) instruction in control-based coping strategies such as distraction and cognitive restructuring , or ( c ) instruction in acceptance-based strategies such as experiential acceptance and defusion techniques . Measures included the Power of Food Scale ( PFS ; a measure of psychological sensitivity to the food environment ) , self-report ratings of chocolate cravings and surreptitiously recorded chocolate consumption . Results suggested that the effect of the intervention depended on baseline PFS levels , such that acceptance-based strategies were associated with better outcomes ( cravings , consumption ) among those reporting the highest susceptibility to the presence of food , but greater cravings among those who scored lowest on the PFS . It was observed that craving self-report measures predicted chocolate consumption , and baseline PFS levels predicted both cravings and consumption . Results are discussed in terms of the implication s for weight loss maintenance strategies Objective To determine whether acceptance-based behavioral treatment ( ABT ) would result in greater weight loss than st and ard behavioral treatment ( SBT ) , and whether treatment effects were moderated by interventionist expertise or participants ’ susceptibility to eating cues . Recent research suggests that poor long-term weight control outcomes are due to lapses in adherence to weight control behaviors , and that adherence might be improved by enhancing SBT with acceptance-based behavioral strategies . Design and Methods Overweight participants ( n = 128 ) were r and omly assigned to 40 weeks of SBT or ABT . Results Both groups produced significant weight loss and , when administered by experts , weight loss was significantly higher in ABT than SBT at post-treatment ( 13.17 % v. 7.54 % ) and 6-month follow-up ( 10.98 % v. 4.83 % ) . Moreover , 64 % of those receiving ABT from experts ( v. 46 % for SBT ) maintained at least a 10 % weight loss by follow-up . Moderation analyses revealed a powerful advantage , at follow-up , of ABT over SBT in those potentially more susceptible to eating cues . For participants with greater baseline depression symptomology , weight loss at follow-up was 11.18 % in ABT vs. 4.63 % in SBT ; other comparisons were 10.51 % vs. 6.00 % ( emotional eating ) , 8.29 % v. 6.35 % ( disinhibition ) and 9.70 % v. 4.46 % ( responsivity to food cues ) . Mediation analyses produced partial support for theorized food-related psychological acceptance as a mechanism of action . Conclusions Results offer strong support for the incorporation of acceptance-based skills into behavioral weight loss treatments , particularly among those with greater levels of depression , responsivity to the food environment , disinhibition and emotional eating , and especially when interventions are provided by weight control experts . Trial Registration clinical trials.gov identifier : Most of the extant literature investigating the health effects of mindfulness interventions relies on wait-list control comparisons . The current article specifies and vali date s an active control condition , the Health Enhancement Program ( HEP ) , thus providing the foundation necessary for rigorous investigations of the relative efficacy of Mindfulness Based Stress Reduction ( MBSR ) and for testing mindfulness as an active ingredient . 63 participants were r and omized to either MBSR ( n = 31 ) or HEP ( n = 32 ) . Compared to HEP , MBSR led to reductions in thermal pain ratings in the mindfulness- but not the HEP-related instruction condition ( η(2 ) = .18 ) . There were significant improvements over time for general distress ( η(2 ) = .09 ) , anxiety ( η(2 ) = .08 ) , hostility ( η(2 ) = .07 ) , and medical symptoms ( η(2 ) = .14 ) , but no effects of intervention . Practice was not related to change . HEP is an active control condition for MBSR while remaining inert to mindfulness . These cl aims are supported by results from a pain task . Participant-reported outcomes ( PROs ) replicate previous improvements to well-being in MBSR , but indicate that MBSR is no more effective than a rigorous active control in improving these indices . These results emphasize the importance of using an active control condition like HEP in studies evaluating the effectiveness of MBSR Mindful eating may be an effective intervention for increasing awareness of hunger and satiety cues , improving eating regulation and dietary patterns , reducing symptoms of depression and anxiety , and promoting weight loss . Diabetes self-management education ( DSME ) , which addresses knowledge , self-efficacy , and outcome expectations for improving food choices , also may be an effective intervention for diabetes self-care . Yet few studies have compared the impact of mindful eating to a DSME-based treatment approach on patient outcomes . Adults 35 to 65 years old with type 2 diabetes for ≥1 year not requiring insulin therapy were recruited from the community and r and omly assigned to treatment group . The impact of a group-based 3-month mindful eating intervention ( MB-EAT-D ; n = 27 ) to a group-based 3-month DSME “ Smart Choices ” ( SC ) intervention ( n = 25 ) postintervention and at 3-month follow-up was evaluated . Repeated- measures ANOVA with contrast analysis compared change in outcomes across time . There was no significant difference between groups in weight change . Significant improvement in depressive symptoms , outcome expectations , nutrition and eating-related self-efficacy , and cognitive control and disinhibition of control regarding eating behaviors occurred for both groups ( all p < .0125 ) at 3-month follow-up . The SC group had greater increase in nutrition knowledge and self-efficacy than the MB-EAT-D group ( all p < .05 ) at 3-month follow-up . MB-EAT-D had significant increase in mindfulness , whereas the SC group had significant increase in fruit and vegetable consumption at study end ( all p < .0125 ) . Both SC and MB-EAT-D were effective treatments for diabetes self-management . The availability of mindful eating and DSME-based approaches offers patients greater choices in meeting their self-care needs OBJECTIVES The purpose of this study was to pilot a brief ( 6-week ) group curriculum for providing mindfulness training to obese individuals , called Mindful Eating and Living ( MEAL ) . SETTING AND DESIGN Participants were recruited through a local Young Men 's Christian Association ( YMCA ) in spring 2006 . Data was collected at three time points : baseline , completion of intervention ( 6 weeks ) , and 3-month follow-up ( 12 weeks ) . INTERVENTION Six weekly two-hour group classes ( with two monthly follow-up classes ) . Content included training in mindfulness meditation , mindful eating , and group discussion , with emphasis on awareness of body sensations , emotions , and triggers to overeat . MAIN OUTCOME MEASURES Key variables assessed included changes in weight , body-mass index ( BMI ) , eating behavior , and psychological distress . In addition , physiological markers of cardiovascular risk were evaluated including C-reactive protein ( hsCRP ) , adiponectin , low-density lipoprotein ( LDL ) , and plasminogen activator inhibitor-1 ( PAI-1 ) . RESULTS Ten obese patients enrolled with a mean BMI of 36.9 kg/m² [ SD±6.2 ] . The mean weight was 101 kg/m² and the mean age was 44 years ( SD=8.7 ; range=31 - 62 ) . Compared to baseline data , participants showed statistically significant increases in measures of mindfulness and cognitive restraint around eating , and statistically significant decreases in weight , eating disinhibition , binge eating , depression , perceived stress , physical symptoms , negative affect , and C-reactive protein . CONCLUSIONS This study provides preliminary evidence that a eating focused mindfulness-based intervention can result in significant changes in weight , eating behavior , and psychological distress in obese individuals Recent research has identified that mindfulness meditation in group setting s supports people who are trying to lose weight . The present research investigated mindfulness meditation in group and individual setting s , and explored the potential impact on weight loss and other factors ( i.e. mindfulness , impulsivity , and avoidance ) that may assist or hinder weight loss . Specifically , the hypotheses tested were that the group setting assisted dieters more than the individual setting by reducing weight , cognitive-behavioral avoidance , and impulsivity and by increasing mindfulness . Participants ( n = 170 ) who were trying to lose weight were r and omly assigned to practice meditation for 6 weeks within a group or independently . Measurements in mindfulness , cognitive-behavioral avoidance , impulsivity , and weight occurred twice ( pre- and post-intervention ) . Results indicated that participants in the group setting lost weight and lowered their levels of cognitive-behavioral avoidance , while impulsivity and mindfulness remained stable . On the other h and , participants in the individual condition lost less weight , while there was an increase in cognitive-behavioral avoidance and mindfulness scores , but a decrease in impulsivity . Seeing that benefits and limitations observed in group setting s are not replicated when people meditate alone , this study concluded that mindfulness meditation in individual setting s needs to be used with caution , although there are some potential benefits that could aid future weight loss research Output:	However , studies do not clarify the degree to which changes in mindfulness are a mechanism responsible for weight loss in mindfulness interventions .
MS21674	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: We present a double-blind trial in which a pulsed infrared beam was compared with a placebo in the treatment of myofascial pain in the cervical region . The patients were su bmi tted to 12 sessions on alternate days to a total energy dose of 5 J each . At each session , the four most painful muscular trigger points and five bilateral homometameric acupuncture points were irradiated . Those in the placebo group su bmi tted to the same number of sessions following an identical procedure , the only difference being that the laser apparatus was nonoperational . Pain was monitored using the Italian version of the McGill pain question naire and the Scott-Huskisson visual analogue scale . The results show a pain attenuation in the treated group and a statistically significant difference between the two groups of patients , both at the end of therapy and at the 3-month follow-up examination OBJECTIVE We aim ed to evaluate the effectiveness of laser therapy in myofascial pain syndrome treatment . BACKGROUND DATA Myofascial pain syndrome is a disease that is characterized by hypersensitive points called trigger points found in one or more muscles and /or connective tissues . It can cause pain , muscle spasm , sensitivity , stiffness , weakness , limitation of range of motion and rarely autonomic dysfunction . Physical therapy modalities and exercise are used in the treatment of this frequently encountered disease . METHODS The placebo controlled , prospect i ve , long-term follow up study was planned with 60 patients who had trigger points in their upper trapezius muscles . The patients were divided into three groups r and omly . Stretching exercises were taught to each group and they were asked to exercise at home . Treatment duration was 4 weeks . Placebo laser was applied to group 1 , dry needling to group 2 and laser to group 3 . He-Ne laser was applied to three trigger points in the upper trapezius muscles on both sides with 632.8 nm . The patients were assessed at before , post-treatment , and 6 months after-treatment for pain , cervical range of motion and functional status . RESULTS We observed a significant decrease in pain at rest , at activity , and increase in pain threshold in the laser group compared to other groups . Improvement according to Nottingham Health Profile gave the superiority of the laser treatment . However , those differences among the groups were not observed at 6-month follow up . CONCLUSIONS Laser therapy could be useful as a treatment modality in myofascial pain syndrome because of its noninvasiveness , ease , and short-term application UNLABELLED The dentin hypersensitivity is a painful condition rather prevalent in the general population . There are several ways of treatment for such condition , including the low intensity lasers . The proposal of this study was to verify the effectiveness of the Gallium-Aluminum-Arsenide diode laser in the treatment of this painful condition , using a placebo as control . MATERIAL S AND METHODS Thirty-two patients were selected , 22 females and 10 males , with ages ranging from 20 to 52 years old . The 32 patients were r and omly distributed into two groups , treated and control ; the sample consisted of 68 teeth , 35 in the treated group and 33 in the control group . The treated group was exposed to six laser applications with intervals from 48 to 72 hours , and the control group received , as placebo , applications of a curing light . RESULTS A significant reduction was observed in the pain condition between the initial phase and after six laser applications ; however , such reduction could also be observed for the control group exposed to the placebo . CONCLUSION Therapy with the low intensity Gallium-Aluminum-Arsenide laser - AsGaAl induces a statistically significant reduction in the painful condition after each application and between the beginning and end of treatment , although there was no statistically significant difference between the treated group ( laser ) and the control group ( placebo ) at the end of treatment and after the mediate evaluation results ( after 6 weeks ) , this way impairing the real measurement of laser effectiveness and placebo effect Objective : To investigate the effectiveness of low‐level laser therapy in the treatment of temporom and ibular disorder and to compare treatment effects in myogenic and arthrogenic cases . Methods : Thirty‐five patients were evaluated by magnetic resonance imaging and r and omly allocated to active treatment ( n=20 ) and placebo treatment ( n=15 ) groups . In addition to a daily exercise program , all patients were treated with fifteen sessions of low‐level laser therapy . Pain , joint motion , number of joint sounds and tender points were assessed . Results : Significant reduction in pain was observed in both active and placebo treatment groups . Active and passive maximum mouth opening , lateral motion , number of tender points were significantly improved only in the active treatment group . Treatment effects in myogenic and arthrogenic cases were similar . Conclusion : Low‐level laser therapy can be considered as an alternative physical modality in the management of temporom and ibular disorder The aim of the study was to evaluate the effect of low level laser application on postoperative pain after endodontic surgery in a double blind , r and omized clinical study . Fifty-two healthy adults undergoing endodontic surgery were included into the study . Subsequently to suturing , 26 patients had the operation site treated with an 809 nm-GaAlAs-laser ( oralaser voxx , Oralia GmbH , Konstanz , Germany ) at a power output of 50 mW and an irradiation time of 150 s. Laser treatment was simulated in further 26 patients . Patients were instructed to evaluate their postoperative pain on 7 days after surgery by means of a visual analogue scale ( VAS ) . The results revealed that the pain level in the laser group was lower than in the placebo group throughout the 7 day follow-up period . The differences , however , were significant only on the first postoperative day ( Mann-Whitney U-test , p<0.05 ) . Low level laser therapy can be beneficial for the reduction of postoperative pain . Its clinical efficiency and applicability with regard to endodontic surgery , however require further investigation . This is in particular true for the optimal energy dosage and the number of laser treatments needed after surgery Low-energy laser therapy has been applied in several rheumatoid and soft tissue disorders with varying rates of success . The objective of our study was to investigate the effect of laser therapy on cervical myofascial pain syndrome with a placebo-controlled double-blind prospect i ve study model . It was performed with a total of 53 patients ( 35 females and 18 males ) with cervical myofascial pain syndrome . In group 1 ( n=23 ) , GaAs laser treatment was applied over three trigger points bilaterally and also one point in the taut b and s in trapezius muscle bilaterally with a frequency of 1000 Hz for 2 min over each point once a day for 10 days during a period of 2 weeks . In group 2 ( n=25 ) , the same treatment protocol was given , but the laser instrument was switched off during applications . All patients in both groups were instructed to perform daily isometric exercises and stretching just short of pain for 2 weeks at home . Evaluations were performed just before treatment ( week 0 ) , immediately after ( week 2 ) , and 12 weeks later ( week 14 ) . Evaluation parameters included pain , algometric measurements , and cervical lateral flexion . Statistical analysis was done on data collected from three evaluation stages . The results were evaluated in 48 patients ( 32 females , 16 males ) . Week 2 and week 14 results showed significant improvement in all parameters for both groups . However , comparison of the percentage changes both immediately and 12 weeks after treatment did not show a significant difference relative to pretreatment values . In conclusion , the results of our study have not shown the superiority of GaAs laser therapy over placebo in the treatment of cervical myofascial pain syndrome , but we suggest that further studies on this topic be done using different laser types and dosages in larger patient population BACKGROUND AND OBJECTIVES The efficacy of low level laser therapy ( LLLT ) in myofascial pain syndrome ( MPS ) seems controversial . Our aim was to clarify the effect of LLLT in MPS by using algometry and thermography . STUDY DESIGN / MATERIAL S AND METHODS Sixty-two patients with MPS having an active trigger point in the neck or upper back region were r and omly divided into two equal groups according to therapy applied ( group 1 : LLLT + stretching exercises , group 2 : stretching exercises alone ) . The outcome measures were pain measured with visual analogue scale ( VAS ) , algometry on the trigger point , algometric difference , thermographic difference , and thermal asymmetry . Comparison was made within and between the groups pre- and post-therapeutically and 3 weeks after therapy . RESULTS Mean pain values decreased more significantly in group 1 from baseline to 3 weeks follow up ( 7.54 - 3.06 ) while these values were 7.03 - 5.19 in group 2 ( P < 0.05 ) . Group comparisons revealed significant favorable differences in group 1 patients in terms of all other parameters at the first and the second evaluation post therapeutically ( P < 0.05 ) . CONCLUSIONS LLLT seemed to be beneficial for pain in MPS by using algometry and thermography BACKGROUND AND OBJECTIVES A prospect i ve , double-blind , r and omized , and controlled trial was conducted in patients with chronic myofascial pain syndrome ( MPS ) in the neck to evaluate the effects of infrared low level 904 nm Gallium-Arsenide ( Ga-As ) laser therapy ( LLLT ) on clinical and quality of life ( QoL ) . STUDY DESIGN / PATIENTS AND METHODS The study group consisted of 60 MPS patients . Patients were r and omly assigned to two treatment groups : Group I ( actual laser ; 30 patients ) and Group II ( placebo laser ; 30 patients ) . LLLT continued daily for 2 weeks except weekends . Follow-up measures were evaluated at baseline , 2 , 3 , and 12 weeks . All patients were evaluated with respect to pain at rest , pain at movement , number of trigger points ( TP ) , the Neck Pain and Disability Visual Analog Scale ( NPAD ) , Beck depression Inventory ( BDI ) , and the Nottingham Health Profile ( NHP ) . RESULTS In active laser group , statistically significant improvements were detected in all outcome measures compared with baseline ( P < 0.01 ) while in the placebo laser group , significant improvements were detected in only pain score at rest at the 1 week later of the end of treatment . The score for self-assessed improvement of pain was significantly different between the active and placebo laser groups ( 63 vs. 19 % ) ( P < 0.01 ) . CONCLUSION This study revealed that short-period application of LLLT is effective in pain relief and in the improvement of functional ability and QoL in patients with MPS Cervical dentine hypersensitivity is the most frequent complaint among reported odontalgias . Thus , this study evaluated the effectiveness of two types of lasers ( 660 nm wavelength red , and 830 nm wavelength infrared ) as dentine desensitizers , as well as both the immediate and late therapeutic effects in individuals 25 to 45 years of age . A total of 40 teeth with cervical exposure were treated in 4 sessions . They were divided into 2 groups according to treatment . A 660 nm wavelength red diode laser and an 830 nm wavelength infrared diode laser were used . Dentine sensitivity to cold nociceptive stimulus was evaluated by means of a pain numeric scale from zero to 10 before each treatment session , at 15 and 30 min after irradiation , and in a follow-up period of 15 , 30 and 60 days after the end of treatment . Significant levels of dentinal desensitization were only found in patients ranging in age from 25 to 35 years . The 660 nm red diode laser was more effective than the 830 nm infrared laser and a higher level of desensitization was observed at the 15 and 30 minute post-irradiation examinations . The immediate and late therapeutic effects of the 660 nm red diode laser were more evident in 25 - 35-year-old patients compared with those of the 830 nm infrared diode laser , in terms of the different age groups The efficacy of low-level laser therapy ( LLLT ) in myofascial pain syndrome ( MPS ) seems controversial . A prospect i ve , double-blind , r and omized controlled trial was conducted in patients with chronic MPS in the neck to evaluate the effects of low-level 830-nm gallium arsenide aluminum ( Ga – As – Al ) laser therapy . The study group consisted of 64 MPS patients . The patients were r and omly assigned into two groups . In group 1 ( n = 32 ) , Ga – As – Al laser treatment was applied over three trigger points bilaterally for 2 min over each point once a day for 15 days during a period of 3 weeks . In group 2 ( n = 32 ) , the same treatment protocol was given , but the laser instrument was switched off during applications . All patients in both groups performed daily isometric exercise and stretching exercises for cervical region . Parameters were measured at baseline and after 4 weeks . All patients were evaluated with respect to pain ( at rest , movement , and night ) and assessed by visual analog scale , measurement of active range of motion using an inclinometer and a goniometer , and the neck disability index . In both groups , statistically significant improvements were detected in all outcome measures compared with baseline ( p < 0.05 ) . However , no significant differences were obtained between the two groups ( p > 0.05 ) . In conclusion , although the laser therapy has no superiority over placebo groups in this study , we can not exclude the possibility of effectivity with another treatment regimen including different laser wavelengths and dosages ( different intensity and density and /or treatment interval ) OBJECTIVE To compare the clin Output:	Only limited evidence indicated that LLLT is more effective than placebo , sham laser , and other active treatments
MS21675	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The i.v . bolus administration of 1 alpha hydroxylated vitamin D derivatives is effective in the treatment of uremic hyperparathyroidism . However , few of the published studies of this mode of treatment have been adequately controlled , and recent reports have suggested that p.o . bolus administration may be just as effective . In this study , 16 hemodialysis patients with mild to moderate hyperparathyroidism were assigned , after a 4-wk run-in period , to receive a 6-wk course of either thrice-weekly i.v . or p.o . alfacalcidol ( initial dose , 4 micrograms ) . Then , after a further control period , they received a second 6-wk course , with either p.o . or i.v . alfacalcidol ( whichever was not given in the first treatment period ) . Plasma parathyroid hormone ( PTH ) was measured weekly by the use of an intact hormone assay . Both routes of therapy result ed in a significant suppression of plasma PTH ( P = 0.005 ) and an elevation in plasma ionized calcium ( P = 0.01 ) . The magnitude of the responses was similar for the two treatment phases , as was the relationship between the increment in calcium and the decrement in PTH . The most complete suppression of PTH was seen in those with the greatest increment in plasma calcium . The incidence of hypercalcemia and the mean dose reductions necessary were also similar in the two treatment phases . Oral bolus therapy and i.v . bolus therapy with alfacalcidol are equally effective in suppressing hyperparathyroidism . The postulated advantages of i.v . over p.o . therapy with 1 alpha hydroxylated vitamin D derivatives remain to be confirmed by controlled studies Thirteen patients in the predialysis phase of chronic renal failure ( CRF ) were treated with calcitriol ( 0.25 micrograms/day ) and 12 with placebo . After 1 year of study , an increase in bone mineral density in the calcitriol group measured by dual-energy X-ray absorptiometry was seen for the femoral neck and lumbar spine when compared to the placebo group ( p < 0.001 and p < 0.01 , respectively ) . We conclude that a steady low dose of calcitriol started in the predialysis phase of CRF is beneficial to the patients with CRF . This may be partly due to suppression of secondary hyperparathyroidism Our prospect i ve 1-year study comprises 93 patients of both sexes , various ages and various dialysis duration . Among them , 31 patients with a concentration of Ca in blood under 2.7 mmol/l , a concentration of P under 1.8 mmol/l and a concentration of PTHi over 65 pg/ml ( group 0 ) received calcitriol 0.25 microgramx418p4The control group consisted of patients not receiving calcitriol and having normal Ca and P metabolism ( group 1 ) . The rest of the patients had a concentration of P over 1.8 mmol/l and could not be given calcitriol . A comparison of the dynamics of average plasmic concentrations of Ca , P , AP , PTHi and X-ray changes in group 0 and 1 at the beginning of the investigation and 1 year later was carried out . At the termination of the 1-year treatment , when compared to the initial state , a statistically significant increase in the concentration of Ca ( p < 0.005 ) and in the concentration of P ( p < 0.005 ) was noted in group 0 . The average concentration of PTHi decreased to the desired level , the X-ray changes characteristic of secondary hyperparathyroidism progressed more slowly in group 0 BACKGROUND Intermittent oral or intravenous doses of calcitriol given two or three times per week are commonly used to treat secondary hyperparathyroidism ( secondary HPT ) . This study was undertaken to compare the biochemical and skeletal responses to thrice weekly intraperitoneal ( i.p . ) versus oral doses of calcitriol in children with secondary HPT undergoing peritoneal dialysis ( CCPD ) . METHODS Forty-six patients aged 12.5+/-4.8 years on CCPD for 22+/-25 months were r and omly assigned to treatment with oral ( p.o . ) or i.p . calcitriol for 12 months ; 17 subjects given p.o . calcitriol and 16 subjects given i.p . calcitriol completed the study . Bone biopsies were performed at the beginning and at the end of the study , while determinations of serum and total ionized calcium , phosphorus , alkaline phosphatase , parathyroid hormone ( PTH ) and calcitriol levels were done monthly . RESULTS Serum total and ionized calcium levels were higher in subjects treated with i.p . calcitriol , P < 0.0001 , whereas serum phosphorus levels were higher in those given p.o . calcitriol , P < 0.0001 . For the i.p . group , serum PTH levels decreased from pre-treatment values of 648+/-125 pg/ml to a nadir of 169+/-57 pg/ml after nine months . In contrast , serum PTH levels did not change from baseline values of 670+/-97 pg/ml in subjects given p.o . calcitriol , P < 0.0001 by multiple regression analysis . Serum alkaline phosphatase levels were also lower in patients treated with i.p . calcitriol , P < 0.0001 , but there was no difference between groups in the average dose of calcitriol given thrice weekly . The skeletal lesions of secondary HPT improved in both groups , 33 % of patients developed adynamic bone lesion . CONCLUSION Differences in the bioavailability of calcitriol and /or in phosphorus metabolism may account for the divergent biochemical response to p.o . and i.p . calcitriol Management of secondary hyperparathyroidism is challenging with traditional therapy . The calcimimetic cinacalcet HCl acts on the calcium-sensing receptor to increase its sensitivity to calcium , thereby reducing parathyroid hormone ( PTH ) secretion . This phase 3 , multicenter , r and omized , placebo-controlled , double-blind study evaluated the efficacy and safety of cinacalcet in hemodialysis ( HD ) and peritoneal dialysis ( PD ) patients with PTH > or = 300 pg/ml despite traditional therapy . A total of 395 patients received once-daily oral cinacalcet ( 260 HD , 34 PD ) or placebo ( 89 HD , 12 PD ) titrated from 30 to 180 mg to achieve a target intact PTH ( iPTH ) level of < or = 250 pg/ml . During a 10-wk efficacy assessment phase , cinacalcet was more effective than control for PTH reduction outcomes , including proportion of patients with mean iPTH levels < or = 300 pg/ml ( 46 versus 9 % ) , proportion of patients with > or = 30 % reduction in iPTH from baseline ( 65 versus 13 % ) , and proportion of patients with > or = 20 , > or = 40 , or > or = 50 % reduction from baseline . Cinacalcet had comparable efficacy in HD and PD patients ; 50 % of PD patients achieved a mean iPTH < or = 300 pg/ml . Cinacalcet also significantly reduced serum calcium , phosphorus , and Ca x P levels compared with control treatment . The most common side effects , nausea and vomiting , were usually mild to moderate in severity and transient . Once-daily oral cinacalcet was effective in rapidly and safely reducing PTH , Ca x P , calcium , and phosphorus levels in patients who received HD or PD . Cinacalcet offers a new therapeutic option for controlling secondary hyperparathyroidism in patients with chronic kidney disease on dialysis BACKGROUND Calcium-based phosphate binders may induce tissue calcification , and little is known about their effects on bone density . We compared the effects of a calcium with a non-calcium phosphate binder on both arterial calcification and bone density measured by computed tomography . METHODS Seventy-two adult haemodialysis patients were r and omized to treatment with calcium carbonate ( CC ) or sevelamer ( SEV ) for 2 years . Electron beam CT scans were performed at baseline and at 6 , 12 and 24 months . Serum phosphorus , calcium , calcium x phosphorus product and intact parathyroid hormone ( iPTH ) were measured and other routine laboratory tests were also carried out . RESULTS The average calcium x phosphorus product was similar in the two treatment groups . However , patients receiving CC had significantly lower average iPTH ( P<0.01 ) , were more likely to have hypercalcaemic episodes ( P = 0.03 ) and had significantly greater increases in coronary artery ( CC median 484 , P<0.0001 , SEV median 37 , P = 0.3118 , between-group P = 0.0178 ) and aortic ( CC median 610 , P = 0.0003 , SEV median 0 , P = 0.5966 , between-group P = 0.0039 ) calcification scores . The CC group also had a significant decrease in trabecular bone density ( CC median -6 % , P = 0.0049 , SEV median + 3 % , P = 0.0296 , between-group P = 0.0025 ) . However , there was no significant difference in cortical bone density between the two groups . CONCLUSIONS This 2 year study shows that calcium carbonate use is continuously associated with progressive arterial calcification in haemodialysis patients . In addition , it suggests that it is also associated with decreased trabecular bone density . However , this latter finding requires confirmation by a study specifically devoted to this issue Controversy exists among various studies in regard to the efficacy of oral ( p.o . ) versus parenteral calcitriol . Some studies suggest that intravenous ( i.v . ) calcitriol is superior to p.o . calcitriol for treating renal osteodystrophy in hemodialysis patients ; others suggest that these routes of administration are equivalent . To our knowledge , no large , prospect i ve , r and omized study compares intraperitoneal ( i.p . ) to p.o . calcitriol in adult peritoneal dialysis patients . We conducted a prospect i ve r and omized study in 76 patients ( 38 on i.p . calcitriol and 38 on p.o . calcitriol ) , whom we followed for 48 months . Of the 76 patients , 34 ( 18 in the i.p . group and 16 in the p.o . group ) completed the 48-month study period . Calcitriol dosing was similar in both groups ( 3 - 6 micrograms per week in three divided doses ) . Dose adjustments were made depending on levels of parathyroid hormone ( PTH ) , serum calcium , phosphorus , and calcitriol . No significant difference was seen between the groups in regard to age , sex , race , body mass index , dialysis duration , or cause of ESRD . Neither was any difference in the incidence of peritonitis seen between the groups . In the first 3 - 6 months , PTH decreased equivalently in both groups . The PTH level remained suppressed in the i.p . group throughout the remainder of the study , but , in the p.o . group , PTH returned to its pretreatment level after 3 - 6 months . Mean serum calcium was not different in the two groups . In the p.o . group , a considerably higher mean follow-up phosphorus level ( 6.8 + /- 2.3 mg/dL versus 4.7 + /- 1.4 mg/dL , p = 0.008 ) , PTH level ( 384 + /- 146 pg/mL versus 162 + /- 64 pg/mL ; p = 0.005 ) , and alkaline phosphatase level ( 178 + /- 37 IU/L versus 72 + /- 21 IU/L , p = 0.02 ) were seen as compared to the i.p . group . In the i.p . group , resolution of osteodystrophy occurred in all patients at the end of the study ; in the p.o . group , 5 patients maintained or developed osteodystrophy by the end of the study ( p = 0.016 ) . We conclude that i.p . calcitriol is more effective than pulse p.o . calcitriol in lowering PTH and alkaline phosphatase levels and in resolving renal osteodystrophy , and that i.p . calcitriol is associated with a lower incidence of hyperphosphatemia and elevated Ca x PO4 byproduct BACKGROUND Higher doses of calcitriol are effective in lowering markedly elevated 1,84 PTH levels of patients with renal secondary hyperparathyroidism . It has not been established , however , whether prophylactic administration of low doses of calcitriol prevents an increase of 1,84 PTH without causing side-effects , i.e. hypercalcaemia , hypercalciuria , or hyperphosphataemia . STUDY DESIGN We carried out a placebo-controlled , double-blind prospect i ve multicentre trial over 12 months in 45 patients with mild to moderate renal failure . Criteria for inclusion were S-creatinine 1.4 mg/dl and 1,84 PTH > 6 pmol/l ( normal 6 ) . Calcitriol 0.125 microgram/day per os was compared with placebo . The patients received Output:	Calcimimetics used in patients receiving haemodialysis or peritoneal dialysis are more effective than placebo in controlling secondary hyperparathyroidism ( reduced parathyroid hormone levels , calcium levels and phosphorus levels ) . All phosphate binders are effective in controlling hyperphosphatemia but different doses are to be used with different agents to achieve similar targets . Dosing needs to be adjusted according to phosphorus levels . Vitamin D and its analogues are recommended in CKD patients , although there is no significant evidence of superiority of individual agents in head-to-head comparisons . Available evidence suggests that calcimimetics , phosphate binders and vitamin D or its analogues are effective in the treatment of secondary hyperparathyroidism .
MS21676	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A r and omized , double-blind , placebo-controlled study of brain-derived neurotrophic factor ( rhBDNF ) was conducted in 30 patients with insulin-treated diabetes mellitus , with obligatory abnormalities of sural nerve conduction studies and vibration perception threshold ( VPT ) at the great toe on recruitment . Nine patients received placebo , 11 rhBDNF ( 25 microg/ kg ) and 10 rhBDNF ( 100 microg/kg ) s.c . daily for 3 months , and were assessed at days 0 , 8 , 15 , 29 , 43 , 57 and 85 with nerve conduction and quantitative sensory and autonomic tests including VPT , thermal and light touch thresholds , and cutaneous axon-reflexes . No statistically significant differences were found among the 3 treatment groups between baseline and day 85 values . To examine possible reasons for lack of effect , post hoc analysis was performed . In the subset of patients with abnormal but detectable cool detection threshold ( CDT ) at baseline , there was improvement of CDT at day 85 when compared to baseline in the treated ( p < 0.02 ) but not placebo group . Further , from days 43 to 85 , in the treated group but not the placebo group , CDT was indistinguishable from a group of matched normal subjects ( p > 0.05 ) . Skin biopsies failed to show evidence of structural change ; assessment of innervation of hair follicles , which is partly dependent on BDNF , was not possible because of the marked loss of this end-organ in diabetic neuropathic skin . The only side effects of rhBDNF were infrequent non-painful injection-site skin reactions and increased gut motility at the higher dose . We conclude that further pre clinical studies are warranted before any future clinical trials to see if rhBDNF improves CDT and constipation in diabetics Background : The Norfolk Quality of Life Question naire-Diabetic Neuropathy ( Norfolk QOL-DN ) is a vali date d comprehensive question naire design ed to capture the entire spectrum of DN related to large fiber , small fiber , and autonomic neuropathy not captured in existing instruments . We aim ed to determine if the Norfolk QOL-DN could be used to capture changes in QOL that correlate with nerve fiber-specific objective measures in a placebo-controlled trial of two agents that affect different nerve fibers . Methods : Sixty patients with DN were allocated to treatment on ruboxistaurin ( RBX ) ( n = 18 ) , topiramate ( TPX ) ( n = 18 ) , or placebo ( n = 18 ) . QOL-DN was administered and objective measures of nerve function were performed at entry and end of the study period . Results : Total QOL scores improved significantly in the active treatment groups ( RBX −9.56 ± 4.13 ; TPX −12.22 ± 2.76 ) but not in placebo ( −5.56 ± 3.49 ) . There were differences in nerve function improvement between treatments . Neurological symptom scores ( NSS ) improved with TPX from 5.5 ( 2.3 ) to 4.3 ( 0.65 ) ( p = .007 ) , sensory scores improved with TPX from 15.5 ( 1.79 ) to 8.3 ( 1.19 ) ( p < .001 ) , motor scores did not change , and sensory and motor impairment scores improved with TPX from 18.8 ( 2.15 ) to 12.1 ( 1.71 ) ( p = .003 ) . Total neuropathy scores ( TNS ) improved with TPX from 24.35 ( 2.61 ) to 16.35 ( 2.02 ) ( p = .001 ) . Neuropathy total symptom score−6 ( NTSS−6 ) changes were significant for both treatments : RBX 4.38 ( 0.75 ) to 1.49 ( 0.38 ) ( p < .001 ) and TPX 7.57 ( 1.3 ) to 4.26 ( 0.95 ) ( p = .036 ) . Changes in QOL-DN large fiber subscores correlated ( Spearman 's rank ) significantly with changes in NTSS-6 ( r = 0.55 ; p < .0001 ) , NSS ( r = 0.31 ; p < .04 ) , neuropathy impairment score ( NIS ) ( r = 0.35 ; p < .02 ) , and TNS ( r = 0.48 ; p < .0006 ) . Changes in QOL-DN small fiber subscores correlated significantly with changes in NTSS-6 total scores ( r = 0.40 ; p < .005 ) and intraepidermal nerve fiber density ( IENFD ) ( r = −0.29 ; p < .05 ) . Conclusion : Ruboxistaurin produced significant improvement in large fiber measures while TPX produced significant changes in small fiber measures . The Norfolk QOL-DN tool differentiated between these changes captured in the fiber-specific domains . Correlations were found between objective measures of neuropathy and total QOL , but those with nerve fiber domain scores were modest and reinforce the need to quantify QOL as an endpoint in neuropathy independent of other measures Summary The role of afferent sensory input in neuropathic pain was examined in 2 groups . Peripheral nerve blocks abolished spontaneous and evoked pain in all patients . Systemic lidocaine was more effective in pain due to polyneuropathy than nerve injury . Central sensitization does not act as an autonomous spontaneous pain‐generating mechanism . Peripheral sensory input is critical in maintaining pain after peripheral nerve damage . ABSTRACT Central sensitization after peripheral nerve injury may result in ectopic neuronal activity in the spinal cord dorsal horn , implying a potential autonomous pain‐generating mechanism . This study used peripheral nerve blockade and systemic lidocaine administration , with detailed somatosensory assessment , to determine the contribution of primary afferent input in maintaining peripheral neuropathic pain . Fourteen patients with neuropathic pain ( 7 with unilateral foot pain due to peripheral nerve injury and 7 with bilateral pain in the feet due to distal polyneuropathy ) underwent comprehensive characterization of somatosensory function by quantitative sensory testing . Patients were then administered an ultrasound‐guided peripheral nerve block with lidocaine and intravenous lidocaine infusion in r and omized order . The effect of these interventions on spontaneous pain intensity and on evoked cold , warm , pinprick , and brush responses was assessed at each session . All patients had sensory disturbances at baseline . The peripheral nerve block result ed in a complete abolition of ipsilateral pain within 10 min ( median ) in all patients , with lidocaine plasma concentrations being too low to account for a systemic effect of the drug . Intravenous lidocaine infusion reduced the spontaneous pain by 45.5 % ( ±31.7 % ) , and it reduced mechanical and thermal hypersensitivity in most patients who displayed such signs . However , the improvement in evoked hypersensitivity was not related to the effect of the drug on spontaneous pain intensity . This study demonstrated that regardless of the individual somatosensory phenotype and signs of central sensitization , primary afferent input is critical for maintaining neuropathic pain in peripheral nerve injury and distal polyneuropathy Background Fabry disease is an inborn lysosomal storage disorder which is associated with small fiber neuropathy . We set out to investigate small fiber conduction in Fabry patients using pain-related evoked potentials ( PREP ) . Methods In this case – control study we prospect ively studied 76 consecutive Fabry patients for electrical small fiber conduction in correlation with small fiber function and morphology . Data were compared with healthy controls using non-parametric statistical tests . All patients underwent neurological examination and were investigated with pain and depression question naires . Small fiber function ( quantitative sensory testing , QST ) , morphology ( skin punch biopsy ) , and electrical conduction ( PREP ) were assessed and correlated . Patients were stratified for gender and disease severity as reflected by renal function . Results All Fabry patients ( 31 men , 45 women ) had small fiber neuropathy . Men with Fabry disease showed impaired cold ( p < 0.01 ) and warm perception ( p < 0.05 ) , while women did not differ from controls . Intraepidermal nerve fiber density ( IENFD ) was reduced at the lower leg ( p < 0.001 ) and the back ( p < 0.05 ) mainly of men with impaired renal function . When investigating A-delta fiber conduction with PREP , men but not women with Fabry disease had lower amplitudes upon stimulation at face ( p < 0.01 ) , h and s ( p < 0.05 ) , and feet ( p < 0.01 ) compared to controls . PREP amplitudes further decreased with advance in disease severity . PREP amplitudes and warm ( p < 0.05 ) and cold detection thresholds ( p < 0.01 ) at the feet correlated positively in male patients . ConclusionS mall fiber conduction is impaired in men with Fabry disease and worsens with advanced disease severity . PREP are well-suited to measure A-delta fiber conduction & NA ; The sodium channel blocker oxcarbazepine is efficacious in peripheral neuropathic pain patients , with preserved thermal sensation and some gain of sensory function , that is , the “ irritable nociceptor ” phenotype . & NA ; In neuropathic pain it has been suggested that pain phenotype based on putative pain mechanisms may predict response to treatment . This was a r and omised , double‐blind , placebo‐controlled , and phenotype‐stratified study with 2 6‐week treatment periods of oxcarbazepine ( 1800‐2400 mg ) and placebo . The primary efficacy measure was change in median pain intensity between baseline and the last week of treatment measured on an 11‐point numeric rating scale , and the primary objective was to compare the effect of oxcarbazepine in patients with and without the irritable nociceptor phenotype as defined by hypersensitivity and preserved small nerve fibre function determined by detailed quantitative sensory testing . Ninety‐seven patients with peripheral neuropathic pain due to polyneuropathy , surgical or traumatic nerve injury , or postherpetic neuralgia were r and omised . The intention‐to‐treat population comprised 83 patients : 31 with the irritable and 52 with the nonirritable nociceptor phenotype . In the total sample , oxcarbazepine relieved pain of 0.7 points ( on a numeric rating scale 0‐10 ; 95 % confidence interval [ CI ] 0.4‐1.4 ) more than placebo ( P = 0.015 ) and there was a significant interaction between treatment and phenotype of 0.7 ( 95 % CI 0.01‐1.4 , P = 0.047 ) . The number needed to treat to obtain one patient with more than 50 % pain relief was 6.9 ( 95 % CI 4.2‐22 ) in the total sample , 3.9 ( 95 % CI 2.3‐12 ) in the irritable , and 13 ( 95 % CI 5.3‐∞ ) in the nonirritable nociceptor phenotype . In conclusion , oxcarbazepine is more efficacious for relief of peripheral neuropathic pain in patients with the irritable vs the nonirritable nociceptor phenotype Summary Topical clonidine significantly reduces pain associated with diabetic neuropathy in subjects with functional nociceptors in the affected skin , as revealed by testing with topical capsaicin . Abstract A length‐dependent neuropathy with pain in the feet is a common complication of diabetes ( painful diabetic neuropathy ) . It was hypothesized that pain may arise from sensitized‐hyperactive cutaneous nociceptors , and that this abnormal signaling may be reduced by topical administration of the α2‐adrenergic agonist , clonidine , to the painful area . This was a r and omized , double‐blind , placebo‐controlled , parallel‐group , multicenter trial . Nociceptor function was measured by determining the painfulness of 0.1 % topical capsaicin applied to the pretibial area of each subject for 30 minutes during screening . Subjects were then r and omized to receive 0.1 % topical clonidine gel ( n = 89 ) or placebo gel ( n = 90 ) applied 3 times a day to their feet for 12 weeks . The difference in foot pain at week 12 in relation to baseline , rated on a 0–10 numerical pain rating scale ( NPRS ) , was compared between groups . Baseline NPRS was imputed for missing data for subjects who terminated the study early . The subjects treated with clonidine showed a trend toward decreased foot pain compared to the placebo‐treated group ( the primary endpoint ; P = 0.07 ) . In subjects who felt any level of pain to capsaicin , clonidine was superior to placebo ( P < 0.05 ) . In subjects with a capsaicin pain rating ⩾2 ( 0–10 , NPRS ) , the mean decrease in foot pain was 2.6 for active compared to 1.4 for placebo ( P = 0.01 ) . Topical clonidine gel significantly reduces the level of foot pain in painful diabetic neuropathy subjects with functional ( and possibly sensitized ) nociceptors in the affected skin as revealed by testing with topical capsaicin . Screening for cutaneous n Output:	The results indicate that epidermal nerve fiber loss , in isolation , is not a useful indicator of painful symptoms or their severity in DSP . Intraepidermal nerve fiber density correlated reasonably well with neuropathy scores on tools assessing signs and symptoms ( such as the Michigan Neuropathy Screening Instrument and the Total Neuropathy Score ) , but less so with symptom measures only . Among various psychophysical sensory measures , warmth detection and heat pain thresholds correlated best with intraepidermal nerve fiber density , particularly when assessed at the same anatomical site .
MS21677	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND It has been extensively shown , mainly in US population s , that sugar-sweetened beverages ( SSBs ) are associated with increased risk of type 2 diabetes ( T2D ) , but less is known about the effects of artificially sweetened beverages ( ASBs ) . OBJECTIVE We evaluated the association between self-reported SSB , ASB , and 100 % fruit juice consumption and T2D risk over 14 y of follow-up in the French prospect i ve Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale-European Prospect i ve Investigation into Cancer and Nutrition cohort . DESIGN A total of 66,118 women were followed from 1993 , and 1369 incident cases of T2D were diagnosed during the follow-up . Cox regression models were used to estimate HRs and 95 % CIs for T2D risk . RESULTS The average consumption of sweetened beverages in consumers was 328 and 568 mL/wk for SSBs and ASBs , respectively . Compared with nonconsumers , women in the highest quartiles of SSB and ASB consumers were at increased risk of T2D with HRs ( 95 % CIs ) of 1.34 ( 1.05 , 1.71 ) and 2.21 ( 1.56 , 3.14 ) for women who consumed > 359 and > 603 mL/wk of SSBs and ASBs , respectively . Strong positive trends in T2D risk were also observed across quartiles of consumption for both types of beverage ( P = 0.0088 and P < 0.0001 , respectively ) . In sensitivity analyses , associations were partly mediated by BMI , although there was still a strong significant independent effect . No association was observed for 100 % fruit juice consumption . CONCLUSIONS Both SSB consumption and ASB consumption were associated with increased T2D risk . We can not rule out that factors other than ASB consumption that we did not control for are responsible for the association with diabetes , and r and omized trials are required to prove a causal link between ASB consumption and T2D BACKGROUND The accumulation of abdominal fat increases risk of metabolic disorders and premature death . There is a dearth of prospect i ve data on the association between caloric beverage consumption and surrogate markers of abdominal adiposity . OBJECTIVE The aim of this study was to assess the relation between consumption of nonalcoholic caloric beverages , including soft drinks , fruit juice , whole milk , and skim and low-fat milk , and changes in waist circumference ( WC ) and odds of 10-y incidence of abdominal obesity . METHODS We conducted a prospect i ve , population -based study of 2181 Spanish men and women aged 25 - 74 y who were followed from 2000 to 2009 . We measured weight , height , and WC , and recorded data on diet and leisure-time physical activity ( LTPA ) with the use of vali date d question naires . We fit multivariable linear and logistic regression models . RESULTS A 100 kcal increase in soft drink consumption was associated with a 1.1 cm increase in WC ( P = 0.018 ) after 10 y of follow-up . Substitution of 100 kcal of soft drinks with 100 kcal of whole milk or 100 kcal of juice was associated with a 1.3 cm ( 95 % CI : 0.3 , 2.4 ) and 1.1 cm ( 95 % CI : 0.03 , 2.2 ) decrease in WC , respectively . Increasing consumption of soft drinks from baseline to follow-up led to WC gain compared with maintaining nonconsumption . Greater soft drink consumption was positively associated ( P = 0.029 ) with increased odds of 10-y incidence of abdominal obesity . CONCLUSION Adults ' consumption of soft drinks was associated with increased WC and odds of 10-y incidence of abdominal obesity . This association was moderate but consistent in all statistical models Objective To evaluate the effectiveness of a school-based intervention involving the families and teachers that aim ed to promote healthy eating habits in adolescents ; the ultimate aim of the intervention was to reduce the increase in body mass index ( BMI ) of the students . Design Paired cluster r and omized school-based trial conducted with a sample of fifth grade rs . Setting Twenty classes were r and omly assigned into either an intervention group or a control group . Participants From a total of 574 eligible students , 559 students participated in the study ( intervention : 10 classes with 277 participants ; control : 10 classes with 282 participants ) . The mean age of students was 11 years . Intervention Students attended 9 nutritional education sessions during the 2010 academic year . Parents/guardians and teachers received information on the same subjects . Main Outcome Measurement Changes in BMI and percentage of body fat . Results Intention-to-treat analysis showed that changes in BMI were not significantly different between the 2 groups ( β = 0.003 ; p = 0.75 ) . There was a major reduction in the consumption of sugar-sweetened beverages and cookies in the intervention group ; students in this group also consumed more fruits . Conclusion Encouraging the adoption of healthy eating habits promoted important changes in the adolescent diet , but this did not lead to a reduction in BMI gain . Strategies based exclusively on the quality of diet may not reduce weight gain among adolescents . Trial Registration Clinical trials.gov NCT01046474 The aim of the present study was to examine the associations of sugary drink consumption and its substitution with alternative beverages with body weight gain among young children predisposed to future weight gain . Secondary analysis of the Healthy Start Study , a 1·5-year r and omised controlled trial design ed to prevent overweight among Danish children aged 2 - 6 years ( n 366 ) , was carried out . Multivariate linear regression models were used to investigate the associations of beverage consumption with change in body weight ( Δweight ) or BMI ( Δ BMI ) z-score . Substitution models were used to extrapolate the influence of replacing sugary drinks with alternative beverages ( water , milk and diet drinks ) on Δweight or Δ BMI z-score . Sugary drink intake at baseline and substitution of sugary drinks with milk were associated with both Δweight and Δ BMI z-score . Every 100 g/d increase in sugary drink intake was associated with 0·10 kg and 0·06 unit increases in body weight ( P=0·048 ) and BMI z-score ( P=0·04 ) , respectively . Substitution of 100 g/d sugary drinks with 100 g/d milk was inversely associated with Δweight ( β=-0·16 kg ; P=0·045 ) and Δ BMI z-score ( β=-0·07 units ; P=0·04 ) . The results of this study suggest that sugary drink consumption was associated with body weight gain among young children with high predisposition for future overweight . In line with the current recommendations , sugary drinks , whether high in added or natural sugar , should be discouraged to help prevent childhood obesity . Milk may be a good alternative to sugary drinks with regard to weight management among young obesity-predisposed children OBJECTIVES To examine the relationship between diet soda ( DS ) intake ( DSI ) and long-term waist circumference ( WC ) change ( ΔWC ) in the biethnic San Antonio Longitudinal Study of Aging ( SALSA ) . DESIGN Prospect i ve cohort study . SETTING San Antonio , Texas , neighborhoods . PARTICIPANTS SALSA examined 749 Mexican-American and European-American individuals aged 65 and older at baseline ( baseline , 1992 - 96 ) ; 474 ( 79.1 % ) survivors completed follow-up 1 ( FU1 , 2000 - 01 ) , 413 ( 73.4 % ) completed FU2 ( 2001 - 03 ) , and 375 ( 71.0 % ) completed FU3 ( 2003 - 04 ) . Participants completed a mean of 2.64 follow-up intervals , for 9.4 total follow-up years . MEASUREMENTS DSI , WC , height , and weight were measured at outset and at the conclusion of each interval : baseline , FU1 , FU2 , and FU3 . RESULTS Adjusted for initial WC , demographic characteristics , physical activity , diabetes mellitus , and smoking , mean interval ΔWC of DS users ( 2.11 cm , 95 % confidence interval ( CI ) = 1.45 - 2.76 cm ) was almost triple that of nonusers ( 0.77 cm , 95 % CI = 0.29 - 1.23 cm ) ( P < .001 ) . Adjusted interval ΔWCs were 0.77 cm ( 95 % CI = 0.29 - 1.23 cm ) for nonusers , 1.76 cm ( 95 % CI = 0.96 - 2.57 cm ) for occasional users , and 3.04 cm ( 95 % CI = 1.82 - 4.26 cm ) for daily users ( P = .002 for trend ) . This translates to ΔWCs of 0.80 inches for nonusers , 1.83 inches for occasional users , and 3.16 for daily users over the total SALSA follow-up . In subanalyses stratified for selected covariates , ΔWC point estimates were consistently higher in DS users . CONCLUSION In a striking dose-response relationship , increasing DSI was associated with escalating abdominal obesity , a potential pathway for cardiometabolic risk in this aging population Objective Sales of regular soda are declining , but sales of other sweetened beverages , such as sports drinks , are increasing . Our objective was to determine the prospect i ve associations between sports drinks and body mass index ( BMI ) gains among adolescents and young adults . Design and Methods We prospect ively followed 4,121 females and 3,438 males in the Growing Up Today Study II , aged 9–16 in 2004 , from across the United States . Data was collected by question naire in 2004 , 2006 , 2008 , and 2011 . Servings per day of various beverages were assessed with a food frequency question naire . Results Among the girls , each serving per day of sports drink predicted an increase of 0.3 BMI units ( 95 % confidence interval ( CI ) CI 0.03–0.54 ) more than their peers over the next 2–3 years . Among the males , each serving of sports drinks predicted a 0.33 BMI ( 95 % CI 0.09 , 0.66 ) increase . In addition , boys who increased their intake over the 2–3 year interval gained significantly more than their peers during the same time interval . Conclusions Intake of sports drinks predicted larger increases in BMI among both females and males . Our results suggest that school policies focused on obesity prevention should be augmented to restrict sports drinks Sugar-sweetened beverages ( SSB ) contribute to excessive weight gain through added energy intake . Replacing SSB with water is one strategy that has shown promise in helping lower excessive energy intake . Using nationally representative data from US adults ( n = 19,718 ) from NHANES 2007–2012 we examine the impact of replacing SSB with water on Healthy Beverage Index ( HBI ) scores and obesity prevalence . Replacing an 8-ounce serving of SSB with water lowered the percent of energy from beverages from 17 % to 11 % ( among those consuming 1 serving SSB/day ) . Reductions in the percent energy from beverages were observed across all SSB consumption groups ( 1–2 servings/day and > 2 servings/day ) . Among adults there was a 9 % to 21 % improvement in HBI score when one serving of water replaced one serving of SSB . Using previously published r and omized controlled trials ( RCT ) and meta-analyses of measured weight loss we also predicted a reduction in the prevalence of obesity ( observed : 35.2 % ; predicted 33.5%–34.9 % , p < 0.05 ) and increase in the prevalence of normal weight ( observed : 29.7 % ; high weight loss : 31.3 % , p < 0.05 ) . Our findings provide further epidemiologic evidence that water in the place of SSB can be used as a strategy to limit energy intake and help individuals meet beverage intake recommendations Background / Objectives : This longitudinal study describes the relationship between young children ’s screen time , dietary habits and anthropometric measures . The hypothesis was that television viewing and other screen activities at baseline result in increased consumption of sugar-sweetened beverages ( SSB ) and increased BMI , BMI z-score and waist to height ratio ( WHtR ) two years later . A second hypothesis was that SSB consumption mediates the association between the screen activities and changes in the anthropometric measures .Subjects/ Methods : The study is a part of the prospect i ve cohort study IDEFICS ( “ Identification and prevention of dietary and lifestyle-induced health effects in children and infants ” ) , investigating diet , lifestyle and social determinants of obesity in 2 to 9-year-olds in eight European countries ( baseline n=16 225 , two-year follow-up ; n=11 038 ) . Anthropometry was objective ly measured , and behaviours were parent-reported . Output:	Conclusion : Recent evidence suggests that SSB consumption is positively associated with or has an effect on obesity indices in children and adults .
MS21678	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE We tested the effects of a 10-week group-based cognitive-behavioral stress management/expressive-supportive therapy intervention ( CBSM+ ) and a time-matched individual psychoeducational condition for 330 women with AIDS reporting moderate to poor baseline quality of life ( QOL ) . The goal of this study was to examine treatment effects on total QOL and 11 QOL domains from baseline to post-intervention follow-up . METHODS Participants were assessed at baseline , r and omized to a treatment condition ( individual psychoeducation condition n=180 , group-based CBSM+ condition n=150 ) , participated in the intervention for 10 weeks and assessed again within 4 weeks following the intervention . QOL was measured using the Medical Outcomes Study -HIV-30 . RESULTS QOL scores increased over the course of both interventions for the total QOL score and three QOL domains : cognitive functioning , health distress and overall health perceptions . While women in the CBSM+ group condition showed a significant improvement in mental health QOL from pre- to post-intervention , women in the individual condition did not change . No changes were observed for energy/fatigue , health transition , single-item overall QOL , pain , physical well-being , role functioning or social functioning in either condition . CONCLUSION Results suggest that group-based CBSM+ and individual psychoeducational interventions are effective at improving certain aspects of QOL and that group-based CBSM+ may be particularly effective at increasing QOL related to mental health in this population of women with AIDS Background Stress management interventions can reduce symptoms of distress as well as modulate certain immune system components in persons infected with human immunodeficiency virus ( HIV ) . These effects may occur in parallel with reductions in hypothalamic-pituitary-adrenal ( HPA ) axis hormones such as cortisol , which has been related in other work to a down-regulation of immune system components relevant to HIV infection . The present study tested the effects of a multimodal cognitive-behavioral stress management ( CBSM ) intervention on 24-hour urinary free cortisol levels and distressed mood in symptomatic HIV+ gay men . Methods Symptomatic HIV-infected gay men who were r and omized to either a 10-week group-based CBSM intervention or a 10-week wait-list period provided psychological responses and urine sample s pre-post intervention . Results Of the 59 participants providing matched question naire data , men assigned to CBSM ( n=40 ) showed significantly lower posttreatment levels of self-reported depressed affect , anxiety , anger , and confusion than those in the wait-list control group ( n=19 ) . Among the 47 men providing urine sample s ( 34 CBSM , 13 controls ) , those assigned to CBSM revealed significantly less cortisol output as compared to controls . At the individual level , depressed mood decreases paralleled cortisol reductions over this period across the entire sample . Conclusion A time-limited CBSM intervention reduced distress symptoms and urinary free cortisol output in symptomatic HIV+ gay men and greater reductions in some aspects of distress , especially depressed mood , paralleled greater decreases in cortisol over the intervention period . If persisting stressors and depressed mood contribute to chronic HPA axis activation in HIV-infected persons , then interventions such as CBSM , which teaches them to relax , alter cognitive appraisal s , use new coping strategies , and access social support re sources , may decrease distress and depressed mood and normalize HPA axis functioning We wished to determine the short-term safety and efficacy of a Chinese medicinal herb preparation in treating symptoms of human immunodeficiency virus ( HIV ) infection in a 12-week r and omized , double-blind , placebo-controlled clinical trial in a University-affiliated acquired immunodeficiency syndrome ( AIDS ) clinic at a public general hospital . Thirty adults with symptomatic HIV infection , no previous AIDS-defining diagnosis , and CD4 + counts of 0.200 - 0.499 x 10(9)/L ( 200 - 499/mm3 ) received 28 tablets each day of either a st and ardized oral preparation of 31 Chinese herbs or a cellulose placebo . Primary outcome measures were changes in life satisfaction , perceived health , and number and severity of symptoms . Other outcomes included adherence , and changes in weight , CD4 + count , depression , anxiety , physical and social function , and mental health . Two placebo- and no herb-treated subjects had mild adverse events ( AE ) . Subjects on both arms reported taking 94 % of prescribed tablets . No differences between treatment groups reached the p < 0.05 level . Life satisfaction improved in herb-treated [ + 0.86 , 95 % confidence interval ( CI ) : + 0.29 , + 1.43 ] but not in placebo-treated subjects ( + 0.20 , 95 % CI -0.35 , + 0.75 ) . Number of symptoms was reduced in subjects receiving herbs ( -2.2 , 95 % CI -4.1 , -0.3 ) but not in those receiving placebo ( -0.3 , 95 % CI -3.2 , + 2.7 ) . There were trends toward greater improvements among herb-treated subjects on all symptom subscales except dermatologic . Believing that one was receiving herbs was strongly associated with reporting that the treatment had helped ( p < 0.005 ) , but not with changes in life satisfaction or symptoms . There were improvements in life satisfaction and symptoms among subjects receiving the herbal therapy . Whether Chinese herbs are effective in the management of symptomatic HIV infection can be adequately addressed only by larger trials of longer duration Assigned r and omly 28 neonates born to HIV-positive mothers to a massage therapy or control group . The treatment infants were given three 15-minute massages daily for 10 days . The massaged group showed superior performance on almost every Brazelton newborn cluster score and had a greater daily weight gain at the end of the treatment period unlike the control group who showed declining performance CONTEXT Peripheral neuropathy is common in persons infected with the human immunodeficiency virus ( HIV ) but few data on symptomatic treatment are available . OBJECTIVE To evaluate the efficacy of a st and ardized acupuncture regimen ( SAR ) and amitriptyline hydrochloride for the relief of pain due to HIV-related peripheral neuropathy in HIV-infected patients . DESIGN R and omized , placebo-controlled , multicenter clinical trial . Each site enrolled patients into 1 of the following 3 options : ( 1 ) a modified double-blind 2 x 2 factorial design of SAR , amitriptyline , or the combination compared with placebo , ( 2 ) a modified double-blind design of an SAR vs control points , or ( 3 ) a double-blind design of amitriptyline vs placebo . SETTING Terry Beirn Community Programs for Clinical Research on AIDS ( HIV primary care providers ) in 10 US cities . PATIENTS Patients with HIV-associated , symptomatic , lower-extremity peripheral neuropathy . Of 250 patients enrolled , 239 were in the acupuncture comparison ( 125 in the factorial option and 114 in the SAR option vs control points option ) , and 136 patients were in the amitriptyline comparison ( 125 in the factorial option and 11 in amitriptyline option vs placebo option ) . INTERVENTIONS St and ardized acupuncture regimen vs control points , amitriptyline ( 75 mg/d ) vs placebo , or both for 14 weeks . MAIN OUTCOME MEASURE Changes in mean pain scores at 6 and 14 weeks , using a pain scale ranging from 0.0 ( no pain ) to 1.75 ( extremely intense ) , recorded daily . RESULTS Patients in all 4 groups showed reduction in mean pain scores at 6 and 14 weeks compared with baseline values . For both the acupuncture and amitriptyline comparisons , changes in pain score were not significantly different between the 2 groups . At 6 weeks , the estimated difference in pain reduction for patients in the SAR group compared with those in the control points group ( a negative value indicates a greater reduction for the " active " treatment ) was 0.01 ( 95 % confidence interval [ CI ] , -0.11 to 0.12 ; P=.88 ) and for patients in the amitriptyline group vs those in the placebo group was -0.07 ( 95 % CI , -0.22 to 0.08 ; P=.38 ) . At 14 weeks , the difference for those in the SAR group compared with those in the control points group was -0.08 ( 95 % CI , -0.21 to 0.06 ; P=.26 ) and for amitriptyline compared with placebo was 0.00 ( 95 % CI , -0.18 to 0.19 ; P=.99 ) . CONCLUSIONS In this study , neither acupuncture nor amitriptyline was more effective than placebo in relieving pain caused by HIV-related peripheral neuropathy CONTEXT Alternative medicine or complementary remedies that have not been scientifically tested are nonetheless widely used to treat chronic illnesses , particularly if curative options are limited . OBJECTIVES To assess the effectiveness of Chinese medicinal herbs in reducing symptoms and improving the quality of life of HIV-infected persons . DESIGN Prospect i ve , placebo-controlled double-blind study . SETTING University-based HIV outpatient clinic . PATIENTS 68 HIV-infected adults with CD4 cell counts < 0.5 x 10(9)/L. INTERVENTION Participants were r and omized to receive four daily doses of seven pills containing a st and ardized preparation of 35 Chinese herbs or placebo for 6 months . MAIN OUTCOME MEASURES Symptoms , HIV disease progression , HIV-1 RNA plasma viral loads , CD4 and CD8 cell counts , and scores on st and ard question naires for quality of life , depression , anxiety , and coping . RESULTS Intervention and placebo groups were equivalent at baseline regarding , respectively , previous antiretroviral therapy ( 74 % versus 79 % ) , median CD4 cell counts ( 0.20 x 10(9)/L versus 0.25 x 10(9)/L ) , and median HIV-1 plasma viral loads ( 35,612 copies/ml versus 52,027 copies/ml ) . At enrollment , none of the study subjects was seriously ill or depressed , and average coping and quality of life scores were in the normal range . In all , 53 ( 78 % ) participants completed the study . Patients taking Chinese herbs reported significantly more gastrointestinal disturbances ( 79 % versus 38 % ; p = .003 ) than those receiving placebo . No therapy-related toxicities were observed . At completion of the study , no significant differences between the intervention and placebo groups were found regarding plasma viral loads , CD4 cell counts , symptoms , and psychometric parameters . HIV-1 RNA level was unchanged at study end . Among participants who were not on concomitant antiretroviral therapy , median CD4 cell counts declined by 0.05 x 10(9)/L in both the intervention and placebo groups . CONCLUSIONS This st and ardized formulation of Chinese herbs for HIV-infected individuals did not improve quality of life , clinical manifestations , plasma virus loads , or CD4 cell counts . The data suggest that this formulation of Chinese herbs is not effective when administered in a Western medicine setting In this pilot study , 20 HIV-infected children , 6 to 12 years of age , were r and omly assigned into therapeutic touch ( TT ) and mimic TT groups . The effectiveness of TT in reducing anxiety was evaluated . The self-report measure , the A-State Anxiety subscale of the Spielberger State-Trait Anxiety Inventory For Children , was administered before and immediately after interventions . As predicted , the TT intervention result ed in lower overall mean anxiety scores , whereas the mimic TT did not . These findings provide preliminary support for the use of TT in reducing the state anxiety of children with HIV infection This study tested the effects of a 7-week individual self-management and coping skills training program on various measures of health and well-being of persons with HIV/AIDS . Forty men and women were r and omly assigned the treatment or wait-list control group . Treated participants showed significant posttreatment changes on all four major measures of mood , coping , and health attitudes . Treatment significantly improved coping strategies as measured by the use and effective measures of the Jalowiec Coping Scale and several of its subscales , including decreases in use of emotive , fatalistic , and palliative coping styles . Psychological mood was improved , as measured by the Profile of Moods Total Mood Disturbance ( POMS TMD ) score and specific subscales of the POMS , which were targeted in the intervention ( e.g. , Anger ) . Treated participants also showed significant increases on the Internal subscale of the Health Attribution Test Twenty-nine gay men ( 20 HIV+ , 9 HIV- ) received daily massages for one month . A subset of 11 of the HIV+ subjects served as a within subject control group ( one month with and without massages ) . Major immune findings for the effects of the month of massage included a significant increase in Natural Killer Cell number , Natural Killer Cell Cytotoxicity , soluble CD8 , and the cytotoxic subset of CD8 cells . There were no changes in HIV disease progression markers ( CD4 , CD4/CD8 ratio , Beta-2 microglobulin , neopterin ) . Major Output:	The results suggest that stress management may prove to be an effective way to increase the quality of life . For all other treatments , data are insufficient for demonstrating effectiveness .
MS21679	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Approximately 10%–15 % of people with diabetes develop at least one foot ulcer during their lifetime . Treatment of diabetic foot ulcers ( DFUs ) represents a significant economic burden . Enzymatic debridement with clostridial collagenase ointment ( CCO ) can be used to remove necrotic tissue from wounds . This study examined the impact of CCO as an effective adjunct therapy to serial sharp debridement ( SSD ) and assessed the cost-effectiveness of CCO compared with st and ard DFU treatments over 1 year . Methods Adults 18 years or older with a diagnosis of type 1 or type 2 diabetes who had a neuropathic DFU were enrolled in a 12-week , r and omized , open-label trial . Patients were r and omly assigned to either treatment with CCO + SSD or to investigator-selected supportive care + SSD ( Control ) . A 3-state Markov model with a 1-week cycle length was developed using wound-closure rates from the trial to estimate the number of healed-wound weeks and the expected DFU cost per patient . The 3 states included unhealed , healed , and death . Results were extrapolated to 1 year to estimate the number of healed-wound weeks per treatment and the average cost to achieve epithelialization . The perspective of the analysis was that of the payer , specifically , the third party payer . Results The study sample included 55 patients ( 28 in CCO group ; 27 Control ) . The majority were men ( 74.5 % ) with a mean age of 57.9 years . Projected healing rates were greater for the CCO + SSD group compared to Control ( 89 % vs. 80 % , respectively ) . The expected number of epithelialized weeks accumulated over 1 year was 25 % greater in the CCO + SSD group than for Control ( 35 vs. 28 weeks , respectively ) . Over a 1-year time horizon , the expected cost per DFU was greater in the Control group than the CCO group ( $ 2,376 vs. $ 2,099 , respectively ) . The estimated cost per ulcer-free week was 40 % higher for Control ( $ 85/closed-wound week ) than for CCO + SSD ( $ 61/closed-wound week ) . Conclusions CCO + SSD therapy is a cost-effective method of debridement in the management of patients with DFUs , providing better outcomes at a lower cost . Further high quality trials are needed to confirm this finding . Trial registration This study was registered at Clinical Trials.gov as NCT01408277 BACKGROUND Despite significant advances , the treatment of diabetic foot ulcers ( DFUs ) remains a major therapeutic challenge for clinicians , surgeons , and other health care professionals . There is an urgent need for new strategies with clinical ly effective interventions to treat DFUs to reduce the burden of care in an efficient and cost-effective way . OBJECTIVE This r and omized trial evaluated and compared the clinical effectiveness , tolerability , and costs of clostridial collagenase ointment ( CCO ) debridement to that of debridement using saline moistened gauze ( SMG ) and selective sharp debridement for the treatment of DFUs . METHODS R and omized , controlled , parallel group , multicenter , open-label , 12-week study of 48 patients with neuropathic DFUs r and omized to 4 weeks of treatment with either CCO or SMG after baseline surgical debridement . The primary end point was the condition of the ulcer bed at the end of treatment as measured using a st and ardized wound assessment tool . Secondary end points were the percentage of reduction in wound area and therapeutic response rates . Adverse events were monitored for the tolerability analysis . In addition , a comparative cost-effectiveness analysis was performed from the perspective of the Centers for Medicare and Medicaid Services as a payer . RESULTS Both the CCO and SMG groups had significantly improved wound assessment scores after 4 weeks of treatment ( CCO , -2.5 , P = 0.007 ; SMG , -3.4 , P = 0.006 ) . Only CCO treatment result ed in a statistically significant decrease from baseline in the mean wound area at the end of treatment ( P = 0.0164 ) and at the end of follow-up ( P = 0.012 ) . In addition , the CCO group exhibited a significantly better response rate at the end of follow-up compared with the SMG group ( 0.92 vs 0.75 , P < 0.05 ) . Reported adverse events were similar between the 2 treatment groups . None of the reported adverse events were considered to be related to treatment . The economic analysis indicated that the direct mean costs per responder in the physician office setting of care were $ 832 versus $ 1042 for the CCO group versus the SMG group , whereas the direct mean costs per responder in the hospital outpatient department setting were $ 1607 versus $ 1980 . CONCLUSIONS CCO treatment provides equivalent debridement of DFUs similar to SMG while fostering better progress toward healing as measured by decreasing wound area over time and improved response rates at the end of follow-up . In addition , CCO yields a more favorable cost-effectiveness ratio in both the physician office and hospital outpatient department setting s of care . Clinical Trials.gov identifier : NCT01056198 INTRODUCTION The purpose of this study is to determine the cost-effectiveness of collagenase ointment relative to autolysis with a hydrogel dressing when debriding necrotic pressure ulcers in a long-term care setting . METHODS A Markov decision process model with 2 states ( necrotic nonviable wound bed transitioning to a granulated viable wound bed ) was developed using data derived from a prospect i ve , r and omized , 6-week , single-center trial of 27 institutionalized subjects with pressure ulcers that were ≥ 85 % necrotic nonviable tissue . Direct medical costs from the payer perspective included study treatments , wound treatment supplies , and nursing time . Clinical benefit was measured as " granulation days " and was derived from the time-dependent debridement rates of the alternative products . RESULTS The average cost per patient for 42 days of pressure ulcer care was $ 1,817 in 2012 for the collagenase group and $ 1,611 for the hydrogel group . Days spent with a granulated wound were 3.6 times higher for collagenase ( 23.4 vs 6.5 ) than with the hydrogel . The estimated cost per granulation day was > 3.2 times higher for hydrogel ( $ 249 ) vs collagenase ( $ 78 ) . CONCLUSIONS In this economic analysis based on a r and omized , controlled clinical trial , collagenase ointment result ed in a faster time to complete debridement and was more cost-effective than hydrogel autolysis for pressure ulcers in a long-term care setting . Even though collagenase ointment has a higher acquisition cost than hydrogel , the clinical benefit offsets the initial cost difference , result ing in lower cost per granulation day to the nursing home over the course of the 42-day analysis UNLABELLED The role of maintenance debridement in wound healing has been well described , yet little is known regarding comparative methods and associated outcomes with this process when using collagenase or hydrogel . OBJECTIVE Evaluation of maintenance debridement and wound closure with collagenase compared to hydrogel in institutionalized adults with pressure ulcers from time of necrotic tissue removal up to 84 days from enrollment . METHODS This second phase of a rollover evaluation enrolled only subjects who successfully completed phase 1 ( previously reported ) from time of necrotic tissue debridement . Subjects received daily dressing changes with either hydrogel or collagenase followed by a st and ard semiocclusive dressing to evaluate wound-healing parameters and wound closure from initial enrollment to day 84 . Investigators blinded to r and omization evaluated weekly wound photographs using a digital planimetry software package for wound-healing parameters . Additionally , Pressure Ulcer Scale for Healing ( PUSH ) © Tool and wound bed scores ( WBS ) were monitored . RESULTS Eleven of 13 subjects from the collagenase group entered into phase 2 , with 4 of the 14 subjects from the hydrogel group . One subject from each group was eliminated within the first week of phase 2 . All subjects ( n = 3 ) in the hydrogel group reached complete epithelialization with a mean of 32.6 days . Nine of 10 subjects in the collagenase group reached completed epithelialization with a mean of 45 days . An independent sample s t test showed no statistical significance between the 2 groups ( P = 0.121 ) in days to healing . A Fisher 's exact test performed on the primary endpoint of complete epithelialization also demonstrated no significant difference in outcomes between the groups ( P = 0.99 ) . Mean WBS at the onsetof phase 2 was 13.7 ( range 12 - 16 ) , and the PUSH Tool mean score was 1.0 ( range 0 - 3 ) . In aggregating phase 1 and phase 2 data , a difference in the closure rates at the end of the study , 69 % ( collagenase ) vs 21 % ( hydrogel ) , was statically significant ( P = 0.0213 ) using a Fisher 's exact test . CONCLUSION Facilitating maintenance debridement by either collagenase or hydrogel can be used to complete wound closure when used in conjunction with a vali date d predictive wound-healing tool that closely monitors therapy . This study showed statistical significance in favor of collagenase when evaluating closure rates from the onset of the pressure ulcer . OBJECTIVE A r and omised clinical trial ( n = 42 ) compared the effectiveness of two approaches to debriding chronic leg ulcers : TenderWet 24 , which is design ed to support the autolytic degradation process , and Iruxol N ( Santyl ) , an enzymatic treatment cl aim ed to enhance the degradation process . METHOD Patients were r and omly assigned to one of the two treatment groups for three weeks . Wounds were evaluated weekly for the amount of eschar/slough , the area of healthy granulation and the re-epithelialised area . RESULTS During days 1 - 14 slough within the groups was reduced by almost 19 % for TenderWet 24 and by 9 % for Iruxol N , followed by an increase of 26 % and 10 % respectively in granulation tissue . These effects were less accentuated during days 7 - 21 . There was a further 11 % improvement in tissue debridement for the TenderWet 24 group and a relapse ( + 9.1 % ) in the Iruxol N group . CONCLUSION Although TenderWet 24 appeared to be more efficient in a few cases , the general efficacy of the two products appeared to be almost the same as no statistically significant superiority of either product was found UNLABELLED Comparisons of collagenase to other methods of debridement , including wet to dry dressings , have been reported in the literature ; however , studies comparing collagenase to hydrogel have not been reported . OBJECTIVE Time to complete necrotic tissue debridement with collagenase compared to hydrogel in institutionalized adults with pressure ulcers . METHODS R and omization occurred after obtaining informed consent to avoid selection bias . Subjects received daily dressing changes with either hydrogel or collagenase followed by a st and ard semi-occlusive dressing to evaluate time to debridement up to Day 42 . Investigators , who were blinded to r and omization , evaluated weekly wound photographs for necrotic tissue debridement and wound healing parameters using a digital planimetry software package . Nonviable tissue was not cross-hatched in either group . RESULTS Twenty-seven nursing home residents were enrolled over a period of 1 year . According to a Student 's t test , there were no significant differences between groups for age , gender , age of wound , or percentage of nonviable tissue at the time of enrollment ( P = .03 ) . Using a Pearson Chi square analysis , the collagenase group was found to have statistical ( P = .003 ) significance in achieving full debridement by Day 42 . CONCLUSION This study showed statistical significance in favor of collagenase when used to debride nonviable tissue in pressure ulcers . Despite recommendations to cross-hatch eschar , statistical significance was still achieved when wounds were not cross-hatched , indicating clinical utility in setting s without clinician availability for the cross-hatching procedure During burn care the wounds must be repeatedly debrided of adherent and loose debris until the decision is made to surgically excise and graft the wound or to await epithelialization . Though native proteolytic enzymes in the skin or those produced by colonizing bacteria can speed eschar separation , the use of exogenous enzymes for wound debridement may accelerate wound cleaning and healing . Collagenase digests native and denatured collagen in necrotic tissue . This multicenter trial of 79 patients with partial-thickness wounds compared the efficacy of collagenase ointment applied with polymyxin B sulfate/bacitracin powder with the efficacy of st and ard topical antimicrobial therapy ( control ) in which silver sulfadiazine cream ( 1 % ) was used to debride paired burn sites . Patients selected for the study had two noncontiguous , partial-thickness , comparably sized , and anatomically similar burn wounds . Ages of patients ranged from 5 to 60 years ( mean 33 years ) . The total body surface area burned ranged from 2 % to 30 % ( mean 13.6 % ) . Mean burn sizes used for study treatment were 366 cm2 ( 26 to 2310 cm2 ) for col Output:	Results support the use of collagenase for enzymatic debridement in pressure ulcers , diabetic foot ulcers and in conjunction with topical antibiotics for burns .
MS21680	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Virtual reality (VR)-based therapy has emerged as a potentially useful means to treat post-traumatic stress disorder ( PTSD ) , but r and omized studies have been lacking for Service Members from Iraq or Afghanistan . This study documents a small , r and omized , controlled trial of VR- grade d exposure therapy ( VR-GET ) versus treatment as usual ( TAU ) for PTSD in Active Duty military personnel with combat-related PTSD . Success was gauged according to whether treatment result ed in a 30 percent or greater improvement in the PTSD symptom severity as assessed by the Clinician Administered PTSD Scale ( CAPS ) after 10 weeks of treatment . Seven of 10 participants improved by 30 percent or greater while in VR-GET , whereas only 1 of the 9 returning participants in TAU showed similar improvement . This is a clinical ly and statistically significant result ( χ(2 ) = 6.74 , p < 0.01 , relative risk 3.2 ) . Participants in VR-GET improved an average of 35 points on the CAPS , whereas those in TAU averaged a 9-point improvement ( p < 0.05 ) . The results are limited by small size , lack of blinding , a single therapist , and comparison to a relatively uncontrolled usual care condition , but did show VR-GET to be a safe and effective treatment for combat-related PTSD Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field Eleven Vietnam veterans with war-related posttraumatic stress disorder ( PTSD ) were r and omly assigned to 10 sessions of either virtual reality exposure ( VRE ) therapy within a computer-generated virtual Vietnam environment or present-centered therapy ( PCT ) that avoided traumatic content and utilized a problem-solving approach . Participants were assessed at pretreatment , posttreatment , and 6 months posttreatment by an independent assessor blind to treatment condition . Nine participants completed treatment with one dropout per condition . No significant differences emerged between treatments , likely due to insufficient power . Although comparison of mean changes in PTSD symptoms for the VRE and PCT conditions yielded a moderate effect size ( d = 0.56 ) in favor of VRE at 6 months posttreatment , changes in PTSD scores were more variable , and therefore less reliable , within the VRE condition . The utility of VRE with older veterans with PTSD is discussed Numerous reports indicate that the growing incidence of posttraumatic stress disorder ( PTSD ) in returning Operation Enduring Freedom (OEF)/Operation Iraqi Freedom ( OIF ) military personnel is creating a significant health care and economic challenge . These findings have served to motivate research on how to better develop and disseminate evidence -based treatments for PTSD . Virtual reality-delivered exposure therapy for PTSD has been previously used with reports of positive outcomes . The current paper will detail the development and early results from use of the Virtual Iraq/Afghanistan exposure therapy system . The system consists of a series of customizable virtual scenarios design ed to represent relevant Middle Eastern context s for exposure therapy , including a city and desert road convoy environment . The process for gathering user-centered design feedback from returning OEF/OIF military personnel and from a system deployed in Iraq ( as was needed to iteratively evolve the system ) will be discussed , along with a brief summary of results from an open clinical trial using Virtual Iraq with 20 treatment completers , which indicated that 16 no longer met PTSD checklist-military criteria for PTSD after treatment BACKGROUND Virtual reality ( VR ) integrates real-time computer graphics , body-tracking devices , visual displays , and other sensory input devices to immerse a participant in a computer-generated virtual environment that changes in a natural way with head and body motion . VR exposure ( VRE ) is proposed as an alternative to typical imaginal exposure treatment for Vietnam combat veterans with posttraumatic stress disorder ( PTSD ) . METHOD This report presents the results of an open clinical trial using VRE to treat Vietnam combat veterans who have DSM-IV PTSD . In 8 to 16 sessions , 10 male patients were exposed to 2 virtual environments : a virtual Huey helicopter flying over a virtual Vietnam and a clearing surrounded by jungle . RESULTS Clinician-rated PTSD symptoms as measured by the Clinician Administered PTSD Scale , the primary outcome measure , at 6-month follow-up indicated an overall statistically significant reduction from baseline ( p = .0021 ) in symptoms associated with specific reported traumatic experiences . All 8 participants interviewed at the 6-month follow-up reported reductions in PTSD symptoms ranging from 15 % to 67 % . Significant decreases were seen in all 3 symptom clusters ( p < .02 ) . Patient self-reported intrusion symptoms as measured by the Impact of Event Scale were significantly lower ( p < .05 ) at 3 months than at baseline but not at 6 months , although there was a clear trend toward fewer intrusive thoughts and somewhat less avoidance . CONCLUSION Virtual reality exposure therapy holds promise for treating PTSD in Vietnam veterans Posttraumatic stress disorder ( PTSD ) and mild traumatic brain injury ( mTBI ) are signature illnesses of the Iraq and Afghanistan wars , but current diagnostic and therapeutic measures for these conditions are suboptimal . In our study , functional magnetic resonance imaging ( fMRI ) is used to try to differentiate military service members with : PTSD and mTBI , PTSD alone , mTBI alone , and neither PTSD nor mTBI . Those with PTSD are then r and omized to virtual reality exposure therapy or imaginal exposure . fMRI is repeated after treatment and along with the Clinician-Administered PTSD Scale ( CAPS ) and Clinical Global Impression ( CGI ) scores to compare with baseline . Twenty subjects have completed baseline fMRI scans , including four controls and one mTBI only ; of 15 treated for PTSD , eight completed posttreatment scans . Most subjects have been male ( 93 % ) and Caucasian ( 83 % ) , with a mean age of 34 . Significant improvements are evident on fMRI scans , and corroborated by CGI scores , but CAPS scores improvements are modest . In conclusion , CGI scores and fMRI scans indicate significant improvement in PTSD in both treatment arms , though CAPS score improvements are less robust CONTEXT In 2004 , the American Psychiatric Association 's Committee on Research on Psychiatric Treatments appointed a subcommittee to investigate the status of empirical evidence with regard to psychodynamic psychotherapy . OBJECTIVE As a part of this effort , the committee developed a rating scale design ed to assess the quality of r and omized controlled trials ( RCTs ) of psychotherapy . DATA SOURCES A 25-item RCT of Psychotherapy Quality Rating Scale was generated by expert consensus . Interrater reliability , internal consistency , and validity testing were undertaken using 7 trained raters . STUDY SELECTION A PubMed search was conducted to locate all RCTs of psychotherapies identified by their authors as being " psychodynamic " or " psychoanalytic " in origin and implementation . DATA EXTRACTION A total of 69 RCTs were independently rated by 2 raters . DATA SYNTHESIS The scale was found to have good interrater reliability ( total score intraclass correlation = 0.76 ) , internal consistency ( Cronbach alpha = .87 ) , and external validity . CONCLUSIONS This scale establishes a new st and ard for the design and execution of psychotherapy RCTs and provides a systematic empirical method for evaluating the quality of published RCTs Output:	Dropout rates do not seem to be lower than in traditional exposure treatment . Preliminary data suggest that VRET is as efficacious as traditional exposure treatment and can be especially useful in the treatment of patients who are resistant to traditional exposure
MS21681	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Pakistan has high maternal mortality , particularly in the rural areas . The delay in decision making to seek medical care during obstetric emergencies remains a significant factor in maternal mortality . Methods We present results from an experimental study in rural Pakistan . Village clusters were r and omly assigned to intervention and control arms ( 16 clusters each ) . In the intervention clusters , women were provided information on safe motherhood through pictorial booklets and audiocassettes ; traditional birth attendants were trained in clean delivery and recognition of obstetric and newborn complications ; and emergency transportation systems were set up . In eight of the 16 intervention clusters , husb and s also received specially design ed education material s on safe motherhood and family planning . Pre- and post-intervention surveys on selected maternal and neonatal health indicators were conducted in all 32 clusters . A district-wide survey was conducted two years after project completion to measure any residual impact of the interventions . Results Pregnant women in intervention clusters received prenatal care and prophylactic iron therapy more frequently than pregnant women in control clusters . Providing safe motherhood education to husb and s result ed in further improvement of some indicators . There was a small but significant increase in percent of hospital deliveries but no impact on the use of skilled birth attendants . Perinatal mortality reduced significantly in clusters where only wives received information and education in safe motherhood . The survey to assess residual impact showed similar results . Conclusions We conclude that providing safe motherhood education increased the probability of pregnant women having prenatal care and utilization of health services for obstetric complications Abstract s Background Skilled care during and immediately after delivery has been identified as one of the key strategies in reducing maternal mortality . However , recent estimates show that the status of skilled care during delivery remained very low in Ethiopia . Birth preparedness and complication readiness has been implemented as comprehensive strategy to fill this gap . However , its effectiveness in improving skilled care use has n’t been well studied . Objective The objective of this study was to determine the effect of birth preparedness and complication readiness on skilled care use in Southwest Ethiopia . Methods A prospect i ve follow-up study was conducted from September 2012-April 2013 in Southwest Ethiopia among r and omly selected 3472 mothers . Data were collected by using pre-tested interviewer administered question naires and analyzed by using SPSS for windows V.20.0 and STATA 13 . Mixed-effects multilevel logistic regression model was used to look at the relation between birth preparedness and complication readiness plan and skilled care use and identify other determinant factors . Results The status of skilled care use was 17.5 % ( 95 % CI : 16.2 % , 18.8 % ) . Factors affecting skilled care use existed both at the community as well as individual levels . Planning to use skilled care during pregnancy was found to increase actual use significantly ( OR = 2.24 ; 95%CI : 1.60 , 3.15 ) . Place of residence , access to basic emergency obstetric care , maternal education , husb and ’s occupation , wealth quintiles , number of pregnancy , inter-birth interval , knowledge of key danger signs during labor and ANC use were identified as factors affecting skilled care use . Conclusions The status of skilled care use was found to be low in the study area . Birth preparedness and complication readiness had significant effect on skilled care use . Socio-demographic , economic , access to health facility , maternal obstetric factors and antenatal care were identified as determinant factors for skilled care use . Design ing appropriate interventions to improve information , education and communication , antenatal care use , family planning and knowledge of key danger signs are recommended OBJECTIVES To determine the effectiveness of birth plans in increasing use of skilled care at delivery and in the postnatal period among antenatal care ( ANC ) attendees in a rural district with low occupancy of health units for delivery but high antenatal care uptake in northern Tanzania . METHODS Cluster r and omised trial in Ngorongoro district , Arusha region , involving 16 health units ( 8 per arm ) . Nine hundred and five pregnant women at 24 weeks of gestation and above ( 404 in the intervention arm ) were recruited and followed up to at least 1 month postpartum . RESULTS Skilled delivery care uptake was 16.8 % higher in the intervention units than in the control [ 95 % CI 2.6 - 31.0 ; P = 0.02 ] . Postnatal care utilisation in the first month of delivery was higher ( difference in proportions : 30.0 % [ 95 % CI 1.3 - 47.7 ; P < 0.01 ] ) and also initiated earlier ( mean duration 6.6 ± 1.7 days vs. 20.9 ± 4.4 days , P < 0.01 ) in the intervention than in the control arm . Women 's and providers ' reports of care satisfaction ( received or provided ) did not differ greatly between the two arms of the study ( difference in proportion : 12.1 % [ 95 % CI -6.3 - 30.5 ] P = 0.17 and 6.9 % [ 95 % CI -3.2 - 17.1 ] P = 0.15 , respectively ) . CONCLUSION Implementation of birth plans during ANC can increase the uptake of skilled delivery and post delivery care in the study district without negatively affecting women 's and providers ' satisfaction with available ANC services . Birth plans should be considered along with the range of other recommended interventions as a strategy to improve the uptake of maternal health services Background To evaluate a delivery strategy for newborn interventions in rural Bangladesh . Methods A cluster-r and omized controlled trial was conducted in Mirzapur , Bangladesh . Twelve unions were r and omized to intervention or comparison arm . All women of reproductive age were eligible to participate . In the intervention arm , community health workers identified pregnant women ; made two antenatal home visits to promote birth and newborn care preparedness ; made four postnatal home visits to negotiate preventive care practice s and to assess newborns for illness ; and referred sick neonates to a hospital and facilitated compliance . Primary outcome measures were antenatal and immediate newborn care behaviours , knowledge of danger signs , care seeking for neonatal complications , and neonatal mortality . Findings A total of 4616 and 5241 live births were recorded from 9987 and 11153 participants in the intervention and comparison arm , respectively . High coverage of antenatal ( 91 % visited twice ) and postnatal ( 69 % visited on days 0 or 1 ) home visitations was achieved . Indicators of care practice s and knowledge of maternal and neonatal danger signs improved . Adjusted mortality hazard ratio in the intervention arm , compared to the comparison arm , was 1.02 ( 95 % CI : 0.80–1.30 ) at baseline and 0.87 ( 95 % CI : 0.68–1.12 ) at endline . Primary causes of death were birth asphyxia ( 49 % ) and prematurity ( 26 % ) . No adverse events associated with interventions were reported . Conclusion Lack of evidence for mortality impact despite high program coverage and quality assurance of implementation , and improvements in targeted newborn care practice s suggests the intervention did not adequately address risk factors for mortality . The level and cause-structure of neonatal mortality in the local population must be considered in developing interventions . Programs must ensure skilled care during childbirth , including management of birth asphyxia and prematurity , and curative postnatal care during the first two days of life , in addition to essential newborn care and infection prevention and management . Trial Registration Clinical trials.gov Background Fetal and neonatal mortality rates in low-income countries are at least 10-fold greater than in high-income countries . These differences have been related to poor access to and poor quality of obstetric and neonatal care . Methods This trial tested the hypothesis that teams of health care providers , administrators and local residents can address the problem of limited access to quality obstetric and neonatal care and lead to a reduction in perinatal mortality in intervention compared to control locations . In seven geographic areas in five low-income and one middle-income country , most with high perinatal mortality rates and substantial numbers of home deliveries , we performed a cluster r and omized non-masked trial of a package of interventions that included community mobilization focusing on birth planning and hospital transport , community birth attendant training in problem recognition , and facility staff training in the management of obstetric and neonatal emergencies . The primary outcome was perinatal mortality at ≥28 weeks gestation or birth weight ≥1000 g. Results Despite extensive effort in all sites in each of the three intervention areas , no differences emerged in the primary or any secondary outcome between the intervention and control clusters . In both groups , the mean perinatal mortality was 40.1/1,000 births ( P = 0.9996 ) . Neither were there differences between the two groups in outcomes in the last six months of the project , in the year following intervention cessation , nor in the clusters that best implemented the intervention . Conclusions This cluster r and omized comprehensive , large-scale , multi-sector intervention did not result in detectable impact on the proposed outcomes . While this does not negate the importance of these interventions , we expect that achieving improvement in pregnancy outcomes in these setting s will require substantially more obstetric and neonatal care infrastructure than was available at the sites during this trial , and without them provider training and community mobilization will not be sufficient . Our results highlight the critical importance of evaluating outcomes in r and omized trials , as interventions that should be effective may not be . Trial registration Clinical Trials.gov Background Antenatal care provides an important opportunity to improve maternal underst and ing of care during and after pregnancy . Yet , studies suggest that communication is often insufficient . This research examined the effect of a job aids-focused intervention on quality of counseling and maternal underst and ing of care for mothers and newborns . Methods Counseling job aids were developed to support provider communication to pregnant women . Fourteen health facilities were r and omized to control or intervention , where providers were trained to use job aids and provided implementation support . Direct observation of antenatal counseling sessions and patient exit interviews were undertaken to assess quality of counseling and maternal knowledge . Providers were also interviewed regarding their perceptions of the tools . Data were collected before and after the job aids intervention and analyzed using a difference-in-differences analysis to quantify relative changes over time . Results Mean percent of recommended messages provided to pregnant women significantly improved in the intervention arm as compared to the control arm in birth preparedness ( difference-in-differences [ ΔI-C ] = + 17.9 , 95%CI : 6.7,29.1 ) , danger sign recognition ( ΔI-C = + 26.0 , 95%CI : 14.6,37.4 ) , clean delivery ( ΔI-C = + 21.7 , 95%CI : 10.9,32.6 ) , and newborn care ( ΔI-C = + 26.2 , 95%CI : 13.5,38.9 ) . Significant gains were also observed in the mean percent of communication techniques applied ( ΔI-C = + 28.8 , 95%CI : 22.5,35.2 ) and duration ( minutes ) of antenatal consultations ( ΔI-C = + 5.9 , 95%CI : 3.0,8.8 ) . No relative increase was found for messages relating to general prenatal care ( ΔI-C = + 8.2 , 95%CI : -2.6,19.1 ) . The proportion of pregnant women with correct knowledge also significantly improved for birth preparedness ( ΔI-C = + 23.6 , 95%CI : 9.8,37.4 ) , danger sign recognition ( ΔI-C = + 28.7 , 95%CI : 14.2,43.2 ) , and clean delivery ( ΔI-C = + 31.1 , 95%CI : 19.4,42.9 ) . There were no significant changes in maternal knowledge of general prenatal ( ΔI-C = -6.4 , 95%CI : -21.3,8.5 ) or newborn care ( ΔI-C = + 12.7 , 95%CI : -6.1,31.5 ) . Job aids were positively perceived by providers and pregnant women , although time constraints remained for health workers with other clinical responsibilities . Conclusions This study demonstrates that a job aids-focused intervention can be integrated into routine antenatal care with positive outcomes on provider communication and maternal knowledge . Efforts are needed to address time constraints and other communication barriers , including introduction of on-going quality assessment for long-term sustainability BACKGROUND In rural India , most births take place in the home , where high-risk care practice s are common . We developed an intervention of behaviour change management , with a focus on prevention of hypothermia , aim ed at modifying practice s and reducing neonatal mortality . METHODS We did a cluster-r and omised controlled efficacy trial in Shivgarh , a rural area in Uttar Pradesh . 39 village administrative units ( population 104,123 ) were allocated to one of three groups : a control group , which received the usual services of governmental and non-governmental organisations in the area ; an intervention group , which received a preventive package of interventions for essential newborn care ( birth preparedness , clean delivery and cord care , thermal care [ including skin-to-skin care ] , breastfeeding promotion , and danger sign recognition ) ; or another intervention group , which received the package of essential newborn care plus use of a liquid crystal hypothermia indicator ( ThermoSpot ) . In the intervention clusters , community health workers delivered the packages via collective meetings and two antenatal and two postnatal household visitations . Outcome measures included changes in newborn-care practice s and neonatal mortality rate Output:	Although most studies focus on women as the main target group , multi-stakeholder participation with interventions occurring simultaneously at both community and facility level facilitated the impact on seeking skilled care at birth . Increase in formal education for women most likely contributed positively to results .
MS21682	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIMS The study aim ed to highlight any differences between the sequelae of episiorrhaphy performed using the Blair-Donatti and Guilmen-Pontonnier techniques . METHODS A total of 202 pregnant women were recruited in the Obstetrics Ward of Codogno Civic Hospital in 1994 and 1995 . Subjects were r and omly divided into two groups matched for socioeconomic status , age and parity ( group A : Guilmen-Pontonnier suture , group B : Blair-Donatti suture ) . The following parameters were evaluated : pain twenty-four hours , sixty-six hours and one , two and three months after labour , pain during sexual relations , the onset of infection , hematoma , dehiscence of the wound , and lastly the cosmetic results . RESULTS No significant differences were found between the parameters examined in both groups , barring the improved cosmetic result in group Episiotomy is a very common operation but little is known of its short-term or long-term morbidity . A prospect i ve study was design ed to record postpartum perineal discomfort and to investigate the presence and persistence of dyspareunia following episiotomy in 140 primigravidae . A comparison was made between those whose perineal skin was sutured with a subcuticular polyglycolic acid ( ; Dexon ' ) stitch and those sutured with interrupted black silk stitches . Patients sutured with subcuticular ; Dexon ' had significantly less perineal discomfort on the third , fourth , and fifth postpartum days . Patients who had epidural analgesia in labour had significantly more pain during the first five postpartum days irrespective of the suture material used . The timing of first coitus after delivery did not influence the presence or persistence of dyspareunia . Dyspareunia was commoner and lasted longer in patients sutured with ; Dexon ' and it was also commoner in older primigravidae irrespective of the suture technique BACKGROUND Trauma to the perineum is a serious and frequent problem after childbirth , with about 350000 women each year in the UK needing sutures for perineal injury after spontaneous vaginal delivery , and many millions more worldwide . We compared the continuous technique of perineal repair with the interrupted method , and the more rapidly absorbed polyglactin 910 suture material with the st and ard polyglactin 910 material . METHODS 1542 women who had a spontaneous vaginal delivery with a second-degree perineal tear or episiotomy were r and omly allocated to either the continuous ( n=771 ) or interrupted ( 771 ) suturing method , and to either the more rapidly absorbed polyglactin 910 suture material ( 772 ) or st and ard polyglactin 910 material ( 770 ) . Primary outcomes were pain 10 days after delivery and superficial dyspareunia 3 months postpartum . Analysis was by intention to treat . FINDINGS At day 10 , three women had dropped out of the study . Significantly fewer women reported pain at 10 days with the continuous technique than with the interrupted method ( 204/770 [ 26.5 % ] vs 338/769 [ 44.0 % ] , odds ratio 0.47 , 95 % CI 0.38 - 0.58 , p<0.0001 ) . Occurrence of pain did not differ significantly between groups assigned the more rapidly absorbed material or st and ard material ( 256/769 [ 33.3 % ] vs 286/770 [ 37.1 % ] , 0.84 , 0.68 - 1.04 , p=0.10 ) . Women reported no difference in superficial dyspareunia at 3 months for the continuous vs the interrupted method ( 98/581 [ 16.9 % ] vs 102/593 [ 17.2 % ] , 0.98 , 0.72 - 1.33 , p=0.88 ) or the more rapidly absorbed versus st and ard material ( 105/586 [ 17.9 % ] vs 95/588 [ 16.2 % ] , 1.13 , 0.84 - 1.54 , p=0.42 ) . Suture removal was done less with the more rapidly absorbed material than with st and ard suture material ( 22/769 [ 3 % ] vs 98/770 [ 13 % ] , p<0.0001 ) , and with the continuous versus interrupted method ( 24/770 [ 3 % ] vs 96/769 [ 12 % ] , p<0.0001 ) . INTERPRETATION A simple and widely practicable continuous repair technique can prevent one woman in six from having pain at 10 days . Also , the more rapidly absorbed polyglactin 910 material obviates need for suture removal up to 3 months postpartum for one in ten women sutured Purpose To compare different repair techniques and different suture material s for episiotomy . Methods 160 women having vertex delivery with right-mediolateral episiotomy were r and omly allocated to four groups . In the groups where continuos technique was performed , vaginal mucosa , perineal muscles and the skin were sutured continuously . In the groups of interrupted technique , vaginal mucosa was sutured with continuous sutures , then muscle layers and skin were closed by interrupted sutures . Two different types of synthetic absorbed suture material were used : monofilament type is in form of polyglycolide-co-caprolactone and multifilament one is polyglactin 910-Rapide . Perineal pain during different activities on the first and tenth day postpartum and also during sexual intercourse 6 weeks after the delivery was question ed by visual analogous scale ( VAS ) . Furthermore , repair time , amount of suture and episiotomy complications were investigated in each groups . Results On the first day after delivery , the perineal pain scores , the repair time , the amount of suture were statistically less in the continuous technique groups . The differences between the pain at tenth day and during sexual intercourse 6 weeks after the delivery were statistically same . Conclusions The continuous suturing techniques for episiotomy closure , compared to interrupted methods , are associated with less short-term pain , are quicker and also need less suture material Objective To assess the long term implication s of four alternative approaches to postpartum perineal repair . Objective To compare the effect of two methods of perineal management used during spontaneous vaginal delivery on the prevalence of perineal pain reported at 10 days after birth The aim was to compare healing and perineal pain with the use of continuous and interrupted suture techniques in women after normal delivery . A r and omized controlled trial was carried out at a hospital birth center in Itapecirica da Serra , Sao Paulo , Brazil . A total of 61 women participated with episiotomy or second degree perineal tear , allocated in two groups according to the continuous ( n=31 ) or interrupted ( n=30 ) suture techniques . The main outcomes evaluated were edema , ecchymosis , hyperemia , secretion , dehiscence , fibrosis , frequency and degree of pain ( evaluated by numerical scale from 1 to 10 ) . Data were collected during hospitalization and after discharge ( four and 41 days after birth ) . Healing occurred by first intention in 100 % of cases in both suture techniques . There were no statistically significant differences for the occurrence of morbidities , except for perineal pain due to palpation at four days after delivery , which was more frequent among women with interrupted suture OBJECTIVE Our purpose was to compare consequences for women of receiving versus not receiving median episiotomy early and 3 months post partum on the outcomes perineal pain , urinary and pelvic floor functioning by electromyography , and sexual functioning and to analyze the relationship between episiotomy and third- and fourth-degree tears . STUDY DESIGN A secondary cohort analysis was performed of participants within a r and omized clinical trial , analyzed by type of perineal trauma and pain , pelvic floor , and sexual consequences of such trauma , while controlling for trial arm . The study was conducted in three university or community hospitals ; 356 primiparous and 341 multiparous women were studied . RESULTS Early and 3-month-postpartum perineal pain was least for women who gave birth with an intact perineum . Spontaneous perineal tears were less painful than episiotomy . Sexual functioning was best for women with an intact perineum or perineal tears . Postpartum urinary and pelvic floor symptoms were similar in all perineal groups . At 3 months post partum those delivered with an intact perineum had the strongest pelvic floor musculature , those with episiotomy the weakest . Among primiparous women third- and fourth-degree tears were associated with median episiotomy ( 46/47 ) . After forceps births were removed and 21 other variables potentially associated within such tears were controlled for , episiotomy was strongly associated with third- and fourth-degree tears ( odds ratio + 22.08 , 95 % confidence interval 2.84 to 171.53 ) . Physicians using episiotomy at high rates also used other procedures , including cesarean section , more frequently . CONCLUSION Perineal and pelvic floor morbidity was greatest among women receiving median episiotomy versus those remaining intact or sustaining spontaneous perineal tears . Median episiotomy was causally related to third- and fourth-degree tears . Those using episiotomy at the highest rates were more likely use other interventions as well . Episiotomy use should be restricted to specified fetal-maternal indications typic abnormalities in early onset severe growth retardation ( Fisk et al. 1989 ; Nicolaides et al. 1989 ; Sipes et al. 1991 ) . However , since there is an overlap in mean corpuscular volume between triploid and chromosomally normal growth-retarded fetuses ( Nicolaides et al. 1989 ) it is necessary that the diagnosis is confirmed by cytogenetic analysis which usually takes 7 - 10 days . Using flow cytometry and st and ard DNA quantification techniques , which are now widely used in the clinical management of haematological and other neoplasias , it is possible to diagnose fetal triploidy from fetal blood , within l h of sampling Summary . Three methods of episiotomy repair were r and omly assigned after 900 consecutive deliveries . The three procedures were : ( 1 ) continuous No. 00‐plain catgut in the vagina ; No. 00‐plain catgut interrupted stiches in the perineal muscles and fascia , and No. 00‐nylon interrupted stiches in the skin . ( 2 ) The same technique as in ( l ) , but with No. 0‐polyglycolic acid ( Dexon ) in all layers . ( 3 ) The suture material as in ( 2 ) , but used with a subcuticular technique . The women treated with method 3 reported statistically significant less pain and disabilities in the early puerperium . Three months after delivery 262 women ( 33 % ) still had perineal complaints which could be directly related to the episiotomy in 25 % ( 8 % of total number ) . The group treated with method 3 had the best long‐term results and we conclude that the subcuticular technique using polyglycolic acid should be the method of choice One thous and women were allocated at r and om to one of two perineal management policies , both intended to minimise trauma during spontaneous vaginal delivery . In one the aim was to restrict episiotomy to fetal indications ; in the other the operation was to be used more liberally to prevent perineal tears . The result ant episiotomy rates were 10 % and 51 % respectively . An intact perineum was more common among those allocated to the restrictive policy . This group experienced more perineal and labial tears , however , and included four of the five cases of severe trauma . There were no significant differences between the two groups either in neonatal state or in maternal pain and urinary symptoms 10 days and three months post partum . Women allocated to the restrictive policy were more likely to have resumed sexual intercourse within a month after delivery . These findings provide little support either for liberal use of episiotomy or for cl aims that reduced use of the operation decreases postpartum morbidity We set out to compare a policy of two-layered postpartum perineal repair leaving the skin unsutured with a policy of three-layered repair , which involved skin closure . Parturients who sustained a second-degree tear or an episiotomy in four Nigerian centers were r and omised to have either a two-layered repair ( 417 women ) or a three-layered repair ( 406 women ) . Fewer women in the two-layered group reported perineal pain at 48 hours ( 57 % vs. 65 % , relative risk [ RR ] 0.87 , 95 % confidence interval [ CI ] 0.78 - 0.97 ) and 14 days postpartum ( 22 % vs. 28 % , RR 0.77 , CI 0.61 - 0.98 ) . The two-layered repair was also associated with reduced risk of suture removal ( 6 % vs. 10 % , RR 0.62 , CI 0.39 - 0.99 ) , and less superficial dyspareunia at 3 months ( 6 % vs. 12 % , RR 0.52 , CI 0.33 - 0.81 ) . The rates of wound healing were similar between the two groups . Leaving the skin unsutured during postpartum perineal repair reduces perineal pain and dyspareunia Commonly used suture material s and techniques for perineal repair following vaginal delivery were compared in a r and omized controlled trial involving 1574 women . Three comparisons were made using a modified factorial design . In the comparison of teflon‐coated polyglycolic acid ( D Output:	AUTHORS ' CONCLUSIONS The continuous suturing techniques for perineal closure , compared with interrupted methods , are associated with less short-term pain , need for analgesia and suture removal .
MS21683	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES The aim of these two studies was to evaluate the effectiveness of the Mindful Self-Compassion ( MSC ) program , an 8-week workshop design ed to train people to be more self-compassionate . METHODS Study 1 was a pilot study that examined change scores in self-compassion , mindfulness , and various wellbeing outcomes among community adults ( N = 21 ; mean [ M ] age = 51.26 , 95 % female ) . Study 2 was a r and omized controlled trial that compared a treatment group ( N = 25 ; M age = 51.21 ; 78 % female ) with a waitlist control group ( N = 27 ; M age = 49.11 ; 82 % female ) . RESULTS Study 1 found significant pre/post gains in self-compassion , mindfulness , and various wellbeing outcomes . Study 2 found that compared with the control group , intervention participants reported significantly larger increases in self-compassion , mindfulness , and wellbeing . Gains were maintained at 6-month and 1-year follow-ups . CONCLUSIONS The MSC program appears to be effective at enhancing self-compassion , mindfulness , and wellbeing The ability to accurately infer others ' mental states from facial expressions is important for optimal social functioning and is fundamentally impaired in social cognitive disorders such as autism . While pharmacologic interventions have shown promise for enhancing empathic accuracy , little is known about the effects of behavioral interventions on empathic accuracy and related brain activity . This study employed a r and omized , controlled and longitudinal design to investigate the effect of a secularized analytical compassion meditation program , cognitive-based compassion training ( CBCT ) , on empathic accuracy . Twenty-one healthy participants received functional MRI scans while completing an empathic accuracy task , the Reading the Mind in the Eyes Test ( RMET ) , both prior to and after completion of either CBCT or a health discussion control group . Upon completion of the study interventions , participants r and omized to CBCT and were significantly more likely than control subjects to have increased scores on the RMET and increased neural activity in the inferior frontal gyrus ( IFG ) and dorsomedial prefrontal cortex ( dmPFC ) . Moreover , changes in dmPFC and IFG activity from baseline to the post-intervention assessment were associated with changes in empathic accuracy . These findings suggest that CBCT may hold promise as a behavioral intervention for enhancing empathic accuracy and the neurobiology supporting it Recent empirical evidence supports the importance of adequate r and omization in controlled trials . Trials with inadequate allocation concealment have been associated with larger treatment effects compared with trials in which authors reported adequate allocation concealment . While that provides empirical evidence of bias being interjected into trials , trial investigators rarely document the sensitive details of subverting the intended purpose of r and omization . This article relates anonymous accounts run the gamut from simple to intricate operations , from transillumination of envelopes to search ing for code in the office files of the principal investigator . They indicate that deciphering is something more frequent than a rate occurrence . These accounts prompt some method ological recommendations to help prevent deciphering . R and omized controlled trials appear to annoy human nature -- if properly conducted , indeed they should Conditional goal setting ( CGS , the tendency to regard high order goals such as happiness , as conditional upon the achievement of lower order goals ) is observed in individuals with depression and recent research has suggested a link between levels of dispositional mindfulness and conditional goal setting in depressed patients . Since interventions which aim to increase mindfulness through training in meditation are used with patients suffering from depression it is of interest to examine whether such interventions might alter CGS . Study 1 examined the correlation between changes in dispositional mindfulness and changes in CGS over a 3 - 4 month period in patients participating in a pilot r and omised controlled trial of Mindfulness-Based Cognitive Therapy ( MBCT ) . Results indicated that increases in dispositional mindfulness were significantly associated with decreases in CGS , although this effect could not be attributed specifically to the group who had received training in meditation . Study 2 explored the impact of brief periods of either breathing or loving kindness meditation on CGS in 55 healthy participants . Contrary to expectation , a brief period of meditation increased CGS . Further analyses indicated that this effect was restricted to participants low in goal re-engagement ability who were allocated to loving kindness meditation . Longer term changes in dispositional mindfulness are associated with reductions in CGS in patients with depressed mood . However initial reactions to meditation , and in particular loving kindness meditation , may be counterintuitive and further research is required in order to determine the relationship between initial reactions and longer-term benefits of meditation practice B. L. Fredrickson 's ( 1998 , 2001 ) broaden- and -build theory of positive emotions asserts that people 's daily experiences of positive emotions compound over time to build a variety of consequential personal re sources . The authors tested this build hypothesis in a field experiment with working adults ( n = 139 ) , half of whom were r and omly-assigned to begin a practice of loving-kindness meditation . Results showed that this meditation practice produced increases over time in daily experiences of positive emotions , which , in turn , produced increases in a wide range of personal re sources ( e.g. , increased mindfulness , purpose in life , social support , decreased illness symptoms ) . In turn , these increments in personal re sources predicted increased life satisfaction and reduced depressive symptoms . Discussion centers on how positive emotions are the mechanism of change for the type of mind-training practice studied here and how loving-kindness meditation is an intervention strategy that produces positive emotions in a way that outpaces the hedonic treadmill effect Meditation practice s may impact physiological pathways that are modulated by stress and relevant to disease . While much attention has been paid to meditation practice s that emphasize calming the mind , improving focused attention , or developing mindfulness , less is known about meditation practice s that foster compassion . Accordingly , the current study examined the effect of compassion meditation on innate immune , neuroendocrine and behavioral responses to psychosocial stress and evaluated the degree to which engagement in meditation practice influenced stress reactivity . Sixty-one healthy adults were r and omized to 6 weeks of training in compassion meditation ( n=33 ) or participation in a health discussion control group ( n=28 ) followed by exposure to a st and ardized laboratory stressor ( Trier social stress test [ TSST ] ) . Physiologic and behavioral responses to the TSST were determined by repeated assessment s of plasma concentrations of interleukin (IL)-6 and cortisol as well as total distress scores on the Profile of Mood States ( POMS ) . No main effect of group assignment on TSST responses was found for IL-6 , cortisol or POMS scores . However , within the meditation group , increased meditation practice was correlated with decreased TSST-induced IL-6 ( r(p)=-0.46 , p=0.008 ) and POMS distress scores ( r(p)=-0.43 , p=0.014 ) . Moreover , individuals with meditation practice times above the median exhibited lower TSST-induced IL-6 and POMS distress scores compared to individuals below the median , who did not differ from controls . These data suggest that engagement in compassion meditation may reduce stress-induced immune and behavioral responses , although future studies are required to determine whether individuals who engage in compassion meditation techniques are more likely to exhibit reduced stress reactivity Decentering has been proposed as a potential mechanism of mindfulness-based interventions but has received limited empirical examination to date in experimental studies comparing mindfulness meditation to active comparison conditions . In the present study , we compared the immediate effects of mindful breathing ( MB ) to two alternative stress-management techniques : progressive muscle relaxation ( PMR ) and loving-kindness meditation ( LKM ) to test whether decentering is unique to mindfulness meditation or common across approaches . Novice meditators ( 190 female undergraduates ) were r and omly assigned to complete one of three 15-min stress-management exercises ( MB , PMR , or LKM ) presented by audio recording . Immediately after the exercise , participants completed measures of decentering , frequency of repetitive thoughts during the exercise , and degree of negative reaction to thoughts . As predicted , participants in the MB condition reported greater decentering relative to the other two conditions . The association between frequency of repetitive thought and negative reactions to thoughts was relatively weaker in the MB condition than in the PMR and LKM conditions , in which these two variables were strongly and positively correlated . Consistent with the construct of decentering , the relative independence between these two variables in the MB condition suggests that mindful breathing may help to reduce reactivity to repetitive thoughts . Taken together , results help to provide further evidence of decentering as a potential mechanism that distinguishes mindfulness practice from other credible stress-management approaches Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more This pilot study examined loving-kindness meditation ( LKM ) with 18 participants with schizophrenia-spectrum disorders and significant negative symptoms . Findings indicate that the intervention was feasible and associated with decreased negative symptoms and increased positive emotions and psychological recovery Most studies of meditation have focused on " actual affect " ( how people actually feel ) . We predict that meditation may even more significantly alter " ideal affect " ( how people ideally want to feel ) . As predicted , meditators ideally wanted to feel calm more and excited less than nonmeditators , but the groups did not differ in their actual experience of calm or excited states ( Study 1 ) . We ruled out self- selection and nonspecific effects by r and omly assigning participants to meditation classes , an improvisational theater class , or a no class control ( Study 2 ) . After eight weeks , meditators valued calm more but did not differ in their actual experience of calm compared with the other groups . There were no differences in ideal or actual excitement , suggesting that meditation selectively increases the value placed on calm . These findings were not due to expectancy effects ( Study 3 ) . We discuss the implication s of these findings for underst and ing how meditation alters affective life Objective To evaluate the reliability of risk of bias assessment s based on published trial reports , for determining trial inclusion in meta-analyses . Design Reliability evaluation of risk of bias assessment s. Data sources 13 published individual participant data ( IPD ) meta-analyses in cancer were used to source 95 r and omised controlled trials . Review methods Risk of bias was assessed using the Cochrane risk of bias tool ( RevMan5.1 ) and accompanying guidance . Assessment s were made for individual risk of bias domains and overall for each trial , using information from either trial reports alone or trial reports with additional information collected for IPD meta-analyses . Percentage agreements were calculated for individual domains and overall ( < 66%=low , ≥66%=fair , ≥90%=good ) . The two approaches were considered similarly reliable only when agreement was good . Results Percentage agreement between the two methods for sequence generation and incomplete outcome data was fair ( 69.5 % ( 95 % confidence interval 60.2 % to 78.7 % ) and 80.0 % ( 72.0 % to 88.0 % ) , respectively ) . However , percentage agreement was low for allocation concealment , selective outcome reporting , and overall risk of bias ( 48.4 % ( 38.4 % to 58.5 % ) , 42.1 % ( 32.2 % to 52.0 % ) , and 54.7 % ( 44.7 % to 64.7 % ) , respectively ) . Supplementary information reduced the proportion of unclear assessment s for all individual domains , consequently increasing the number of trials assessed as low risk of bias ( and therefore available for inclusion in meta-analyses ) from 23 ( 23 % ) based on publications alone to 66 ( 66 % ) based on publications with additional information . Conclusions Using cancer trial publications alone to assess risk of bias could be unreliable ; thus , review ers should be cautious about using them as a basis for trial inclusion , particularly for those trials assessed as unclear risk . Supplementary information from trialists should be sought to enable appropriate assessment s and potentially reduce or overcome some risks of bias . Furthermore , guidance should ensure clarity on what constitutes risk of bias , particularly for the more subjective domains BACKGROUND A growing body of research shows that mindfulness meditation can alter neural , behavioral and biochemical processes . However , the mechanisms responsible for such clinical ly relevant effects remain elusive . METHODS Here we explored the impact of a day of intensive practice of mindfulness meditation in experienced subjects ( n=19 ) on the expression of circadian , chromatin modulatory and inflammatory genes in peripheral blood mononuclear cells ( P BMC ) . In parallel , we analyzed a control group of subjects with no meditation experience who engaged in leisure activities in the same environment ( n=21 ) . P BMC from all participants were obtained before ( t1 ) and after ( t2 ) the intervention ( t2-t1=8h ) and gene expression was analyzed using custom pathway focused quantitative-real time PCR assays . Both groups were also presented with the Trier Social Stress Test ( TSST ) . RESULTS Core clock gene expression at baseline ( t1 ) was similar between groups and their rhythmicity was not influenced in meditators by the intensive day of practice . Similarly , we found that all the epigenetic regulatory enzymes and inflammatory genes analyzed exhibited similar basal expression levels in the two groups . In contrast , after the brief intervention we detected reduced expression of histone deacetylase genes ( HDAC 2 , 3 and 9 ) , alterations in global modification of histones ( H4ac ; H3K4me3 ) and decreased expression of pro-inflammatory genes ( RIPK2 and COX2 ) in meditators compared with controls . We found that the expression of RIPK2 and HDAC2 genes was associated with a faster cortisol recovery to the TS Output:	Exposure to KBM may initially be challenging for some people . RESULTS were inconclusive for some outcomes , in particular against active controls . KBM showed evidence of benefits for the health of individuals and communities through its effects on well-being and social interaction .
MS21684	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This prospect i ve study examined the relation of neonatal sucking to later feeding , postnatal growth , maternal postpartum depression , and feeding practice s. Healthy infants of at least 37 weeks gestational age were recruited . At 1 week of age , a strain-gage device was attached to the infant 's cheeks during sucking to identify sucking efficiency . Two-hundred and two infants ( 100 males , 102 females ; mean age 39.6 weeks , SD 1.1 weeks ) with efficient sucking and 207 ( 101 males , 106 females ; mean gestational age 39.4 weeks , SD 1.2 weeks ) with inefficient sucking were identified . Growth was measured at 2 , 6 , 10 , and 14 months . Mothers completed a feeding question naire and the Edinburgh Postnatal Depression Scale at the same testing points . While 18 infants ( 5 % ) showed a downward shift in growth , their clinical picture did not present as non-organic failure to thrive ( NFTT ) . Inefficient neonatal sucking did not predict postnatal growth , later feeding difficulties , nor maternal feeding practice s , but concurrent inefficient feeding did . Maternal depression did not affect feeding practice s , infant feeding abilities , nor growth , suggesting that the importance of maternal postpartum depression in association with feeding may be less than previously assumed . The term NFTT , therefore , merits reexamination and a more focused definition BACKGROUND Although much research has focused on identifying factors that influence breastfeeding initiation and duration , many high-risk factors are nonmodifiable demographic variables . Predisposing factors for low breastfeeding duration rates that are amenable to supportive interventions should be identified . The purpose of this study was to assess the effect of maternal confidence ( breastfeeding self-efficacy ) on breastfeeding duration . METHOD A prospect i ve survey was conducted with 300 women in the last trimester of pregnancy recruited from the antenatal clinic of a large metropolitan hospital in Brisbane , Australia . Telephone interviews were conducted at 1 week and 4 months postpartum to assess infant feeding methods and breastfeeding confidence using the Breastfeeding Self-Efficacy Scale . RESULTS Although 92 percent of participants initiated breastfeeding , by 4 months postpartum almost 40 percent discontinued and only 28.6 percent were breastfeeding exclusively ; the most common reason for discontinuation was insufficient milk supply . Antenatal and 1-week Breastfeeding Self-Efficacy Scale scores were significantly related to breastfeeding outcomes at 1 week and 4 months . Mothers with high breastfeeding self-efficacy were significantly more likely to be breastfeeding , and doing so exclusively , at 1 week and 4 months postpartum than mothers with low breastfeeding self-efficacy . CONCLUSIONS Maternal breastfeeding self-efficacy is a significant predictor of breastfeeding duration and level . Integrating self-efficacy enhancing strategies may improve the quality of healthcare that healthcare professionals deliver and may increase a new mother 's confidence in her ability to breastfeed , and to persevere if she does encounter difficulties One method used to determine utilization rates of cervical screening is women 's self-report . Few studies have assessed the accuracy of this measure -- none has been conducted in Australia -- although there are a number of reasons for suspecting its validity . This study examined and quantified the accuracy of self-report of Pap smear use among a r and omly selected sample of women from an Australian community . Accuracy of Pap smear utilization self-report within a three-year period was assessed by comparison with pathology records . Results indicated that almost half of the women who have not had Pap smears within three years will be missed by a self-report measure of utilization . Some implication s for the measurement and use of self-report data are discussed One hundred and forty-two women at six weeks postpartum were asked to complete Cox 's Edinburgh Postnatal Depression Scale . Thirty-eight scored positively for depression and 28 of these were followed up by a psychiatrist . Twenty-eight controls were r and omly selected from those who scored negatively . Numerous variables were considered , including the type of labour , whether the mother was breastfeeding or not , and the presence or absence of a psychiatric history . In addition the depressed group completed the Eysenck Personality Inventory . A past psychiatric history was found to be a very significant risk factor and there is a definite association between postnatal depression and delivery by forceps , vacuum or caesarian section . Maternal age and breastfeeding were not found to be of aetiological significance BACKGROUND Postnatal depression is a major public health problem . The aim of this study is to vali date the use of the Edinburgh Postnatal Depression Scale ( EPDS ) in the early postpartum , and to identify the markers for risk of postnatal depression . METHODS 815 women filled out an EPDS and general information question naire between the third and the fifth day postpartum . The women with an EPDS score of > 8 and a r and omized control group from those with scores of < 8 were contacted 8 weeks postpartum . 363 women therefore had a structured diagnostic interview by telephone at 8 weeks postpartum ( MINI-DSM-IV ) , without knowledge of their EPDS scores , to screen for a major or minor depressive episode . RESULTS The sensitivity of EPDS was measured as 0.82 [ 0.78 - 0.86 ] , with a positivity threshold of 9.5/30 . For an estimated prevalence for all depressive episodes of 16.1 % , the positive predictive value of EPDS was measured as 42.8 % [ 39.1 - 46.5 % ] . Multivariate risk analysis using logistical regression identified the following as risk markers for postnatal depression : previous history of depression ( postnatal or other ) , unemployment , premature delivery or stopping breast-feeding in the first month for non-medical reasons . CONCLUSION The use of EPDS between the third and fifth day postpartum is valid . An EPDS score of > 10 should be completed by a clinical assessment and suitable management . The risk markers identified here are clinical indices that can be used for first-line early screening by non-psychiatric health workers OBJECTIVE Breastfeeding rates fall short of goals set in Healthy People 2010 and other national recommendations . The current , national breastfeeding continuation rate of 29 % at 6 months lags behind the Healthy People 2010 goal of 50 % . The objective of this study was to evaluate associations between breastfeeding discontinuation at 2 and 12 weeks postpartum and clinician support , maternal physical and mental health status , workplace issues , and other factors amenable to intervention . METHODS A prospect i ve cohort study was conducted of low-risk mothers and infants who were in a health maintenance organization and enrolled in a r and omized , controlled trial of home visits . Mothers were interviewed in person at 1 to 2 days postpartum and by telephone at 2 and 12 weeks . Logistic regression modeling was performed to assess the independent effects of the predictors of interest , adjusting for sociodemographic and other confounding variables . RESULTS Of the 1163 mother-newborn pairs in the cohort , 1007 ( 87 % ) initiated breastfeeding , 872 ( 75 % ) were breastfeeding at the 2-week interview , and 646 ( 55 % ) were breastfeeding at the 12-week interview . In the final multivariate models , breastfeeding discontinuation at 2 weeks was associated with lack of confidence in ability to breastfeed at the 1- to 2-day interview ( odds ratio [ OR ] : 2.8 ; 95 % confidence interval [ CI ] : 1.02 - 7.6 ) , early breastfeeding problems ( OR : 1.5 ; 95 % CI : 1.1 - 1.97 ) , Asian race/ethnicity ( OR : 2.6 ; 95 % CI : 1.1 - 5.7 ) , and lower maternal education ( OR : 1.5 ; 95 % CI : 1.2 - 1.9 ) . Mothers were much less likely to discontinue breastfeeding at 12 weeks postpartum if they reported ( during the 12-week interview ) having received encouragement from their clinician to breastfeed ( OR : 0.6 ; 95 % CI : 0.4 - 0.8 ) . Breastfeeding discontinuation at 12 weeks was also associated with demographic factors and maternal depressive symptoms ( OR : 1.18 ; 95 % CI : 1.01 - 1.37 ) and returning to work or school by 12 weeks postpartum ( OR : 2.4 ; 95 % CI : 1.8 - 3.3 ) . CONCLUSIONS Our results indicate that support from clinicians and maternal depressive symptoms are associated with breastfeeding duration . Attention to these issues may help to promote breastfeeding continuation among mothers who initiate . Policies to enhance scheduling flexibility and privacy for breastfeeding mothers at work or school may also be important , given the elevated risk of discontinuation associated with return to work or school STUDY OBJECTIVE --Retrospective infant feeding data are important to the study of child and adult health patterns . The accuracy of maternal recall of past infant feeding events was examined and specifically the infant 's age when breast feeding was stopped and formula feeding and solid foods were introduced . DESIGN AND SETTING --The sample consisted of Bedouin Arab women ( n = 318 ) living in the Negev in Israel who were a part of a larger cohort participating in a prospect i ve study of infant health and who were delivered of their infants between July 1 and December 15 , 1981 . Data from interviews conducted 12 and 18 months postpartum were compared to the st and ard data collected six months postpartum . MAIN RESULTS --As length of recall increased there was a small increase in the mean difference , and its st and ard deviation , between the st and ard and recalled age when breast feeding was stopped and formula feeding and solid foods were started . Recall on formula feeding was less accurate than recall on solid foods and breast feeding . In particular , among those 61 % reporting formula use at the six month interview , 51 % did not recall introducing formula when interviewed at 18 months . The odds ratio ( 95 % CI ) of stunting versus normal length for age for formula fed versus breast fed infants based on recall data ( OR = 2.07 ; 95 % CI 0.82 - 5.22 ) differed only slightly from those based on the st and ard data ( OR = 2.21 ; 95 % CI 0.77 - 6.37 ) . The accuracy of a mother 's recall varied with her child 's nutritional status at the time of the interview , but not with other sociodemographic , infant , or interviewer characteristics . CONCLUSIONS --Retrospective infant feeding data based on maternal recall of events up to 18 months in the past can be used with confidence in epidemiological studies . However , data on formula feeding may not be as accurate as data on breast feeding and solid food feeding , and accuracy may decrease as length of recall increases Despite well-documented health benefits of breastfeeding for mothers and babies , most women discontinue breastfeeding before the recommended 12 months to 2 years . The purpose of this study was to assess the effect of modifiable antenatal variables on breastfeeding outcomes . A prospect i ve , longitudinal study was conducted with 300 pregnant , Australian women . Question naires containing variables of interest were administered to women during their last trimester ; infant feeding method was assessed at 1 week and 4 months postpartum . Intended breastfeeding duration and breastfeeding self-efficacy were identified as the most significant modifiable variables predictive of breastfeeding outcomes . Mothers who intended to breastfeed for < 6 months were 2.4 times as likely to have discontinued breastfeeding at 4 months compared to those who intended to breastfeed for > 12 months ( 35.7 % vs 87.5 % ) . Similarly , mothers with high breastfeeding self-efficacy were more likely to be breastfeeding compared to mothers with low self-efficacy ( 79.3 % vs 50.0 % ) . J Hum Lact . 20(1):30 - 38 Hormonal factors have been suggested as a cause of post-natal depression , but suckling frequency which is the major influence on hormone levels post-partum has not been considered in previous studies . Eighty-nine women who had taken part in a prospect i ve study of post-natal depression were asked about their feeding patterns 18 months after childbirth . Half the mothers who were breast feeding introduced solids or artificial milk feeds before 12 weeks and were likely to have lowered prolactin levels and increased ovarian follicular activity . Mothers who totally breastfed their babies for at least 12 weeks or who were on the pill , had a higher incidence of post-natal depression than those who were not on the pill or who partially breastfed . Among the 62 women who attempted breast feeding those most likely to have normal levels of endogenous hormones were those least likely to have depressive symptoms Purpose To examine patterns of exclusive breastfeeding , combination feeding , and exclusive bottle-feeding among a sample of women identified at 2–4 weeks postpartum with positive PPD symptoms . Study Design and Methods The sample included 122 women who were part of a larger study testing an intervention for promoting maternal-infant interaction among women with elevated PPD symptoms . Data were collected during three postpartum home visits . Demographic and feeding pattern data were described . Variables related to and predictors of feeding pattern were analyzed . The sample was compared to a r and om sample of postpartum women in New Engl and . Results Severity of depression was not significantly related to breastfeeding . Older maternal age , living with a partner , and higher income were positively related to breastfeeding . Comp Output:	The results from this review suggest that women with depressive symptomatology in the early postpartum period may be at increased risk for negative infant-feeding outcomes including decreased breastfeeding duration , increased breastfeeding difficulties , and decreased levels of breastfeeding self-efficacy . There is also beginning evidence to suggest that depressed women may be less likely to initiate breastfeeding and do so exclusively . Depressive symptomatology in the postpartum period negatively influences infant-feeding outcomes .
MS21685	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND This study compared the induction regimens doxorubicin , cyclophosphamide and etoposide ( ACE ) with doxorubicin , cyclophosphamide , vincristine , bleomycin and prednisone ( ACVBP ) before high-dose therapy ( HDT ) followed by autologous stem-cell transplantation ( ASCT ) for patients with poor-risk diffuse large B-cell lymphoma ( DLBCL ) . A second r and omisation compared rituximab with observation post-ASCT . MATERIAL S AND METHODS Four hundred and seventy-six patients < 60 years old with newly diagnosed CD20 + DLBCL were r and omised to induction with ACE or ACVBP . Three hundred and thirty responders received HDT followed by ASCT . After ASCT , 269 patients were re-r and omised to receive either maintenance rituximab or observation alone . R and omisation was stratified by the quality of response to ASCT . The primary end point of this study was event-free survival ( EFS ) . RESULTS At a median of 4 years ' follow-up from the second r and omisation , there was a trend ( P = 0.1 ) towards increased EFS for patients who received rituximab compared with observation . CONCLUSION The type of induction therapy ( ACVBP or ACE ) did not significantly affect overall survival at a median 51 months ' follow-up Background Patients with diffuse large B-cell lymphoma ( DLBCL ) with an International Prognostic Index ( IPI ) ≥3 are at higher risk for relapse after a complete response ( CR ) to first-line rituximab-based chemotherapy ( R-chemo ) . Everolimus has single-agent activity in lymphoma . PILLAR-2 aim ed to improve disease-free survival ( DFS ) with 1 year of adjuvant everolimus . Patients and methods Patients with high-risk ( IPI ≥3 ) DLBCL and a positron emission tomography/computed tomography-confirmed CR to first-line R-chemo were r and omized to 1 year of everolimus 10 mg/day or placebo . The primary end point was DFS ; secondary end points were overall survival , lymphoma-specific survival , and safety . Results Between August 2009 and December 2013 , 742 patients were r and omized to everolimus ( n = 372 ) or placebo ( n = 370 ) . Median follow-up was 50.4 months ( range 24.0 - 76.9 ) . Overall , 47 % of patients were ≥65 years , 50 % were male , and 42 % had an IPI of 4 or 5 . 48 % and 67 % completed everolimus and placebo , respectively . Primary reasons for everolimus discontinuation versus placebo were adverse events ( AEs ; 30 % versus 12 % ) and relapsed disease ( 6 % versus 13 % ) . Everolimus did not significantly improve DFS compared with placebo ( hazard ratio 0.92 ; 95 % CI 0.69 - 1.22 ; P = 0.276 ) . Two-year DFS rate was 77.8 % ( 95 % CI 72.7 - 82.1 ) with everolimus and 77.0 % ( 95 % CI 72.1 - 81.1 ) with placebo . Common grade 3/4 AEs with everolimus were neutropenia , stomatitis , and decreased CD4 lymphocytes . Conclusions Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR . Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained . Clinical Trials.gov NCT00790036 Purpose The st and ard treatment of patients with diffuse large B-cell lymphoma ( DLBCL ) is rituximab in combination with cyclophosphamide , doxorubicin , vincristine , and prednisone ( R-CHOP ) . Lenalidomide , an immunomodulatory agent , has shown activity in DLBCL . This r and omized phase III trial compared lenalidomide as maintenance therapy with placebo in elderly patients with DLBCL who achieved a complete response ( CR ) or partial response ( PR ) to R-CHOP induction . Methods Patients with previously untreated DLBCL or other aggressive B-cell lymphoma were 60 to 80 years old , had CR or PR after six or eight cycles of R-CHOP , and were r and omly assigned to lenalidomide maintenance 25 mg/d or placebo for 21 days of every 28-day cycle for 24 months . The primary end point was progression-free survival ( PFS ) . Results A total of 650 patients were r and omly assigned . At the time of the primary analysis ( December 2015 ) , with a median follow-up of 39 months from r and om assignment , median PFS was not reached for lenalidomide maintenance versus 58.9 months for placebo ( hazard ratio , 0.708 ; 95 % CI , 0.537 to 0.933 ; P = .01 ) . The result was consistent among analyzed subgroups ( eg , male v female , age-adjusted International Prognostic Index 0 or 1 v 2 or 3 , age younger than 70 v ≥ 70 years ) , response ( PR v CR ) after R-CHOP , and positron emission tomography status at assignment ( negative v positive ) . With longer median follow-up of 52 months ( October 2016 ) , overall survival was similar between arms ( hazard ratio , 1.218 ; 95 % CI , 0.861 to 1.721 ; P = .26 ) . Most common grade 3 or 4 adverse events associated with lenalidomide versus placebo maintenance were neutropenia ( 56 % v 22 % ) and cutaneous reactions ( 5 % v 1 % ) , respectively . Conclusion Lenalidomide maintenance for 24 months after obtaining a CR or PR to R-CHOP significantly prolonged PFS in elderly patients with DLBCL Diffuse large B-cell lymphoma ( DLBCL ) is a heterogeneous entity , with patients exhibiting a wide range of outcomes . The addition of rituximab to CHOP chemotherapy (R-CHOP)has led to a marked improvement in survival and has called into question the significance of previously recognized prognostic markers . Since r and omized controlled trials of R-CHOP in DLBCL have included select subgroups of patients , the utility of the International Prognostic Index ( IPI ) has not been reassessed . We performed a retrospective analysis of patients with DLBCL treated with R-CHOP in the province of British Columbia to assess the value of the IPI in the era of immunochemotherapy . The IPI remains predictive , but it identifies only 2 risk groups . Redistribution of the IPI factors into a revised IPI ( R-IPI ) provides a more clinical ly useful prediction of outcome . The R-IPI identifies 3 distinct prognostic groups with a very good ( 4-year progression-free survival [ PFS ] 94 % , overall survival [ OS ] 94 % ) , good ( 4-year PFS 80 % , OS 79 % ) , and poor ( 4-year PFS 53 % , OS 55 % ) outcome , respectively ( P < .001 ) . The IPI ( or R-IPI ) no longer identifies a risk group with less than a 50 % chance of survival . In the era of R-CHOP treatment , the R-IPI is a clinical ly useful prognostic index that may help guide treatment planning and interpretation of clinical trials OBJECTIVES We conducted a r and omized clinical trial to evaluate the role of interferon alfa 2b ( IFN ) as maintenance therapy in patients with diffuse large B-cell lymphoma with high or high-intermediate clinical risk on complete remission ( CR ) after CHOP-BLEO regimens . METHODS Patients were initially treated with CHOP-BLEO regimens ( which include increased doses of cyclophosphamide and epirubicine , instead of doxorubicin ) . If the patients achieved CR they were r and omly assigned to receive either maintenance therapy with IFN 5.0 MU , three times at week by 1 yr , or no treatment ( control group ) . RESULTS Two hundred and twenty-three patients were considered as c and i date s for the study . They were of high ( 80 % ) or high-intermediate ( 20 % ) clinical risk ; additionaly most patients had poor prognostic factors such as high levels of beta 2 microglobulin , lactic dehydrogenase levels , bulky disease ( defined as a tumor mass > 10 cm ) or multiple extranodal involvement . In an intent-to-treat analysis all patients were evaluable to efficacy and toxicity . Median follow-up was 45 months , the estimated 5-yr overall survival and event-free survival ( EFS ) for patients who received IFN were 71 % ( 95 % confidence interval ( CI ) : 61 - 83 % ) and 57 % ( 95 % CI : 39 - 69 % ) , respectively , values which were not statistically different from the control group : 69 % ( 95 % CI : 63 - 79 % ) and 54 % ( 95 % CI : 37 - 63 % ) , respectively ( p=0.2 ) . Toxicity was mild . CONCLUSIONS These results suggest that IFN used as maintenance therapy at these doses and schedules is not useful in aggressive malignant lymphoma when more intensive chemotherapy has been employed during induction treatment . Nevertheless , follow-up is too short , and long-term follow-up would be necessary in order to draw definitive conclusions . Probably , an multicenter study is necessary to define the role of IFN as maintenance therapy in this patient setting Maintenance therapy in patients with aggressive malignant lymphoma using biological modifiers remains uncertain . We conducted a controlled clinical trial to evaluate the efficacy and toxicity of interferon-alpha 2b , cyclophosphamide , and prednisone as maintenance therapy in patients with aggressive diffuse large B cell lymphomas in complete remission after aggressive chemotherapy . In an intent-to-treat analysis , 169 patients were eligible for this study ; the end points were event-free survival ( EFS ) and overall survival ( OS ) . With a median follow-up of 49.3 months , no statistical differences were observed and actuarial curves at 5 years showed that EFS was 71 % ( 95 % confidence interval [ CI ] , 63 - 79 % ) for patients who received maintenance compared to 63 % ( 95 % CI , 59 - 71 % ) for patients in control group ( p = 0.05 ) . No statistical differences were observed in OS between maintenance arm : 84 % ( 95 % CI , 78 - 89 % ) and control group 83 % ( 95 % CI , 77 - 88 % ) in control group ( p = 0.2 ) . All patients received the maintenance therapy as planned and in time , thus dose intensity was considered 1.0 in all cases . Acute toxicity was mild , and no delay or suspension of treatment was necessary . Late toxicity was not evident until now . We conclude that use of maintenance therapy combining interferon-alpha 2b , cyclophosphamide , and prednisone is not useful in patients with aggressive lymphoma if they had been treated with aggressive combined chemotherapy To assess the efficacy and toxicity of interferon alfa 2b ( IFN ) as maintenance therapy in patients with malignant lymphoma on complete response after conventional chemotherapy we start a r and omized clinical trial . One hundred and seventy patients were r and omized to received either IFN 5.0 MU three time at week by one year or no further treatment , as control group . At a median follow-up of 9.0 years ( range 4.3 to 11 years ) median freedom from relapse ( FFR ) has not been reached in patients who received IFN , it is statistically significant to patients in control group with a median FFR of 60 months ( p < .001 ) . Actuarial curves show that at 10-years , 58 patients ( 66 % , 95 % confidence interval ( CI ) 53 % to 79 % ) remain in first remission , statistical different to control group 33 patients ( 40 % , 95 % Cl : 33 % to 57 % ) ( p < .001 ) . Event free survival ( EFS ) shown that a 10-years 63 patients ( 71 % , 95 % CI : 59 % to 81 % ) are alive free of disease in the IFN arm compared to only 38 patients ( 45 % , 95 % CI : 37 % to 57 % ) in the control group ( p < .001 ) . Toxicity was mild , 81 patients received the planned doses of IFN on time and 6 patients had transitory delay secondary to hematological toxicity ( grade 1 or 2 ) and completed the treatment on 13 months . No late side effects has been observed . After a long term follow-up we confirm that IFN used as maintenance therapy improves outcome in patients with aggressive malignant lymphoma who were in complete remission after conventional chemotherapy without excessive toxicity . We feld that IFN will be consider in controlled clinical trials to define the role of this therapeutic option Background : The correlation between efficacy end points in r and omized controlled trials ( RCTs ) of systemic therapy for non-Hodgkin 's lymphoma ( NHL ) was investigated to identify an appropriate surrogate end point for overall survival ( OS ) Output:	MT in patients with DLBCL achieving CR or PR after induction therapy did not affect OS , yet it decreased relapse rate and improved disease control at the cost of higher infection rate . Our data do not support routine administration of MT in patients with DLBCL
MS21686	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Purpose The purpose of this study was to evaluate the efficacy and comparison between 2.0 mm locking plate system and 2.0 mm Champy ’s titanium mini plating system in m and ible fractures . Material s and Methods A total of 20 patients with m and ibular fractures were selected and divided into two groups A and B on r and omized basis . Group A was treated with open reduction internal fixation using 2.0 mm locking plates and group B with 2.0 mm Champy ’s titanium miniplates . All patients were followed up for 12 weeks postoperatively . Results Results of the study show less screw loosening , less precision in plate adaptation and less alteration of the osseous or occlusal relationship upon screw tightening in group A. Chi square test was applied to compare the results between the two groups . Statistical analysis did not show significant difference of incidence of malocclusion between the two groups ( p value = 0.606 ) . Statistical analysis using un-paired t test showed significant difference of working time between the two groups ( p value = 0.00296 ) . When comparing the overall complication rates according to plates used , the χ2 test showed no statistically significant difference between the locking and nonlocking plates ( p > 0.05 ) . Conclusion It is observed in our study that the locking plate/screw system offers significant advantages over the conventional plating system . The precise adaptation required for using conventional plates is not needed when this locking plate/screw system is used . Locking plate/screw system provides better stability than the conventional plate/screw system Purpose The purpose of this clinical study was to compare effectiveness of 2.0-mm locking miniplates and screws with 2.0-mm st and ard miniplates and screws in treating m and ible fractures . Patients and methods A r and omized prospect i ve study comprising of 40 sample s , where 20 patients ( group 1 ) were treated with locking plates and 20 patients ( group 2 ) were treated with st and ard miniplates . All the cases were evaluated for the type of fracture , need for the Intermaxillary Fixation ( IMF ) and its duration , duration of surgery , anatomic reduction , paresthesia / neurosensory changes , occlusal discrepancies , infection at the fracture site and any need for the removal of the plates and screws . Results In our study Road Traffic Accidents ( RTA ) accounted for the majority of patients 30 ( 70 % ) . RTA was more prevalent ( 52.5 % ) in 21–30 age group , with assault being more common ( 67 % ) in 25–35 years . There was a significant difference between group 1 and 2 in postoperative occlusal discrepancy and need for IMF ( p=0.008 ) . There was no significant difference in complication rates between group 1 and group 2 patients . Conclusion Locking plate/screw system proved to be more rigid than conventional plate/ screw system , thereby reducing the need and duration of IMF . However there was no significant difference in complication rates To compare and evaluate the effectiveness of 2.0 mm locking miniplates versus 2.0 mm st and ard miniplates in treatment of m and ible fractures . Sixty r and omly selected patients who sustained m and ibular fractures were selected for this study . The fractured fragments were stabilized using 2.0 mm locking miniplates in 30 cases and in the remaining 30 cases the fractured fragments were fixed with conventional 2.0 mm miniplates . Post-operative stability was assessed with radiographs at 7th day , 1st , and 3rd months . The stability of the reduced fracture was assessed clinical ly and both the types of plates were assessed with an OPG or conventional radiographs . This study shows favorable results on use of locking miniplates in m and ibular fractures . The results show that there were no significant differences in the post-operative complications between the conventional and the locking plate/screw m and ibular systems . The locking plate/screw system was more rigid than conventional plate/screw system , thereby reducing the need and duration of intermaxillary fixation ( IMF ) PURPOSE The aim of this follow-up study was to compare 3-dimensional ( 3D ) and st and ard ( Champy 's ) miniplate fixation in the management of m and ibular fractures , and to analyze advantages and disadvantages of one over the other . PATIENTS AND METHODS A prospect i ve r and omized clinical trial was carried out in patients with well-defined inclusion and exclusion criteria . Patients were followed for 2 months for wound dehiscence , infection , segmental mobility , postoperative occlusion , significant period of postoperative complications , and radiological evaluation of reduction and fixation . RESULTS Twenty patients were enrolled in both the groups with no case of wound dehiscence . In group 1 , 2 patients had mild segmental mobility ( P = .07 ) , 2 patients had surgical site infection ( P = .07 ) , and 2 patients involving mental nerve had involved roots of teeth ( P = .07 ) . Radiological evaluation did not show any statistically significant difference in reduction ( P = 1.4 ) , but showed a significant difference ( P = .03 ) in fixation between the 2 groups , especially in cases involving the mental nerve ( ie , fracture near or involving the mental foramen ) and oblique fractures . CONCLUSION Champy 's miniplate system is a better and easier method than the 3D miniplate system for fixation of m and ibular fractures . In comparison , the 3D miniplate system is unfavorable for use in cases of oblique fractures and those involving the mental nerve , and is also difficult to adapt . In most cases , it provides good stability but with excessive implant material because of extra vertical bars incorporated for countering the torque forces . However , operative time is less because of simultaneous stabilization at both superior and inferior borders Introduction The purpose of this study was to compare the outcome of open treatment of m and ibular fracture ( symphysis or parasymphysis ) using lag screw or mini plate clinical ly as well as radiologically in young ( age range 12–45 years ) and healthy individuals of poor socioeconomic status . Method This prospect i ve study was conducted on 30 patients diagnosed as cases of displaced m and ibular anterior fractures treated with open reduction and internal fixation . The patients were then r and omly allocated to either of two groups––Group A : Two 2.5 mm stainless steel lag screws were placed in 15 patients . Group B : Two 2.5 mm stainless steel mini plates were placed in 15 patients for the fixation of fractures . Subsequent follow up was done on 2nd , 4th , 6th and 8th week postoperatively . During every follow up patient was assessed clinical ly for infection , malocclusion , loosening of plate/screw , sensory disturbance , plate fracture , malunion/non-union , devitalisation of associated dentoalveolar segment and masticatory efficiency . Radiographs were taken if necessary and patients were further assessed for any complaint . Pain was objective ly measured using a visual analogue scale , bite force was measured using a bite force transducer at biweekly interval . The data collected was subjected to unpaired t test and paired t test for statistical analysis . Results During follow up period a significant improvement in bite force was present in both the groups , with more improvement seen in the lag screw group ( p < 0.01 ) . There was a significant pain reduction present in the lag screw group ( p < 0.01 ) and also masticatory efficiency showed a steadier improvement in lag screw group while mini plate group patients showed a tendency to masticate only food items of medium hard consistency . Conclusion The sample size is small to conclude lag screws are better than mini plates but the result of our study provides a basis for further studies done to conclude that the application of LAG SCREW is an effective , inexpensive , quick treatment modality to accelerate healing of fresh , displaced m and ibular anterior fracture This prospect i ve r and omized clinical trial compared the treatment outcomes of strut plate and Champy miniplate in fixation of m and ibular angle fractures . Patients with m and ibular angle fracture were consented and enrolled into this study . Exclusion criteria include patients with severely comminuted fractures . The patients were r and omly assigned to receive the strut plate or Champy miniplate for angle fracture fixation . Patient demographics , fracture characteristics , operative and postoperative outcomes were collected prospect ively . Statistical analysis was performed to evaluate the significance of the outcome . A total of 18 patients were included in this study and r and omly assigned to receive either the strut plate or Champy miniplate . Out of which five patients were excluded postoperatively due to complex fracture result ing in postoperative maxillom and ibular fixation . The final enrollment was 13 patients , N = 6 ( strut ) and N = 7 ( Champy ) . There was no statistically significant difference in the pretreatment variables . Nine of these patients had other associated facial fractures , including parasymphyseal and subcondylar fractures . Most of the ( 11 ) patients had sufficient follow-up after surgery . Both groups exhibited successful clinical unions of the m and ibular angle fractures . The complications associated with the m and ibular angle were 20 % in the strut plate group and 16.7 % in the Champy group . One patient in the strut plate group had a parasymphyseal infection , requiring hardware removal . The strut plate demonstrated comparable surgical outcome as the Champy miniplate . It is a safe and effective alternative for management of m and ibular angle fracture Introduction Three dimensional titanium plating system was developed by Farm and in 1995 to meet the requirements of semi rigid fixation with lesser complication . The purpose of this in vivo prospect i ve study was to evaluate and compare the clinical effectiveness of three dimensional and two dimensional Titanium miniplates for open reduction and fixation of m and ibular parasymphysis fracture . Material s and Methods Thirty patients with non-comminuted m and ibular parasymphysis fractures were divided r and omly into two equal groups and were treated with 2 mm 3D and 2D miniplate system respectively . All patients were systematic ally monitored at 1st , 2nd , 3rd , 6th week , 3rd and 6th month postoperatively . The outcome parameters recorded were severity of pain , infection , mobility , occlusion derangement , paresthesia and implant failure . The data so collected was analyzed using independent t test and Chi square test ( α = .05 ) . Results The results showed that one patient in each group had post-operative infection , occlusion derangement and mobility ( p > .05 ) . In Group A , one patient had paresthesia while in Group B , two patients had paresthesia ( p > .05 ) . None of the patients in both the groups had implant failure . There was no statistically significant difference between 3D and 2D miniplate system in all the recorded parameters at all the follow-ups ( p > .05 ) . Conclusion 3D miniplates were found to be better than 2D miniplates in terms of cost , ease of surgery and operative time . However , 3D miniplates were unfavorable for cases where fracture line was oblique and in close proximity to mental foramen , where they were difficult to adapt and more chances for tooth-root damage and inadvertent injury to the mental nerve due to traction This study evaluated the efficacy of a 2.0-mm locking plate/screw system compared with a 2.0-mm non-locking plate/screw system in m and ibular fractures . A prospect i ve r and omized clinical trial was conducted . Patients were r and omly assigned to receive 2.0-mm locking plates ( group A ) or 2.0-mm nonlocking plates ( group B ) . All patients were followed up for 12 weeks postoperatively . Complications were analysed according to the type of plate used and the site of fracture . Fifty patients with 76 fractures met the inclusion criteria . Thirty-six fracture sites were treated with 2.0-mm locking plates and 40 with 2.0-mm nonlocking plates . The number of patients requiring postoperative maxillom and ibular fixation was significantly higher in group B ( p < 0.01 ) ; seven complications occurred representing 9 % of the total . Two complications occurred in the locking group and five in the nonlocking group with complication rates equalling 6 % and 13 % , respectively . When comparing the overall complication rates according to plates used , the χ(2 ) test showed no statistically significant difference between the locking and nonlocking plates ( p > 0.05 ) . In conclusion , m and ible fractures treated with 2.0-mm locking plates and 2.0-mm nonlocking plates present similar short-term complication rates The objective of this study is to analyze the difference in bite forces in patients treated for m and ibular fractures with 2.0 mm conventional and locking titanium plating system . A r and omized study was performed for the treatment of fractures of m and ible . In this study , 20 adult patients with isolated m and ibular fracture were included . The patients were r and omly allocated into two groups , that is , Group I-2.0 mm nonlocking ( traditional ) and Group II-2.0 mm locking plates . Bite force was evaluated at 1st , 3rd , and 6th weeks . Comparison of all the assessed parameters between both the groups depicted no significant difference in terms of pain , swelling including the incidence of infection , paresthesia , and hardware failure . Although same was true in case of bite force between both the groups at various time intervals , there was statistically significant increase in the bite force within the group comprising patients in whom locking plates was used between 1st and 3rd weeks follow-up period and highly significant increase in bite force between 1st and 6th weeks of follow-up period . The rapid improvement of bite force values when locking plates Output:	Conclusion The results of the three-Dimensional Versus St and ard miniplate showed that 3-dimensional miniplate is the best option for m and ibular fractures . Regarding Lag Screws Versus Miniplates results of the meta- analysis found that the use of lag screws is superior to using miniplates in reducing the incidence of postoperative complications . And in regards to locking miniplates versus non-locking miniplate , the analysis indicates that the 2.0-mm locking miniplate is a prospect i ve fixation system in the treatment of maxillofacial fractures
MS21687	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE The purpose of this study was to compare the efficacy and side effects of two different misoprostol regimens for second-trimester pregnancy termination . STUDY DESIGN We performed a r and omized clinical trial in patients who were at 14 to 23 weeks of gestation and who were admitted for medical termination of pregnancy . All patients received 800 microg of vaginal misoprostol and were assigned r and omly to 400 microg of oral misoprostol or 400 microg of vaginal misoprostol every 8 hours . Efficacy and side effects were compared . The mean induction time of the study group was compared with that of an historic control group that had received 400 microg vaginally every 12 hours . RESULTS Forty-three women were assigned r and omly , 22 women to vaginal misoprostol and 21 women to oral misoprostol . Induction time and hospital stay were slightly shorter for the oral group ; however , the differences were not significant . Side effects were similar for both groups . CONCLUSION After an initial 800 microg dose of vaginal misoprostol , a regimen of 400 microg of oral misoprostol every 8 hours is as effective as the same dose of vaginal misoprostol with no additional side effects , which provides a convenient alternative for midtrimester pregnancy termination OBJECTIVE The purpose of this study was to compare the clinical efficacy and side effects of 3 doses of intravaginal misoprostol for second-trimester pregnancy termination . STUDY DESIGN This was a prospect i ve r and omized , double-blind controlled clinical trial of 150 women who underwent pregnancy termination between 14 and 30 weeks of gestation . Three intravaginal misoprostol regimens were compared : 200 microg misoprostol at 6-hour intervals ( group 1 ) , 400 microg misoprostol at 6-hour intervals ( group 2 ) , and a loading dose of 600 microg misoprostol followed by 200 microg at 6-hour intervals ( group 3 ) . RESULTS There was a significant difference in the median time to achieve delivery among the 3 groups : group 1 ( 18.2 hours [ IQ , 13.3 - 32.5 hours ] ) vs group 2 ( 15.1 hours [ IQ , 10.9 - 23.7 hours ] ) vs group 3 ( 13.2 hours [ IQ , 11.2 - 21.7 hours ] ; P = .035 ) . Fifty-nine percent of the women in group 1 , 76 % of the women in group 2 , and 80 % of the women in group 3 delivered within 24 hours ( P = .013 ) . There were 7.8 % of the women in group 1 , 0 % of the women in group 2 , and 2 % of the women in group 3 who were undelivered at 48 hours ( P = .02 ) . There was an increase in the incidence of fever in the first 12 hours ( P = .038 ) and in the incidence of vomiting within 3 hours of the initial dose ( P = .048 ) in group 3 compared with the other groups . CONCLUSION Intravaginal misoprostol 400 microg at 6-hour intervals appears to be the preferred regimen for second-trimester pregnancy termination , with a shorter commencement to delivery interval than the 200 microg regimen and fewer maternal side-effects than the 600 microg loading dose regimen OBJECTIVE To compare the efficacy of vaginal and oral misoprostol for the induction of labour in women with intra-uterine foetal death ( IUFD ) . DESIGN A prospect i ve r and omised clinical trial , comparing 200 microg oral and 200 microg vaginal misoprostol , six hourly for a maximum of four doses for the induction of labour in women with IUFD . SETTING Ga-Rankuwa hospital ( Department of Obstetrics and Gynaecology ) , Pretoria , South Africa . It is a tertiary institution serving predominantly black indigenous population . MAIN OUTCOME MEASURES The primary outcome measure was the induction to delivery time , and secondary outcome measures were the number of patients requiring augmentation with oxytocin and all complications were noted . RESULTS Twenty women were r and omised to the vaginal route and 18 to the oral route . The induction to delivery time was shorter with vaginal misoprostol ( 13.5 + /- 8.3 hrs ) compared to oral misoprostol ( 21.4 + /- 13.9 hrs ; p < 0.05 ) . There was no significant difference in the amount of misoprostol needed to achieve successful induction in the two groups . More women ( 10/18 ) who received oral misoprostol required oxytocin augmentation to complete the induction of labour compared with 4/20 women in the vaginal group ( p < 0.05 ; Odds Ratio 2.8 ; 95 % Cl 1.36 - 4.24 ) . There were no cases of failed induction . The systemic side effects ( shivering , diarrhoea , vomiting and pyrexia ) were more common with oral misoprostol ( 44.5 % ) compared to vaginal misoprostol ( 20 % ) . This difference gives an overall Odds Ratio of 2.2 at 95 % Cl of 1.6 - 2.8(p < 0.05 ) . CONCLUSION Vaginal misoprostol achieved successful induction of labour in women with IUFD in a shorter time than oral misoprostol with significantly less side effects Summary Gemeprost ( Cervagem ) has been used widely compared with Misoprostol ( Cytotec ) alone in second trimester pregnancy termination . This prospect i ve r and omised trial was to evaluate the efficacy of intravaginal Misoprostol ( alone ) and Gemeprost in second trimester termination of pregnancy . A total of 54 women with 27 on each arm were involved . A total of 25 patients ( 92.6 % ) in the Misoprostol group and 22 patients ( 81.5 % ) in the Gemeprost group delivered within 48 h. The Misoprostol group delivered earlier , although average number of tablets required were similar . The side-effects were not significant between the two groups in fact , but there was more pyrexia in the Gemeprost group ( p = 0.004 ) . Misoprostol in second trimester termination of pregnancy is clinical ly as effective and less costly than the st and ard regimen of Gemeprost The object of this study was to compare intravaginal misoprostol and dinoprostone ( prostagl and in E2 ) for second-trimester pregnancy termination , and to examine the role of the nitric oxide donor , glyceryl trinitrate , as a possible alternative to prostagl and ins to induce cervical ripening in second-trimester pregnancy termination . This was a r and omised clinical trial . The trial involved pregnant women between 13 and 28 weeks ' gestation admitted with clear medical or obstetric indications for pregnancy termination , and was carried out in the department of obstetrics and gynecology , Assiut University Hospital , Egypt . Patients were classified into Group A , where pregnancy termination was induced by vaginal misoprostol 100 micrograms every 4 hours with a maximum dose of 500 micrograms ; Group B , where induction was by vaginal dinoprostone 6 mg every 6 hours with a maximum dose of 24 mg ; and Group C , where induction involved vaginal glyceryl trinitrate 500 micrograms every 6 hours with a maximum dose of 2.5 mg . Twenty-four hours after the start of induction , the rate of complete abortion in the three groups was 100 % , 66.67 % and 0 % , respectively . The rate of complete abortion was 100 % in the nitric oxide ( glyceryl trinitrate)-induced group after introducing a complementary procedure . The induction – abortion interval was significantly shorter , the number of doses needed was less and the maximum Bishop score reached was greater with misoprostol than with dinoprostone . A higher rate of side effects occurred with the misoprostol-induced group ( 74 % ) compared with the other two groups ( 46.6 % and 0 % ) . Misoprostol is a cheap , effective drug for second-trimester pregnancy termination with short induction abortion intervals but a higher rate of side effects . Prostin E2 is also effective in termination of second-trimester pregnancy but is expensive and may require high doses to be administered . Glyceryl trinitrate is an effective drug for cervical ripening ( softening ) but it has no role in the stimulation of uterine contractions Objective To compare the effectiveness of vaginal misoprostol administered 6 or 12 hourly for second trimester pregnancy termination OBJECTIVE To evaluate the induction-to-abortion time of 3 pharmacokinetic-based protocol s at 13 - 20 weeks of gestation . STUDY DESIGN A r and omized trial was conducted on 153 patients . The oral group ( n = 51 ) received 100 microg misoprostol orally every 2 hours , the vaginal group ( n = 51 ) received 200 microg misoprostol vaginally every 4 hours , and the sublingual group ( n = 51 ) received 100 microg misoprostol sublingually every 2 hours . RESULTS The mean induction-to-delivery time was shorter in the sublingual group ( mean , 651 + /- 507 ) as compared to the vaginal group ( mean , 1,056 + /- 634 , p = 0.01 ) . The number of patients who delivered within 12 hours was significantly higher in the sublingual group ( n = 39 , 78 % ) as compared to the oral ( n = 26 , 52 % ) and vaginal ( n = 20 , 40 % ) groups ( p < 0.001 ) . The numbers of patients who delivered within 24 hours were comparable in the sublingual ( n = 47 , 94 % ) and oral ( n = 46 , 92 % ) groups but higher than in the vaginal group ( n = 39 , 78 % ; p = 0.02 ) . The total misoprostol dose was 543 + /- 422 microg in the sublingual group , 878 + /- 533 microg in the vaginal group and 741 + /- 413 microg in the oral group ( p < 0.001 ) . CONCLUSION A pharmacokinetic-based application of 100 microg of sublingual misoprostol every 4 hours is more effective for induction of second-trimester abortion as compared to 100 microg oral misoprostol every 2 hours and 200 microg vaginal misoprostol every 4 hours Objective : To compare the efficacy of a combined regimen of misoprostol with vaginal misoprostol for early 2nd-trimester pregnancy termination . Methods : This is a prospect i ve study that includes 79 pregnant women who requested legal termination of 2nd-trimester pregnancy between 13 and 22 weeks . Two regimens of misoprostol were used . Group 1 : 400 µg of oral plus 400 µg vaginal misoprostol every 8 h ( combined regimen ) and group 2 : 400 µg of vaginal misoprostol every 3 h up to a maximum of five doses ( vaginal regimen ) . Results : The induction-to-abortion interval was significantly longer in group 1 ( 25.5 ± 24.45 h ) than in group 2 ( 15 ± 7.14 h ) ( p = 0.016 ) . The abortion rate within 24 h in group 1 was of 56.8 vs. 85.7 % in group 2 ( p = 0.006 ) . The hazard rate for vaginal delivery within 24 h was found to be 2.277-fold greater in the group with the combined therapy once controlled for plausible confounders . Conclusions : Our study suggests that oral misoprostol combined with vaginal misoprostol does not reduce the induction-to-abortion interval compared to an exclusively vaginal route when used for early 2nd-trimester pregnancy termination BACKGROUND Intrauterine fetal death is a major problem in obstetrics particularly in developing countries such as Ug and a. Induction of labour in cases of fetal death using the available method of oxytocin is often difficult , expensive and frustrating . OBJECTIVES To compare the effectiveness of vaginal misoprostol and intravenous oxytocin in induction of labour in women with intrauterine fetal death . METHODS One hundred and twenty mothers were allocated in a r and omised controlled way to one of the two induction groups . Oxytocin infusion was titrated based on patient response . The starting dose was 50 mcg ( 1/4 tablet ) in misoprostol group and the dose was doubled every six hours till effective contractions were achieved . The two groups were compared for induction to delivery intervals , costs of the drugs and their safety during induction . RESULTS The success rate within 48 hours of induction was 100 % in the misoprostol group and 96.7 % in oxytocin group . The mean induction to delivery time was significantly longer in the oxytocin group compared with the misoprostol group ( 23.3 versus 12.4 hours ; p= 0.004 ) . In the gestational age before 28 Output:	MAIN RESULTS We included 38 studies ( 3679 women).Nine studies included pregnancies after intrauterine deaths , five studies included termination of pregnancies because of fetal anomalies when the fetus was still alive and the rest ( 24 ) presented the pooled data for intrauterine deaths , fetal anomalies and social reasons .When compared with agents that have traditionally been used to induce labour in this setting ( for example , gemeprost , prostagl and in E(2 ) and prostagl and in F(2alpha ) ) , vaginal misoprostol is as effective in ensuring vaginal birth within 24 hours , with a similar induction to birth interval . Vaginal misoprostol is associated with a reduction in the occurrence of maternal gastrointestinal side effects such as nausea , vomiting and diarrhoea when compared with other prostagl and in preparations . While the different treatments involving various prostagl and in preparations appear comparable for the reported outcomes , the information available regarding rare maternal complications , such as uterine rupture , is limited . The use of vaginal misoprostol in the termination of second and third trimester of pregnancy is as effective as other prostagl and in preparations ( including cervagem , prostagl and in E(2 ) and prostagl and in F(2alpha ) ) , and more effective than oral administration of misoprostol .
MS21688	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Purpose : Patients with progressive or recurrent supratentorial high- grade gliomas were entered into a multicentre phase II trial to evaluate the efficacy and toxicity of temozolomide . Methods : The treatment schedule was 150–200 mg/m2 per day orally for 5 days repeated every 28 days . Response evaluation was by a combination of neurological status evaluation ( MRC scale ) and imaging . Results : Of 103 eligible patients enrolled , 11 ( 11 % ) achieved an objective response and a further 48 ( 47 % ) had stable disease . The median response duration was 4.6 months . Response rates were similar for anaplastic astrocytomas ( grade III ) and glioblastoma multiforme ( grade IV ) tumours . Predictable myelosuppression was the major toxicity . Conclusions : The observation of objective responses and tolerable side effects in this heterogeneous population of patients supports the further investigation of this agent in high- grade gliomas PURPOSE The st and ard of care for anaplastic gliomas is surgery followed by radiotherapy . The NOA-04 phase III trial compared efficacy and safety of radiotherapy followed by chemotherapy at progression with the reverse sequence in patients with newly diagnosed anaplastic gliomas . PATIENTS AND METHODS Patients ( N = 318 ) were r and omly assigned 2:1:1 ( A : B1:B2 ) to receive conventional radiotherapy ( arm A ) ; procarbazine , lomustine ( CCNU ) , and vincristine ( PCV ; arm B1 ) ; or temozolomide ( arm B2 ) at diagnosis . At occurrence of unacceptable toxicity or disease progression , patients in arm A were treated with PCV or temozolomide ( 1:1 r and om assignment ) , whereas patients in arms B1 or B2 received radiotherapy . The primary end point was time to treatment failure ( TTF ) , defined as progression after radiotherapy and one chemotherapy in either sequence . RESULTS Patient characteristics in the intention-to-treat population ( n = 274 ) were balanced between arms . All histologic diagnoses were central ly confirmed . Median TTF ( hazard ratio [ HR ] = 1.2 ; 95 % CI , 0.8 to 1.8 ) , progression-free survival ( PFS ; HR = 1.0 ; 95 % CI , 0.7 to 1.3 , and overall survival ( HR = 1.2 ; 95 % CI , 0.8 to 1.9 ) were similar for arms A and B1/B2 . Extent of resection was an important prognosticator . Anaplastic oligodendrogliomas and oligoastrocytomas share the same , better prognosis than anaplastic astrocytomas . Hypermethylation of the O(6)-methylguanine DNA-methyltransferase ( MGMT ) promoter ( HR = 0.59 ; 95 % CI , 0.36 to 1.0 ) , mutations of the isocitrate dehydrogenase ( IDH1 ) gene ( HR = 0.48 ; 95 % CI , 0.29 to 0.77 ) , and oligodendroglial histology ( HR = 0.33 ; 95 % CI , 0.2 to 0.55 ) reduced the risk of progression . Hypermethylation of the MGMT promoter was associated with prolonged PFS in the chemotherapy and radiotherapy arm . CONCLUSION Initial radiotherapy or chemotherapy achieved comparable results in patients with anaplastic gliomas . IDH1 mutations are a novel positive prognostic factor in anaplastic gliomas , with a favorable impact stronger than that of 1p/19q codeletion or MGMT promoter methylation A r and omized , multicentre , open-label , phase II study compared temozolomide ( TMZ ) , an oral second-generation alkylating agent , and procarbazine ( PCB ) in 225 patients with glioblastoma multiforme at first relapse . Primary objectives were to determine progression-free survival ( PFS ) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment . Secondary objectives were to assess overall survival and health-related quality of life ( HRQL ) . TMZ was given orally at 200 mg/m2/day or 150 mg/m2/day ( prior chemotherapy ) for 5 days , repeated every 28 days . PCB was given orally at 150 mg/m2/day or 125 mg/m2/day ( prior chemotherapy ) for 28 days , repeated every 56 days . HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 [ + 3 ] ) and the Brain Cancer Module 20 ( BCM20 ) . The 6-month PFS rate for patients who received TMZ was 21 % , which met the protocol objective . The 6-month PFS rate for those who received PCB was 8 % ( P = 0.008 , for the comparison ) . Overall PFS significantly improved with TMZ , with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group ( P = 0.0063 ) . The 6-month overall survival rate for TMZ patients was 60 % vs. 44 % for PCB patients ( P = 0.019 ) . Freedom from disease progression was associated with maintenance of HRQL , regardless of treatment received . TMZ had an acceptable safety profile ; most adverse events were mild or moderate in severity . © 2000 Cancer Research BACKGROUND Oligodendroglial tumors are chemosensitive , with two-thirds of patients responding to PCV combination chemotherapy with procarbazine , lomustine ( CCNU ) and vincristine . Temozolomide ( TMZ ) , a new alkylating and methylating agent has shown high response rates in recurrent anaplastic astrocytoma . We investigated this drug in recurrent oligodendroglial tumors ( OD ) and mixed oligoastrocytomas ( OA ) after prior PCV chemotherapy and radiation therapy . PATIENTS AND METHODS In a prospect i ve non-r and omized multicenter phase II trial patients were treated with TMZ 150 mg/m(2 ) on days 1 - 5 in cycles of 28 days for 12 cycles . Eligible patients had a recurrence after prior PCV chemotherapy , with measurable and enhancing disease as shown by magnetic resonance imaging . Pathology and all responses were central ly review ed . RESULTS Thirty-two eligible patients were included . In four patients the pathology review did not confirm the presence of an OD or OA . Twelve of 24 patients [ 50 % , 95 % confidence interval ( CI ) 29 % to 71 % ] evaluable for response to first-line PCV chemotherapy had responded to PCV . Temozolomide was in general well tolerated ; the most frequent side-effects were hematological . One patient discontinued treatment due to toxicity . In seven of 28 patients ( 25 % , 95 % CI 11 % to 45 % ) with histologically confirmed OD an objective response to TMZ was observed . Median time to progression for responding patients was 8.0 months . After 6 and 12 months from the start of treatment , 29 % and 11 % of patients , respectively , were still free from progression . CONCLUSIONS TMZ may be regarded as the preferred second-line treatment in OD after failure of PCV chemotherapy . Further studies on TMZ in OD are indicated The authors investigated the results of PCV chemotherapy within a cohort of 24 patients treated within the EORTC study 26971 on temozolomide chemotherapy in recurrent oligodendroglioma . The genotype of the tumors was assessed with fluorescent in situ hybridization with locus specific probes for the region 1p36 . Four of the 24 patients responded ( 17 % ) . Fifty percent of patients were still free from progression at 6 months and 21 % were free from progression at 12 months . Although a clear relation existed between loss of 1p and response to temozolomide chemotherapy , this relation was absent in salvage PCV chemotherapy PURPOSE Temozolomide ( TMZ ) is an alkylating agent licensed for treatment of high- grade glioma ( HGG ) . No prospect i ve comparison with nitrosourea-based chemotherapy exists . We report , to our knowledge , the first r and omized trial of procarbazine , lomustine , and vincristine ( PCV ) versus TMZ in chemotherapy-naive patients with recurrent HGG . PATIENTS AND METHODS Four hundred forty-seven patients were r and omly assigned to PCV ( 224 patients ) or TMZ ( sub-r and om assignment : TMZ-5 [ 200 mg/m(2 ) for 5 days , 112 patients ] or TMZ-21 [ 100 mg/m(2 ) for 21 days , 111 patients ] ) for up to 9 months or until progression . The primary outcomes were survival ( PCV v TMZ ) and 12-week progression-free survival ( PFS ; TMZ-5 v TMZ-21 ) . This study is registered as IS RCT N83176944 . RESULTS Percentages of patients completing 9 months of treatment in the PCV , TMZ-5 , and TMZ-21 arms were 17 % , 26 % , and 13 % , respectively . Major toxicity was similar across all three groups . With a median follow-up time of 12 months and 382 deaths , there was no clear survival benefit when comparing PCV with TMZ ( hazard ratio [ HR ] , 0.91 ; 95 % CI , 0.74 to 1.11 ; P = .350 ) . For TMZ-5 versus TMZ-21 , 12-week PFS rates were similar ( 63.6 % and 65.7 % , respectively ; P = .745 ) , but TMZ-5 improved overall PFS ( HR , 1.38 ; 95 % CI , 1.05 to 1.82 ; P = .023 ) , survival ( HR , 1.32 ; 95 % CI , 0.99 to 1.75 ; P = .056 ) , and global quality of life ( 49 % v 19 % improved > 10 points at 6 months , respectively ; P = .005 ) . CONCLUSION Although TMZ ( both arms combined ) did not show a clear benefit compared with PCV , comparison of the TMZ schedules demonstrated that the 21-day schedule was inferior to the 5-day schedule in this setting . This challenges the current underst and ing of increasing TMZ dose-intensity by prolonged scheduling PURPOSE Anaplastic oligodendroglioma are chemotherapy-sensitive tumors . We now present the long-term follow-up findings of a r and omized phase III study on the addition of six cycles of procarbazine , lomustine , and vincristine ( PCV ) chemotherapy to radiotherapy ( RT ) . PATIENTS AND METHODS Adult patients with newly diagnosed anaplastic oligodendroglial tumors were r and omly assigned to either 59.4 Gy of RT or the same RT followed by six cycles of adjuvant PCV . An exploratory analysis of the correlation between 1p/19q status and survival was part of the study . Retrospectively , the methylation status of the methyl-guanine methyl transferase gene promoter and the mutational status of the isocitrate dehydrogenase ( IDH ) gene were determined . The primary end points were overall survival ( OS ) and progression-free survival based on intent-to-treat analysis . RESULTS A total of 368 patients were enrolled . With a median follow-up of 140 months , OS in the RT/PCV arm was significantly longer ( 42.3 v 30.6 months in the RT arm , hazard ratio [ HR ] , 0.75 ; 95 % CI , 0.60 to 0.95 ) . In the 80 patients with a 1p/19q codeletion , OS was increased , with a trend toward more benefit from adjuvant PCV ( OS not reached in the RT/PCV group v 112 months in the RT group ; HR , 0.56 ; 95 % CI , 0.31 to 1.03 ) . IDH mutational status was also of prognostic significance . CONCLUSION The addition of six cycles of PCV after 59.4 Gy of RT increases both OS and PFS in anaplastic oligodendroglial tumors . 1p/19q-codeleted tumors derive more benefit from adjuvant PCV compared with non-1p/19q-deleted tumors The goal of this study was to determine the antitumor activity and toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea ( BCNU ) plus recombinant interferon-alpha ( IFN-alpha ) in patients with recurrent glioma . As single agents , both BCNU and IFN-alpha can cause tumor regression in patients with recurrent glioma . In vitro studies suggest synergy between the two agents . Thirty-five patients in whom computerized tomography ( CT ) or magnetic resonance ( MR ) evidence was obtained of progressive astrocytoma , oligoastrocytoma , or oligodendroglioma received recombinant IFN-alpha 2a Output:	Chemotherapy-naive patients with HGG at first recurrence when treated with PCV or TMZ have similar survival and time-to-progression outcomes . Adverse events are similar and QoL scores are statistically but not clinical ly significant between TMZ and PCV .
MS21689	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Omega-3 fatty acids , such as those present in fish oil , have been reported to prolong life in myocardial infa rct ion survivors . These fatty acids can decrease serum triglyceride concentrations , but so far the doses used in trials examining their effects on coronary end points have had only minimal triglyceride lowering effects . OBJECTIVE To examine the triglyceride lowering effectiveness , safety , and tolerability of Omacor , a concentrate of omega-3 , long chain , polyunsaturated fatty acids from fish oil ( 84 % of the total as opposed to an average of 35 % in fish oil ) over one year in patients with established coronary heart disease ( CHD ) and persisting hypertriglyceridaemia , despite receiving simvastatin in doses similar to those employed in the Sc and inavian simvastatin survival study . SUBJECTS AND METHODS 59 patients with CHD , receiving simvastatin 10–40 mg daily with serum triglycerides > 2.3 mmol/l , were r and omised to receive Omacor 2 g twice a day or placebo for 24 weeks in a double blind trial . Forty six patients accepted the offer of active treatment for a further 24 weeks in an open phase of the trial . RESULTS There was a sustained significant decrease in serum triglycerides by 20–30 % ( p < 0.005 ) and in very low density lipoprotein ( VLDL ) cholesterol by 30–40 % ( p < 0.005 ) in patients receiving active Omacor at three , six , and 12 months compared either to baseline or placebo . Omacor did not have any deleterious effect on low density or high density lipoprotein cholesterol or on biochemical and haematological safety tests . There was no adverse effect on glycaemic control in patients with diabetes , who showed a decrease in serum triglyceride , which was at least as great as in non-diabetic patients . One patient receiving placebo died of acute myocardial infa rct ion . Three patients withdrew from the trial ( two on placebo and one on active treatment ) . Omacor was generally well tolerated . CONCLUSION Omacor was found to be a safe and effective means of lowering serum triglycerides over one year in patients with CHD and combined hyperlipidaemia , whose triglycerides remained elevated despite simvastatin treatment BACKGROUND We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas , which are precursors of most large-bowel cancers . METHODS We r and omly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before r and omization to one of two groups : an intervention group given intensive counseling and assigned to follow a diet that was low in fat ( 20 percent of total calories ) and high in fiber ( 18 g of dietary fiber per 1000 kcal ) and fruits and vegetables ( 3.5 servings per 1000 kcal ) , and a control group given a st and ard brochure on healthy eating and assigned to follow their usual diet . Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps ; they remained in the study for approximately four years , undergoing colonoscopy one and four years after r and omization . RESULTS A total of 1905 of the r and omized subjects ( 91.6 percent ) completed the study . Of the 958 subjects in the intervention group and the 947 in the control group who completed the study , 39.7 percent and 39.5 percent , respectively , had at least one recurrent adenoma ; the unadjusted risk ratio was 1.00 ( 95 percent confidence interval , 0.90 to 1.12 ) . Among subjects with recurrent adenomas , the mean ( + /-SE ) number of such lesions was 1.85+/-0.08 in the intervention group and 1.84+/-0.07 in the control group . The rate of recurrence of large adenomas ( with a maximal diameter of at least 1 cm ) and advanced adenomas ( defined as lesions that had a maximal diameter of at least 1 cm or at least 25 percent villous elements or evidence of high- grade dysplasia , including carcinoma ) did not differ significantly between the two groups . CONCLUSIONS Adopting a diet that is low in fat and high in fiber , fruits , and vegetables does not influence the risk of recurrence of colorectal adenomas BACKGROUND The Lyon Diet Heart Study is a r and omized secondary prevention trial aim ed at testing whether a Mediterranean-type diet may reduce the rate of recurrence after a first myocardial infa rct ion . An intermediate analysis showed a striking protective effect after 27 months of follow-up . This report presents results of an extended follow-up ( with a mean of 46 months per patient ) and deals with the relationships of dietary patterns and traditional risk factors with recurrence . METHODS AND RESULTS Three composite outcomes ( COs ) combining either cardiac death and nonfatal myocardial infa rct ion ( CO 1 ) , or the preceding plus major secondary end points ( unstable angina , stroke , heart failure , pulmonary or peripheral embolism ) ( CO 2 ) , or the preceding plus minor events requiring hospital admission ( CO 3 ) were studied . In the Mediterranean diet group , CO 1 was reduced ( 14 events versus 44 in the prudent Western-type diet group , P=0.0001 ) , as were CO 2 ( 27 events versus 90 , P=0.0001 ) and CO 3 ( 95 events versus 180 , P=0 . 0002 ) . Adjusted risk ratios ranged from 0.28 to 0.53 . Among the traditional risk factors , total cholesterol ( 1 mmol/L being associated with an increased risk of 18 % to 28 % ) , systolic blood pressure ( 1 mm Hg being associated with an increased risk of 1 % to 2 % ) , leukocyte count ( adjusted risk ratios ranging from 1.64 to 2.86 with count > 9x10(9)/L ) , female sex ( adjusted risk ratios , 0.27 to 0 . 46 ) , and aspirin use ( adjusted risk ratios , 0.59 to 0.82 ) were each significantly and independently associated with recurrence . CONCLUSIONS The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infa rct ion , confirming previous intermediate analyses . Major traditional risk factors , such as high blood cholesterol and blood pressure , were shown to be independent and joint predictors of recurrence , indicating that the Mediterranean dietary pattern did not alter , at least qualitatively , the usual relationships between major risk factors and recurrence . Thus , a comprehensive strategy to decrease cardiovascular morbidity and mortality should include primarily a cardioprotective diet . It should be associated with other ( pharmacological ? ) means aim ed at reducing modifiable risk factors . Further trials combining the 2 approaches are warranted BACKGROUND Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease . We aim ed to test the hypothesis that long-term use of eicosapentaenoic acid ( EPA ) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish . METHODS 18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999 . Patients were r and omly assigned to receive either 1800 mg of EPA daily with statin ( EPA group ; n=9326 ) or statin only ( controls ; n=9319 ) with a 5-year follow-up . The primary endpoint was any major coronary event , including sudden cardiac death , fatal and non-fatal myocardial infa rct ion , and other non-fatal events including unstable angina pectoris , angioplasty , stenting , or coronary artery bypass grafting . Analysis was by intention-to-treat . The study was registered at Clinical Trials.gov , number NCT00231738 . FINDINGS At mean follow-up of 4.6 years , we detected the primary endpoint in 262 ( 2.8 % ) patients in the EPA group and 324 ( 3.5 % ) in controls-a 19 % relative reduction in major coronary events ( p=0.011 ) . Post-treatment LDL cholesterol concentrations decreased 25 % , from 4.7 mmol/L in both groups . Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events . Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group . Sudden cardiac death and coronary death did not differ between groups . In patients with a history of coronary artery disease who were given EPA treatment , major coronary events were reduced by 19 % ( secondary prevention subgroup : 158 [ 8.7 % ] in the EPA group vs 197 [ 10.7 % ] in the control group ; p=0.048 ) . In patients with no history of coronary artery disease , EPA treatment reduced major coronary events by 18 % , but this finding was not significant ( 104 [ 1.4 % ] in the EPA group vs 127 [ 1.7 % ] in the control group ; p=0.132 ) . INTERPRETATION EPA is a promising treatment for prevention of major coronary events , and especially non-fatal coronary events , in Japanese hypercholesterolaemic patients BACKGROUND Recent studies indicate that depression plays an important role in the occurrence of cardiovascular diseases ( CVDs ) . The underlying mechanisms are not well understood . OBJECTIVE We investigated whether dietary intake of the n-3 fatty acids ( FAs ) eicosapentaenic acid and docosahexaenoic acid could explain the relation between depressive symptoms and cardiovascular mortality . DESIGN The Zutphen Elderly Study is a prospect i ve cohort study conducted in the Netherl and s. Depressive symptoms were measured in 1990 with the Zung Self-rating Depression Scale in 332 men aged 70 - 90 y and free from CVD and diabetes . Dietary factors were assessed with a cross-check dietary history method in 1990 . Mortality data were collected between 1990 and 2000 . Logistic and Cox regression analyses were performed , with adjustment for demographics and CVD risk factors . RESULTS Compared with a low intake ( x : 21 mg/d ) , a high intake ( x : 407 mg/d ) of n-3 FAs was associated with fewer depressive symptoms [ odds ratio : 0.46 ; 95 % CI : 0.22 , 0.95 ; P for trend = 0.04 ] at baseline and no significant reduced risk of 10-y CVD mortality [ hazard ratio ( HR ) : 0.88 ; 95 % CI : 0.51 , 1.50 ] . The adjusted HR for an increase in depressive symptoms with 1 SD for CVD mortality was 1.28 ( 95 % CI : 1.03 , 1.57 ) and did not change after additional adjustment for the intake of n-3 FAs . CONCLUSION An average intake of approximately 400 mg n-3 FA/d may reduce the risk of depression . Our results , however , do not support the hypothesis that the intake of n-3 FAs explains the relation between depression and CVD BACKGROUND Results of epidemiologic studies and clinical trials indicate that moderate doses of n-3 fatty acids reduce the risk of cardiovascular disease and may improve prognosis . OBJECTIVE The objective was to evaluate the effect of a high-dose ethylester concentrate of n-3 fatty acids administered early after an acute myocardial infa rct ion ( MI ) on subsequent cardiac events and serum lipids . DESIGN Three hundred patients with acute MI were r and omly assigned to a daily dose of either 4 g highly concentrated n-3 fatty acids or corn oil , administered in a double-blind manner over 12 - 24 mo . Median follow-up time was 1.5 y. Clinical follow-up , including the drawing of blood sample s , was performed after 6 wk of treatment and later at 0.5-year intervals . RESULTS Forty-two ( 28 % ) patients in the n-3 group and 36 ( 24 % ) in the corn oil group experienced at least one cardiac event ( cardiac death , resuscitation , recurrent MI , or unstable angina ) . No significant difference in prognosis was observed between groups for single or combined cardiac events . Total cholesterol concentrations decreased in both groups , with no significant intergroup differences . On average , the monthly increase in HDL cholesterol was 1.11 % in the n-3 group and 0.55 % in the corn oil group ( P = 0.0016 ) . Triacylglycerol concentrations decreased by 1.30%/mo in the n-3 group , whereas they increased by 0.35%/mo in the corn oil group ( P < 0.0001 ) . CONCLUSION No clinical benefit of a high-dose concentrate of n-3 fatty acids compared with corn oil was found despite a favorable effect on serum lipids BACKGROUND AND AIMS epidemiological studies suggest polyunsaturated fatty Output:	There was no evidence that the observational studies pre date d RCTs in the translational process in either example . In the two examples , citation network characteristics do not predict concordance in the results of observational studies and RCTs
MS21690	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE This study was carried out to evaluate the therapeutic effect of epidural steroid injection on pseudoclaudication in patients with lumbar degenerative spinal canal stenosis . DESIGN Fifty-three patients who complained of pseudoclaudication of less than 20 m in walking distance were r and omly divided into three groups . Group 1 ( n = 16 ) underwent epidural injection with 8 ml of saline . Group 2 ( n = 18 ) underwent epidural block with 8 ml of 1 % mepivacaine . Group 3 ( n = 19 ) underwent epidural block with a combination of 8 ml of 1 % mepivacaine and 40 mg of methylprednisolone . The criteria of evaluation were as follows : excellent effect , > 100 m in walking distance ; good effect , 20 - 100 m in walking distance ; poor effect , < 20 m in walking distance . RESULTS In group 1 , the numbers of patients who showed a good effect were two ( 12.5 % ) after 1 week , one ( 6.5 % ) after 1 month , and one ( 6.5 % ) after 3 months . In group 2 , the numbers of patients who showed a good or excellent result were 10 ( 55.5 % ) after 1 week , three ( 16.7 % ) after 1 month , and one ( 5.6 % ) after 3 months . In group 3 , the numbers of patients who showed a good or excellent result were 12 ( 63.2 % ) after 1 week , three ( 15.8 % ) after 1 month , and one ( 5.3 % ) after 3 months . There was no significant difference in the effectiveness of treatment between group 2 and group 3 throughout the time course . CONCLUSION The results suggest that epidural steroid injection has no beneficial effect on the pseudoclaudication associated with spinal canal stenosis as compared with epidural block with a local anesthetic alone Study Design . A r and omized , controlled , double-blind trial . Objective . To assess the effectiveness of fluoroscopically directed caudal epidural injections in managing chronic low back and lower extremity pain in patients with disc herniation and radiculitis with local anesthetic with or without steroids . Summary of Background Data . The available literature on the effectiveness of epidural injections in managing chronic low back pain secondary to disc herniation is highly variable . Methods . One hundred twenty patients suffering with low back and lower extremity pain with disc herniation and radiculitis were r and omized to one of the two groups : group I received caudal epidural injections with an injection of local anesthetic , lidocaine 0.5 % , 10 mL ; group II patients received caudal epidural injections with 0.5 % lidocaine , 9 mL , mixed with 1 mL of steroid . The Numeric Rating Scale ( NRS ) , the Oswestry Disability Index 2.0 ( ODI ) , employment status , and opioid intake were utilized with assessment at 3 , 6 , and 12 months posttreatment . Results . The percentage of patients with significant pain relief of 50 % or greater and /or improvement in functional status with 50 % or more reduction in ODI scores was seen in 70 % and 67 % in group I and 77 % and 75 % in group II with average procedures per year of 3.8 ± 1.4 in group I and 3.6 + 1.1 in group II . However , the relief with first and second procedures was significantly higher in the steroid group . The number of injections performed was also higher in local anesthetic group even though overall relief was without any significant difference among the groups . There was no difference among the patients receiving steroids . Conclusion . Caudal epidural injection with local anesthetic with or without steroids might be effective in patients with disc herniation or radiculitis . The present evidence illustrates potential superiority of steroids compared with local anesthetic at 1-year follow-up Objective : To determine the efficacy of epidural corticosteroid injections for sciatica . Methods : Three epidural injections ( two day intervals ) of 2 ml prednisolone acetate ( 50 mg ) or 2 ml isotonic saline were administered to patients with sciatica presumably due to a disk herniation lasting 15–180 days . Self evaluation was the main judgment criterion at day 20 . Patients who recovered or showed marked improvement were considered as success . Pain measured by VAS , the SLR test , Schober ’s test , Dallas pain question naire , and the Rol and -Morris index were evaluated at days 0 , 5 , 20 , and 35 . Only analgesics were authorised , patients requiring non-steroidal anti-inflammatory drugs ( NSAIDs ) before day 20 were considered as failure . Results : 42 patients were included in the control group ( CG ) , 43 in the steroid group ( SG ) . On an intention to treat analysis 15/42 ( 36 % ) in the CG and 22/43 ( 51 % ) in the SG ( p=0.15 ) were considered as success ( difference 15.5 % , 95 % CI ( −5.4 to 36.3 ) ) . Among the 48 failures , 14 patients ( 6 CG , 8 SG ) required NSAIDs , 3 ( 2 CG , 1 SG ) required surgery , and 7 ( 3 CG , 4 SG ) other treatments . On analysis according to protocol , in 74 remaining patients 12/35 ( 34 % ) in the CG and 22/39 ( 56 % ) in the SG ( p=0.057 ) were considered as success ( difference 22.1 % , 95 % CI ( 0.0 to 44.2 ) ) . For all secondary end points intragroup improvement with time was significant , but intergroup differences were not . Conclusion : The efficacy of isotonic saline administered epidurally for sciatica can not be excluded , but epidural steroid injections provide no additional improvement BACKGROUND Epidural injections ( EI ) are the most commonly performed minimally invasive intervention to manage chronic low back pain ( CLBP ) with lumbosacral radicular pain ( LRP ) . Local anesthetic ( LA ) and /or steroids are frequently used injectates for EI and are reported with variable effectiveness . The majority of earlier studies have used either caudal , transforaminal ( TF ) , or undefined interlaminar approaches for EI . The parasaggital interlaminar ( PIL ) approach route is reported to have good ventral epidural spread and comparable effectiveness to the TF route . However , there is a lack of head-to-head comparative effectiveness research of LA with or without steroid for managing CLBP with LRP using a PIL approach . OBJECTIVE To compare the effectiveness of EI of LA alone and LA with steroid using a PIL approach for managing CLBP with LRP . STUDY DESIGN R and omized , double blind , active control one year follow-up study . SETTING Interventional pain management clinic in a tertiary care center in India . METHODS Sixty-nine patients were r and omized to receive fluoroscopic guided EI of either 8 mL of 0.5 % lidocaine ( group L , n = 34 ) or 6 mL of 0.5 % lidocaine mixed with 80 mg ( 2 mL ) of methylprednisolone acetate ( group LS , n = 35 ) . Patients were evaluated for pain intensity using 0 - 10 numerical rating scale ( NRS ) and functional disability using Modified Oswestry Disability Question naire ( MODQ ) at baseline ; and 2 weeks , one , 2 , 3 , 6 , 9 , and 12 months after injection . Patients with inefficacy with the initial injection or response deterioration received an additional injection of the same injectate and dose . Patients were evaluated for achieving effective pain relief ( EPR , i.e. , ≥ 50 % from baseline ) , overall NRS and MODQ , number of injections , and presence of ventral and perineural spread over one year follow-up . Primary outcome was proportion of patients achieving EPR at 3 months . RESULTS A significantly higher proportion of patients achieved EPR at 3 months in group LS [ 30 ( 86 % , 90 % CI 73 % - 93 % ) ] as compared to group L [ 17 ( 50 % , 90 % CI 36 % - 64 % ) ] ( P = 0.02 ) . Similar results were obtained at 6 , 9 , and 12 months , respectively . The probability of achieving EPR was significantly higher in group LS at various time-points during the one year follow-up as compared to group L ( P = 0.01 ) A significant reduction in NRS and improvement in MODQ were observed at all time-points post-intervention compared to baseline ( P < 0.001 ) in both groups . NRS and MODQ scores were significantly lower in group LS as compared to group L at all time intervals post baseline . On average patients in group L received 2.0 ( 0.85 ) and group LS received 1.7 ( 0.71 ) injections annually ( P = 0.07 ) . Ventral epidural spread was comparable in both groups ( 97 % ) . No major complications were encountered in either group ; however , intravascular spread of contrast was noted during 2 injections ( one in each group ) requiring relocation . LIMITATIONS A single center study , lack of documentation of adjuvant therapies like individual analgesic medication , and lack of placebo group . CONCLUSIONS Using a PIL approach and the addition of steroid to LA for EI may provide superior effectiveness in terms of extent and duration of pain relief for managing CLBP with unilateral LRP , even though , local anesthetic alone also was effective . TRIAL REGISTRATION Two controlled studies for a new epidural , perineural , singleshot , selective nerve root injection with a double-needle approach to the anterior epidural space of the lumbar spinal canal are presented . The results were analysed to determine the effectiveness of the new epidural perineural injection technique . The trial comprised two controlled studies on 182 patients . One study compared prospect ively r and omized results of patients with lumbar radicular syndromes who received epidural perineural injections ( n = 47 ) , conventional posterior epidural injections ( n = 40 ) and , as a control group , paravertebral local anaesthetic ( n = 46 ) . A second , prospect i ve , double-blind study compared the effect of epidural perineural injections with triamcinolone ( n = 24 ) and pure saline ( n = 25 ) . Epidural perineural injections were more effective than conventional posterior epidural injections . Both epidural groups had better results than the paravertebral local injection group . Epidural perineural injections with steroids ( 10 mg triamcinolone ) were more effective than saline alone . A systemic steroid effect was excluded by additional intramuscular steroid injections in the saline group . There were no severe complications or side effects in any of the three groups . The studies concluded that single-shot epidural perineural injection is effective in the treatment of lumbar radicular pain . It is a “ one drop only ” therapy to the source of pain Abstract This analysis of the lumbar epidural steroid injections for spinal stenosis multicenter r and omized controlled trial data identifies the degree of and risk factors for cortisol suppression after epidural steroid injections in older adults with spinal stenosis . Four hundred patients aged 50 years and older with back or leg pain and central lumbar spinal stenosis completed baseline demographic and psychosocial measures . Morning serum cortisol levels were measured at baseline and 3 weeks after initial injection . Patients were r and omized to receive epidural injections of either local anesthetic with corticosteroid ( n = 200 ) or local anesthetic only ( n = 200 ) . The specific corticosteroid was chosen at the treating physician 's discretion ( methylprednisolone , betamethasone , triamcinolone , or dexamethasone ) . Thirty-two patients ( 20.3 % ) treated with corticosteroid experienced cortisol reduction at 3 weeks of > 50 % compared with 10 patients ( 6.7 % ) treated with lidocaine only ( adjusted treatment effect = 3.5 , 95 % confidence interval : 1.6 - 7.9 , P = 0.002 ) . The effect on 3-week cortisol changes did not differ by demographic or patient-level characteristics . Those treated with methylprednisolone or triamcinolone had an average 3-week cortisol reduction of 41.0 % ( P = 0.005 ) and 41.6 % ( P < 0.001 ) from baseline , respectively , whereas patients treated with betamethasone or dexamethasone were not significantly different than comparable patients in the lidocaine arm . The higher rates of cortisol suppression at 3 weeks in those receiving epidural corticosteroid injections , particularly with longer-acting insoluble corticosteroid formulations , are consistent with sustained systemic absorption of corticosteroid Background Transforaminal epidural injections with steroids ( TESI ) are used increasingly for patients with sciatica . However there is much debate about their safety and effectiveness . It is important to identify patients that benefit most from TESI and only few trials have yet evaluated the effects in patients with acute sciatica . Methods We describe a prospect i ve , r and omized controlled trial ( RCT ) , with the aim to evaluate the hypothesis that TESI plus Levobupivacaine ( TESI-plus ) added to oral pain medication is more effective compared to pain medication alone or compared to transforaminal injection with a local Output:	AUTHORS ' CONCLUSIONS This study found that epidural corticosteroid injections probably slightly reduced leg pain and disability at short-term follow-up in people with lumbosacral radicular pain . In addition , no minor or major adverse events were reported at short-term follow-up after epidural corticosteroid injections or placebo injection . Although the current review identified additional clinical trials , the available evidence still provides only limited support for the use of epidural corticosteroid injections in people with lumbosacral radicular pain as the treatment effects are small , mainly evident at short-term follow-up and may not be considered clinical ly important by patients and clinicians ( i.e. mean difference lower than 10 % ) .
MS21691	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Since the 1950s carotid endarterectomy has been performed in patients with symptomatic carotid artery stenosis , based on suggestive but inconclusive evidence for its effectiveness . Only during the last 5 years have r and omized studies clarified the indications for surgery . In preparing this report , panel members used the same rules of evidence used in the previous report1 2 ( Table ⇓ ) . View this table : Table 1 . Levels of Evidence and Grading of Recommendations Few studies have analyzed control of risk factors in a r and omized , prospect i ve manner following carotid endarterectomy . However , a wealth of data are available regarding the general relationship between risk factor control and stroke risk . These data provide some guidance for the care of endarterectomy patients . # # # Hypertension Hypertension is the most powerful , prevalent , and treatable risk factor for stroke.3 Both systolic and diastolic blood pressure are independently related to stroke incidence . Isolated systolic hypertension , which is common in the elderly , also considerably increases risk of stroke . Reduction of elevated blood pressure significantly lowers risk of stroke . Meta-analyses of r and omized trials found that an average reduction in diastolic blood pressure of 6 mm Hg produces a 42 % reduction in stroke incidence.3 4 Treatment of isolated systolic hypertension in people older than 60 years also reduces stroke incidence by 36 % without an excessive number of side effects such as depression or dementia.5 Long-term care of patients after endarterectomy should include careful control of hypertension ( Grade A recommendation for treatment of hypertension in general ; Grade C recommendation for postendarterectomy care ) . Perioperative treatment of hypertension after carotid endarterectomy represents a special situation . Poor control of blood pressure after endarterectomy increases risk of cerebral hyperperfusion syndrome.6 7 8 9 This complication is characterized by unilateral headache , seizures , and occasionally altered mental status or focal neurological signs . Neuroimaging may show intracerebral hemorrhages10 11 12 or white OBJECTIVE To determine whether the addition of carotid endarterectomy to aggressive medical management can reduce the incidence of cerebral infa rct ion in patients with asymptomatic carotid artery stenosis . DESIGN Prospect i ve , r and omized , multicenter trial . SETTING Thirty-nine clinical sites across the United States and Canada . PATIENTS Between December 1987 and December 1993 , a total of 1662 patients with asymptomatic carotid artery stenosis of 60 % or greater reduction in diameter were r and omized ; follow-up data are available on 1659 . At baseline , recognized risk factors for stroke were similar between the two treatment groups . INTERVENTION Daily aspirin administration and medical risk factor management for all patients ; carotid endarterectomy for patients r and omized to receive surgery . MAIN OUTCOME MEASURES Initially , transient ischemic attack or cerebral infa rct ion occurring in the distribution of the study artery and any transient ischemic attack , stroke , or death occurring in the perioperative period . In March 1993 , the primary outcome measures were changed to cerebral infa rct ion occurring in the distribution of the study artery or any stroke or death occurring in the perioperative period . RESULTS After a median follow-up of 2.7 years , with 4657 patient-years of observation , the aggregate risk over 5 years for ipsilateral stroke and any perioperative stroke or death was estimated to be 5.1 % for surgical patients and 11.0 % for patients treated medically ( aggregate risk reduction of 53 % [ 95 % confidence interval , 22 % to 72 % ] ) . CONCLUSION Patients with asymptomatic carotid artery stenosis of 60 % or greater reduction in diameter and whose general health makes them good c and i date s for elective surgery will have a reduced 5-year risk of ipsilateral stroke if carotid endarterectomy performed with less than 3 % perioperative morbidity and mortality is added to aggressive management of modifiable risk factors BACKGROUND The efficacy of carotid endarterectomy in patients with asymptomatic carotid stenosis has not been confirmed in r and omized clinical trials , despite the widespread use of operative intervention in such patients . METHODS We conducted a multicenter clinical trial at 11 Veterans Affairs medical centers to determine the effect of carotid endarterectomy on the combined incidence of transient ischemic attack , transient monocular blindness , and stroke . We studied 444 men with asymptomatic carotid stenosis shown arteriographically to reduce the diameter of the arterial lumen by 50 percent or more . The patients were r and omly assigned to optimal medical treatment including antiplatelet medication ( aspirin ) plus carotid endarterectomy ( the surgical group ; 211 patients ) or optimal medical treatment alone ( the medical group ; 233 patients ) . All the patients at each center were followed independently by a vascular surgeon and a neurologist for a mean of 47.9 months . RESULTS The combined incidence of ipsilateral neurologic events was 8.0 percent in the surgical group and 20.6 percent in the medical group ( P < 0.001 ) , giving a relative risk ( for the surgical group vs. the medical group ) of 0.38 ( 95 percent confidence interval , 0.22 to 0.67 ) . The incidence of ipsilateral stroke alone was 4.7 percent in the surgical group and 9.4 percent in the medical group . An analysis of stroke and death combined within the first 30 postoperative days showed no significant differences . Nor were there significant differences between groups in an analysis of all strokes and deaths ( surgical , 41.2 percent ; medical , 44.2 percent ; relative risk , 0.92 ; 95 percent confidence interval , 0.69 to 1.22 ) . Overall mortality , including postoperative deaths , was primarily due to coronary atherosclerosis . CONCLUSIONS Carotid endarterectomy reduced the overall incidence of ipsilateral neurologic events in a selected group of male patients with asymptomatic carotid stenosis . We did not find a significant influence of carotid endarterectomy on the combined incidence of stroke and death , but because of the size of our sample , a modest effect could not be excluded BACKGROUND Percutaneous transluminal angioplasty and stenting ( endovascular treatment ) can be used to treat carotid stenosis , but risks and benefits are uncertain . We therefore compared endovascular treatment with conventional carotid surgery . METHODS In a multicentre clinical trial , we r and omly assigned 504 patients with carotid stenosis to endovascular treatment ( n=251 ) or carotid endarterectomy ( n=253 ) . For endovascular patients treated successfully , we used stents in 55 ( 26 % ) and balloon angioplasty alone in 158 ( 74 % ) . An independent neurologist followed up patients . Analysis was by intention to treat . FINDINGS The rates of major outcome events within 30 days of first treatment did not differ significantly between endovascular treatment and surgery ( 6.4 % vs 5.9 % , respectively , for disabling stroke or death ; 10.0 % vs 9.9 % for any stroke lasting more than 7 days , or death ) . Cranial neuropathy was reported in 22 ( 8.7 % ) surgery patients , but not after endovascular treatment ( p<0.0001 ) . Major groin or neck haematoma occurred less often after endovascular treatment than after surgery ( three [ 1.2 % ] vs 17 [ 6.7 % ] , p<0.0015 ) . At 1 year after treatment , severe ( 70 - 99 % ) ipsilateral carotid stenosis was more usual after endovascular treatment ( 25 [ 14 % ] vs seven [ 4 % ] , p<0.001 ) . However , no substantial difference in the rate of ipsilateral stroke was noted with survival analysis up to 3 years after r and omisation ( adjusted hazard ratio=1.04 , 95 % CI 0.63 - 1.70 , p=0.9 ) . INTERPRETATION Endovascular treatment had similar major risks and effectiveness at prevention of stroke during 3 years compared with carotid surgery , but with wide CIs . Endovascular treatment had the advantage of avoiding minor complications OBJECTIVE Current clinical trials evaluating carotid stenting have focused on high-risk patients and may not reflect the broad population of patients with carotid stenosis who undergo treatment to prevent stroke . The Carotid Revascularization Using Endarterectomy or Stenting Systems ( CaRESS ) phase I study is a multicenter , prospect i ve , nonr and omized trial design ed to address the question of whether carotid stenting ( CAS ) with cerebral protection is comparable to carotid endarterectomy ( CEA ) in patients with symptomatic and asymptomatic carotid stenosis . METHODS Patients with symptomatic ( with > 50 % stenosis ) or asymptomatic ( with > 75 % stenosis ) carotid stenosis were entered into the study in a 2:1 ratio of carotid stent and GuardWire Plus distal protection device . This unique trial model was developed through collaboration with the International Society of Endovascular Specialists , the Food and Drug Administration , the Centers for Medicare and Medicaid Services , the National Institutes of Health , and industry representatives . The primary end points included death and stroke at 30 days and a composite 1-year end point of death , stroke , or myocardial infa rct ion ( MI ) from 0 to 30 days and death or stroke from 31 days to 1 year . The secondary end points included residual stenosis , restenosis , repeat angiography , and carotid revascularization at 30 days and 1 year and quality -of-life changes at 1 year . RESULTS A total of 397 patients ( 254 CEA and 143 CAS ) were enrolled in the study : 32 % were symptomatic and 68 % were asymptomatic . There were no significant differences in patient characteristics , symptoms , or surgical risk profiles between groups at baseline . Kaplan-Meier analysis revealed no significant differences in combined death/stroke rates at 30 days ( 3.6 % CEA vs 2.1 % CAS ) or at 1 year ( 13.6 % CEA vs 10.0 % CAS ) . Similarly , there was no significant difference in the combined end point of death , stroke , or MI at 30 days ( 4.4 % CEA vs 2.1 % CAS ) or at 1 year ( 14.3 % CEA vs 10.9 % CAS ) . There were no significant differences between CEA and CAS in the secondary end points of residual stenosis ( 0 % CEA vs 0.9 % CAS ) , restenosis ( 3.6 % CEA vs 6.3 % CAS ) , repeat angiography ( 2.1 % CEA vs 3.6 % CAS ) , carotid revascularization ( 1.0 % CEA vs 1.8 % CAS ) , or change in quality of life ( -1.56 points CEA vs -4.22 points CAS ) . CONCLUSIONS The CaRESS phase I study suggests that the 30-day and 1-year risk of death , stroke , or MI with CAS is equivalent to that with CEA in symptomatic and asymptomatic patients with carotid stenosis BACKGROUND Among patients with substantial carotid artery narrowing but no recent neurological symptom ( stroke or transient ischaemia ) , the balance of surgical risks and long-term benefits from carotid endarterectomy ( CEA ) was unclear . METHODS During 1993 - 2003 , 3120 asymptomatic patients with substantial carotid narrowing were r and omised equally between immediate CEA ( half got CEA by 1 month , 88 % by 1 year ) and indefinite deferral of any CEA ( only 4 % per year got CEA ) and were followed for up to 5 years ( mean 3.4 years ) . Kaplan-Meier analyses of 5-year risks are by allocated treatment . FINDINGS The risk of stroke or death within 30 days of CEA was 3.1 % ( 95 % CI 2.3 - 4.1 ) . Comparing all patients allocated immediate CEA versus all allocated deferral , but excluding such perioperative events , the 5-year stroke risks were 3.8 % versus 11 % ( gain 7.2 % [ 95 % CI 5.0 - 9.4 ] , p<0.0001 ) . This gain chiefly involved carotid territory ischaemic strokes ( 2.7 % vs 9.5 % ; gain 6.8 % [ 4.8 - 8.8 ] , p<0.0001 ) , of which half were disabling or fatal ( 1.6 % vs 5.3 % ; gain 3.7 % [ 2.1 - 5.2 ] , p<0.0001 ) , as were half the perioperative strokes . Combining the perioperative events and the non-perioperative strokes , net 5-year risks were 6.4 % versus 11.8 % for all strokes ( net gain 5.4 % [ 3.0 - 7.8 ] , p<0.0001 ) , 3.5 % versus 6.1 % for fatal or disabling strokes ( net gain 2.5 % [ 0.8 - 4.3 ] , p=0.004 ) , and 2.1 % versus 4.2 % just for fatal stro Output:	Meta- analysis of trials to date shows CAS is associated with higher 30-day risk of stroke/death compared with CEA . Thus , for the patient at average surgical risk , the role of CAS is unproven , especially for symptomatic patients . And for the patient at high surgical risk , the role of any intervention is uncertain in the setting of competing comorbidities .
MS21692	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background The role of laparoscopic resection ( LR ) in the management of extraperitoneal rectal cancer still is unclear . This study aim ed to compare perioperative and long-term results of laparoscopic and open resection ( OR ) for low and midrectal cancer . Methods A prospect i ve nonr and omized trial comparing patients su bmi tted to OR or LR for low and midrectal cancer at a single institution was conducted . Results The study included 191 consecutive patients : 98 patients who underwent LR and 93 who underwent OR . The mean follow-up period was 46.3 months for LR and 49.7 months for OR . The conversion rate for LR was 18.4 % . With the use of LR , the mean time for complete patient mobilization was shorter ( 1.7 vs 3.3 days ; p < 0.001 ) and patients were earlier in passing flatus ( 2.6 vs 3.9 days ; p < 0.001 ) and stools ( 3.8 vs 4.7 days ; p < 0.01 ) , and in resuming oral intake ( 3.4 vs 4.8 days ; p < 0.001 ) . The mean hospital stay was shorter for LR , but the difference did not reach significance ( 11.4 vs 13 days ) . Morbidity and mortality rates were similar : LR ( 24.4 % and 1 % ) and OR ( 23.6 % and 2.2 % ) . Laparoscopic patients presented a higher rate of anastomotic fistulas ( 13.5 % vs 5.1 % ) and reoperations ( 6.1 % vs 3.2 % ) but the difference was statistically nonsignificant . Laparoscopic resection presented a significantly lower local recurrence rate ( 3.2 % vs 12.6 % ; p < 0.05 ) . The cumulative survival and disease-free rates at 5 years were , respectively , 80 % and 65.4 % after LR and 68.9 % and 58.9 % after OR ( nonsignificant difference ) . Stage-by-stage comparison showed prolonged cumulative survival for stages III and IV cancer in LR ( 82.5 % vs 40.5 % ; p = 0.006 and 15.8 % vs 0 % ; p = 0.013 , respectively ) and a reduced rate of cancer-related death for stage III in LR ( 11.4 % vs 51.9 % ; p = 0.001 ) . Conclusions As compared with conventional open surgery , LR for low and midrectal cancer is characterized by a faster recovery and similar overall morbidity ( but a higher rate of anastomotic leakages ) , and does not present any adverse oncologic effect Purpose Laparoscopic surgery of colon cancer has been accepted to be oncologically adequate compared with open resection . However , the situation in rectal cancer remains unclear , because anatomy and complex surgical procedures might specifically influence the long-term outcome . This study was design ed to analyze perioperative and long-term outcome of patients with rectal cancer after laparoscopic vs. open access surgery . Methods A total of 389 patients ( 1998–2005 ) were prospect ively analyzed ; 114 patients had laparoscopic beginning , and 25 patients had conversion and were separately analyzed . Eighty-nine patients remained in the laparoscopic group and 275 had open access surgery . Results Both groups were comparable regarding age , gender , tumor localization , stage , and complications . Differences were found in harvested lymph nodes ( laparoscopic 13.5/open access 16.9 ; P = 0.001 ) and hospitalization ( 15.1/18.7 days ; P = 0.037 ) . Local recurrence rate and metachronous metastasis were comparable . In patients with deep anterior resection with total mesenteric excision , favorable long-term survival in the laparoscopic group was found ( P = 0.035 , log-rank ) . Conclusions Minimally invasive surgery is equivalent in the treatment of rectal cancer and shows advantages of shorter hospitalization and faster recovery . Especially in patients with low rectal cancer , minimally invasive surgery with exact preparation of the total mesenteric excision seems to be favorable compared with open access surgery Purpose This study was design ed to evaluate the impact of laparoscopic rectal resection on short-term postoperative morbidity and costs . Methods A total of 168 patients with rectal cancer were r and omly assigned to laparoscopic ( n = 83 ) or open ( n = 85 ) resection . Outcome parameters were : postoperative morbidity , length of hospital stay , quality of life , long-term survival , and local recurrences . The mean follow-up period was 53.6 months . Cost-benefit analysis was based on hospital costs . Results Operative time was 53 minutes longer in the laparoscopic group ( P < 0.0001 ) . Postoperative morbidity rate was 28.9 percent in the laparoscopic vs. 40 percent in the open group ( P = 0.18 ) . The mean length of hospital stay was 10 ( 4.9 ) days in the laparoscopic group and 13.6 ( 10 ) days in the open group ( P = 0.004 ) . Local recurrence rate and five-year survival were similar in both groups ; however , the limited number of patients does not allow firm conclusions . Quality of life was better in the laparoscopic group only in the first year after surgery ( P < 0.0001 ) . The additional charge in the laparoscopic group was $ 1,748 per patient r and omized ( $ 1,194 the result of surgical instruments and $ 554 the result of longer operative time ) . The saving in the laparoscopic group was $ 1,396 per patient r and omized ( $ 647 the result of shorter length of hospital stay and $ 749 the result of the lower cost of postoperative complications ) . The net balance result ed in $ 351 extra cost per patient r and omly allocated to the laparoscopic group . Conclusions Short-term postoperative morbidity was similar in the two groups . Laparoscopic resection reduced length of hospital stay , improved first-year quality of life , and slightly increased hospital costs BACKGROUND The safety and short-term benefits of laparoscopic colectomy for cancer remain debatable . The multicentre COLOR ( COlon cancer Laparoscopic or Open Resection ) trial was done to assess the safety and benefit of laparoscopic resection compared with open resection for curative treatment of patients with cancer of the right or left colon . METHODS 627 patients were r and omly assigned to laparoscopic surgery and 621 patients to open surgery . The primary endpoint was cancer-free survival 3 years after surgery . Secondary outcomes were short-term morbidity and mortality , number of positive resection margins , local recurrence , port-site or wound-site recurrence , metastasis , overall survival , and blood loss during surgery . Analysis was by intention to treat . Here , clinical characteristics , operative findings , and postoperative outcome are reported . FINDINGS Patients assigned laparoscopic resection had less blood loss compared with those assigned open resection ( median 100 mL [ range 0 - 2700 ] vs 175 mL [ 0 - 2000 ] , p<0.0001 ) , although laparoscopic surgery lasted 30 min longer than did open surgery ( p<0.0001 ) . Conversion to open surgery was needed for 91 ( 17 % ) patients undergoing the laparoscopic procedure . Radicality of resection as assessed by number of removed lymph nodes and length of resected oral and aboral bowel did not differ between groups . Laparoscopic colectomy was associated with earlier recovery of bowel function ( p<0.0001 ) , need for fewer analgesics , and with a shorter hospital stay ( p<0.0001 ) compared with open colectomy . Morbidity and mortality 28 days after colectomy did not differ between groups . INTERPRETATION Laparoscopic surgery can be used for safe and radical resection of cancer in the right , left , and sigmoid colon Abstract . Previous analyses of non- prospect ively r and omized trials have suggested that early oral postoperative feeding might be a benefit unique to laparoscopic surgery . However , some authors have indicated that early feeding can be tolerated by the majority of patients after elective open surgery . Aim : This prospect i ve r and omized study was undertaken to assess whether the time prior to oral intake of food after laparoscopy-assisted surgery is shorter than that after st and ard laparotomy . Methods : This trial included 40 patients who were divided r and omly into two groups before operation . Group I included 20 patients ( mean age , 52 years ; range , 15 – 77 years ) who underwent a laparoscopy-assisted colon or rectal procedure ( LAP ) . Group II consisted of 20 patients ( mean age , 56 years , range , 41 – 74 years ) who underwent surgery with a st and ard midline incision ( SMI ) . On the evening after surgery , patients were allowed clear liquids ab libitum . This regimen was continued until the first postoperative day at which time they could elect to start eating a regular diet . If a patient had two episodes of vomiting , a nasogastric tube was inserted . Results : Five laparoscopic procedures were converted to SMI because of adhesions ( 25 % ) and an equal number of patients was excluded from the group that was treated in the traditional manner . Therefore , only 30 patients were included in the analysis . There were no deaths in this trial . Complications appeared in four of the patients in the LAP group and in two of the patients in the SMI group ( no significant difference ) . There were no statistically significant differences between the two groups in terms of the ability to tolerate the early oral intake of food , in the frequency of vomiting or in the incidence of insertion of a nasogastric tube . The time to the first bowel movement was 5.4 days in LAP and 5.5 days in SMI , and the difference was not significant . Conclusion : This study invali date s the cl aim by laparoscopic surgeons that earlier oral intake of food is tolerated by their patients than by patients who undergo st and ard procedures .Résumé . Des études r and omisées non prospect ives ont suggéré que la reprise précoce de l'alimentation orale peut être un bénéfice particulier à la chirurgie laparoscopique . Certains auteurs ont indiqué que la reprise précoce de l'alimentation orale peut être bien tolérée par la plupart des patients après chirurgie élective ouverte . Cette étude prospect i ve r and omisée a été entreprise pour déterminer si la reprise orale de l'alimentation après chirurgie laparoscopique peut être plus précoce qu'après une laparotomie st and ard . Quarante patients ont été inclus dans cette étude et ont été divisés de manière r and omisée en deux groupes avant chirurgie . Le groupe 1 comporte 20 patients ( 15 à 77 ans , moyenne d'âge 52 ans ) qui ont subi une résection colique ou rectale laparoscopique ( LAP ) . Le groupe II comporte 20 patients ( 41 à 74 ans , moyenne d'âge 56 ans ) qui ont subi une chirurgie par une incision médiane st and ard ( SMI ) . Le soir de l'intervention chirurgicale , les patients ont été autorisés à boire librement . Ce régime a été continué le premier jour postopératoire à partir duquel les patients pouvaient débuter une alimentation normale . Si un patient présente deux épisodes de vomissements , une sonde naso-gastrique a été mise en place . Cinq interventions laparaoscopiques ont dûêtre converties en chirurgie ouverte en raison d'adhérences ( 25 % ) et un nombre égal de patients ont été exclus du groupe qui a été traité de manière traditionelle . En conséquence , 30 patients ont été inclus dans l'analyse . Aucun décès n'est à déplorer . Quatre complications sont survenues chez des patients du groupe laparoscopique et deux dans le collectif des patients ayant subi un chirurgie ouverte ( pas de différence statistique significative ) . Il n'y a pas de différence statistique significative entre les deux groupes en ce qui concerne la tolérance à la reprise orale de l'alimentation , à la fréquence des vomissements ou à la nécessité de réinsérer un tube naso-gastrique . La première exonération est survenue au 5.4 jour dans le groupe laparoscopique et au 5,5 jour dans le groupe de chirurgie ouverte sans que la différence ne soit significative . En conclusion : Cette étude infirme l'idée que la chirurgie laparoscopique permet une reprise précoce et bien tolérée de l'alimentation en comparaison à la chirrugie ouverte AIM To evaluate the feasibility of laparoscopic resection of rectal carcinoma and to compare the short-term outcome of laparoscopic procedure with conventional open surgery for rectal cancer . METHODS Thirty-eight patients with rectal cancer were included in a prospect i ve non-r and omized study . The patients were assigned to laparoscopic ( n=18 ) or open ( n=18 ) colorectal resection . Case selection , surgical technique , and clinical and pathological results were review ed . RESULTS The operative time was longer in laparoscopic resection group ( LAP ) than in open resection group ( 189+/-18 min vs 146+/-22 min Output:	Conclusions On the basis of evidence of both r and omized and prospect i ve controlled series , mortality and morbidity RR , including subgroup analysis , were significantly lower after laparoscopic compared to open surgery
MS21693	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Milk thistle ( Silybum marianum ) extracts are widely used as a complementary and alternative treatment of various hepatic conditions and a host of other diseases/disorders . The active constituents of milk thistle supplements are believed to be the flavonolignans contained within the extracts . In vitro studies have suggested that some milk thistle components may significantly inhibit specific cytochrome P450 ( P450 ) enzymes . However , determining the potential for clinical ly significant drug interactions with milk thistle products has been complicated by inconsistencies between in vitro and in vivo study results . The aim of the present study was to determine the effect of a st and ardized milk thistle supplement on major P450 drug-metabolizing enzymes after a 14-day exposure period . CYP1A2 , CYP2C9 , CYP2D6 , and CYP3A4/5 activities were measured by simultaneously administering the four probe drugs , caffeine , tolbutamide , dextromethorphan , and midazolam , to nine healthy volunteers before and after exposure to a st and ardized milk thistle extract given thrice daily for 14 days . The three most abundant falvonolignans found in plasma , following exposure to milk thistle extracts , were silybin A , silybin B , and isosilybin B. The concentrations of these three major constituents were individually measured in study subjects as potential perpetrators . The peak concentrations and areas under the time-concentration curves of the four probe drugs were determined with the milk thistle administration . Exposure to milk thistle extract produced no significant influence on CYP1A2 , CYP2C9 , CYP2D6 , or CYP3A4/5 activities Objectives : Since grapefruit juice ( Gra ) inhibits hepatic P450 ( CYP3A4 ) , we studied its potential to enhance the effects of midazolam ( Mid ) and triazolam ( Trz ) , which are metabolized by the CYP3A4 isoenzyme . Methods : In Study I parallel groups of healthy students were given orally Mid 10 mg with water or grapefruit juice ( GraMid ) , two placebo groups receiving water or Gra . The effects of Mid were measured by psychomotor tests and by self-rating on visual analogue scales before and 30 and 90 min after intake . Study II was similar , but the post-treatment tests were at 45 and 90 min , and the active drugs used were 0.250 mg Trz , GraTrz , and Mid 10 mg . In the crossover Study III , 6 subjects took Mid 10 mg alone and with Gra ( GraMid ) and 750 mg erythromycin ( EryMid ) . Performance tests were made and blood was sample d before and 30 , 60 and 90 min after intake . Midazolam and its active metabolite α-OH-midazolam were assayed by gas chromatography ( GC ) and radioreceptor assay ( RRA ) . Results : In Study I , both Mid and GraMid impaired digit symbol substitution ( DSS ) , letter cancellation ( LC ) and flicker fusion ( CFF ) at 90 min . GraMid had more effect ( P < 0.05 ) than Mid on the DSS performance . Mid caused drowsiness at 30 and 90 min . Both Mid and GraMid caused clumsiness and a feeling of impaired performance at 90 min . In Study II , the active drugs impaired objective test performances ( DSS , LC , CFF ) at 90 min , without having a clear subjective effect . In Study III , Mid , EryMid and GraMid impaired performance in the DSS , LC and CFF tests . EryMid proved stronger than Mid and GraMid on DSS and LC tests at 30 min . Mean values of plasma midazolam ( and α-OH-midazolam ) at 30 , 60 , 90 and 120 min after Mid 10 mg were 68 ( 19 ) , 61 ( 19 ) , 43 ( 14 ) and 42 ( 12 ) μg⋅l−1 . The corresponding values after EryMid were 164 ( 14 ) , 137 ( 13 ) , 104(10 ) and 89(10 ) μg ⋅l−1 , and after GraMid 60 ( 12 ) , 69 ( 16 ) , 61 ( 15 ) and 57 ( 14 ) μg⋅l−1 . Conclusions : The grapefruit juice used did have any particular interaction with oral doses of 10 mg midazolam and 0.25 mg triazolam in healthy young subjects BACKGROUND Grapefruit juice ( GFJ ) enhances the systemic exposure of numerous CYP3A4 drug substrates , including felodipine , by inhibiting intestinal ( but not hepatic ) first-pass metabolism . Furanocoumarins have been identified as major CYP3A4 inhibitors contained in the juice , but their contribution to the GFJ effect in vivo remains unclear . OBJECTIVE To ascertain whether furanocoumarins mediate the GFJ-felodipine interaction , a furanocoumarin-free GFJ was created and tested against orange juice and the original GFJ with respect to the oral pharmacokinetics of felodipine . DESIGN With the use of food- grade solvents and absorption resins , furanocoumarins were removed ( approximately 99 % ) from whole GFJ , whereas other major ingredients ( flavonoids ) were retained . In an open , 3-way , r and omized crossover design , 18 healthy volunteers ingested felodipine ( 10 mg ) with 1 of the 3 juices ( 240 mL ) . Blood was collected over 24 h. At least 1 wk elapsed between juice treatments . RESULTS The median and range of the area under the curve and the maximum concentration of felodipine were significantly ( P < 0.001 ) greater with consumption of GFJ [ 110 ( range : 58 - 270 ) nmol . h/L and 21 ( 7.6 - 50 ) nmol/L , respectively ] than with that of orange juice [ 54 ( 29 - 150 ) nmol . h/L and 7.6 ( 3.4 - 13.9 ) nmol/L , respectively ] or furanocoumarin-free GFJ [ 48 ( 23 - 120 ) nmol . h/L and 8.3 ( 3.0 - 16.6 ) nmol/L , respectively ] . GFJ , orange juice , and furanocoumarin-free GFJ did not differ significantly ( P > 0.09 ) in median time to reach maximum plasma concentration [ 2.5 ( 1.5 - 6 ) , 2.8 ( 1.5 - 4 ) , and 2.5 ( 2 - 6 ) h , respectively ] or terminal half-life [ 6.6 ( 4.2 - 13.6 ) , 7.8 ( 4.4 - 13.2 ) , and 6.8 ( 2.6 - 14.4 ) h , respectively ] . CONCLUSION Furanocoumarins are the active ingredients in GFJ responsible for enhancing the systemic exposure of felodipine and probably other CYP3A4 substrates that undergo extensive intestinal first-pass metabolism Systemic clearance of intravenous ( IV ) alfentanil ( ALF ) is an in vivo probe for hepatic cytochrome P450 ( CYP ) 3A activity , miosis is a surrogate for plasma ALF concentrations , and IV ALF miosis is a noninvasive probe for hepatic CYP3A . This investigation characterized the bioavailability and first‐pass metabolism of oral ALF and tested the hypotheses that ( 1 ) first‐pass ALF clearance reflects first‐pass CYP3A activity , ( 2 ) miosis after oral ALF will reflect intestinal and hepatic CYP3A activity , and ( 3 ) miosis can approximate plasma concentration‐based pharmacokinetic measures for IV and oral ALF as a noninvasive in vivo probe for hepatic and first‐pass CYP3A activity and drug interactions . Results were compared with those for midazolam ( MDZ ) , an alternative CYP3A probe Consumption of typical quantities of grapefruit juice ( GFJ ) increases the oral bioavailability of several CYP3A4 substrates without affecting their elimination , consistent with selective inhibition of intestinal but not hepatic CYP3A4 . However , increases in the AUCs of CYP3A4 substrates recently associated with the consumption of large amounts of GFJ were similar to those observed with potent inhibitors of hepatic CYP3A4 . The current study compared the effects of consuming large quantities and more typical amounts of GFJ on the activity of hepatic and intestinal cytochrome P450 3A4 in vivo , employing the erythromycin breath test ( EBT ) and oral midazolam pharmacokinetics . This was a two-phase , r and omized , placebo-controlled crossover study , with each phase conducted with a separate panel of subjects . In Phase I , 8 male volunteers were r and omized to the order of receiving one glass ( 240 mL ) of water ( placebo ) or double-strength ( DS ) GFJ tid for 2 days and then 90 , 60 , and 30 minutes prior to administration of probe drugs on the 3rd day . In Phase II , 16 male volunteers were r and omized to the order of receiving one glass of ( 1 ) single-strength ( SS ) GFJ , ( 2 ) DS GFJ , and ( 3 ) water ( placebo ) . All treatments were administered in a fasted state . There was at least a 7-day washout period between treatments . Probe drugs , administered 30 minutes or 1 hour following each treatment in Phase I or II , respectively , consisted of oral midazolam ( 2 mg ) coadministered with IV [ 14 G N-methyl ] erythromycin ( 0.03 mg ) . The EBT was performed 20 minutes following erythromycin administration . Blood was collected during the 24 hours following probe drug administration for the analysis of midazolam pharmacokinetics . In Phase I , consumption of one glass of DS GFJ tid for 3 days increased the Cmax of midazolam 3-fold , the AUC 6-fold , and the t1/2 2-fold and decreased the amount of exhaled 14CO2 in all 8 subjects , with a mean decrease in EBT of 18 % . In Phase II , consumption of one glass of DS GFJ significantly increased the AUC and Cmax of midazolam approximately 2-fold without a significant effect on the t1/2 of midazolam or the EBT . The effects of consuming one glass of SS GFJ on midazolam pharmacokinetics and the EBT were not significantly different from those of one glass of DS GFJ . It was concluded that consumption of one glass of DS GFJ tid for 3 days significantly increased the AUC , Cmax , and t1/2 of midazolam and reduced EBT values , reflecting inhibition of both hepatic and intestinal CYP3A4 . In contrast , consumption of one glass of SS or DS GFJ increased midazolam AUC and Cmax , with little effect on the midazolam t1/2 and EBT values , reflecting preferential inhibition of intestinal CYP3A4 . Alterations of midazolam AUC and Cmax induced by nine glasses of DS GFJ were significantly greater than those produced by one glass of SS or DS GFJ . These data suggest that GFJ inhibits intestinal and hepatic CYP3A4 in an exposure-dependent fashion and that patients taking medications that are CYP3A4 substrates are at risk for developing drug-related adverse events if they consume large amounts of grapefruit juice To evaluate the effect of regular‐strength grapefruit juice , a cytochrome P4503A4 ( CYP3A4 ) inhibitor , on the pharmacokinetics of a commonly prescribed regimen of oral lovastatin Grapefruit juice produces a marked and variable increase in felodipine bioavailability . The pharmacokinetics of felodipine and its single primary oxidative metabolite , dehydrofelodipine , were studied after drug administration with 200 ml water , grapefruit juice , or naringin in water at the same concentration as the juice in a r and omized crossover trial of nine healthy men . With grapefruit juice , mean ± SEM felodipine area under the plasma concentration‐time curve ( AUC ) and peak plasma concentration ( Cmax ) were 206 % ± 23 % ( range , 123 % to 330 % , p < 0.01 ) and 170 % ± 24 % ( range , 127 % to 310 % , p < 0.02 ) , respectively , compared with water . Dehydrofelodipine/felodipine ratios for AUC ( 1.5 ± 0.2 versus 2.2 ± 0.2 , p < 0.001 ) and felodipine Cmax ( 1.5 ± 0.2 versus 2.2 ± 0.2 , p < 0.001 ) were reduced , consistent with inhibition of presystemic felodipine Output:	The current study indicated grapefruit juice‐drug interaction varies substantially based on patient characteristics and /or grapefruit juice product‐related factors , including the amount of furanocoumarin constituents present in the juice
MS21694	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background and purpose A programme based on eccentric exercises for treating subacromial pain was in a previous study found effective at 3-month follow-up . The purpose s of the present study were to investigate whether the results were maintained after 1 year and whether the baseline Constant-Murley score , rotator cuff status and radiological findings influenced the outcome . Patients and methods 97 patients on the waiting list for arthroscopic subacromial decompression had been r and omised to a specific exercise programme or unspecific exercises ( controls ) . After 3 months of exercises , the patients were asked whether they still wanted surgery and this option was available until a 1-year follow-up . 1 year after inclusion or 1 year after surgery , the number of patients who decided to have surgery in each group was compared . The choice of surgery was related to the baseline Constant-Murley score , ultrasound and radiographs taken at inclusion . Results All patients had improved significantly ( p<0.0001 ) in the Constant-Murley score at the 1-year follow-up . Significantly more patients in the control group decided to have surgery ( 63 % ) than those in the specific exercise group ( 24 % ; p<0.0001 ) . Patients who decided to have surgery had a significantly lower baseline Constant-Murley score and more often a full-thickness tear . Patients with partial tears did not differ from those with intact tendons . Interpretation The positive short-term results of specific exercises were maintained after 1 year , and this exercise strategy reduces the need for surgery . Full-thickness tear and a low baseline Constant-Murley score appear to be a predictive marker for a less good outcome . Trial registration number Clinical trials NCT01037673 STUDY DESIGN A prospect i ve r and omized clinical trial . OBJECTIVE To compare the effectiveness of 2 physical therapy treatment approaches for impingement syndrome of the shoulder . BACKGROUND Manual physical therapy combined with exercise is a commonly applied but currently unproven clinical treatment for impingement syndrome of the shoulder . METHODS AND MEASURES Thirty men and 22 women ( age 43 years + /- 9.1 ) diagnosed with shoulder impingement syndrome were r and omly assigned to 1 of 2 treatment groups . The exercise group performed supervised flexibility and strengthening exercises . The manual therapy group performed the same program and received manual physical therapy treatment . Both groups received the selected intervention 6 times over a 3-week period . The testers , who were blinded to group assignment , measured strength , pain , and function before treatment and after 6 physical therapy visits . Strength was a composite score of isometric strength tests for internal rotation , external rotation , and abduction . Pain was a composite score of visual analog scale measures during resisted break tests , active abduction , and functional activities . Function was measured with a functional assessment question naire . The visual analog scale used to measure pain with functional activities and the functional assessment question naire were also measured 2 months after the initiation of treatment . RESULTS Subjects in both groups experienced significant decreases in pain and increases in function , but there was significantly more improvement in the manual therapy group compared to the exercise group . For example , pain in the manual therapy group was reduced from a pretreatment mean ( + /- SD ) of 575.8 ( + /- 220.0 ) to a posttreatment mean of 174.4 ( + /- 183.1 ) . In contrast , pain in the exercise group was reduced from a pretreatment mean of 557.1 ( + /- 237.2 ) to a posttreatment mean of 360.6 ( + /- 272.3 ) . Strength in the manual therapy group improved significantly while strength in the exercise group did not . CONCLUSION Manual physical therapy applied by experienced physical therapists combined with supervised exercise in a brief clinical trial is better than exercise alone for increasing strength , decreasing pain , and improving function in patients with shoulder impingement syndrome Evidence -based practice involves the use of evidence from systematic review s and r and omised controlled trials , but the extent of this evidence in physiotherapy has not previously been surveyed . The aim of this survey is to describe the quantity and quality of r and omised controlled trials and the quantity of systematic review s relevant to physiotherapy . The Physiotherapy Evidence Data base ( PEDro ) was search ed . The quality of trials was assessed with the PEDro scale . The search identified a total of 2,376 r and omised controlled trials and 332 systematic review s. The first trial was published in 1955 and the first review was published in 1982 . Since that time , the number of trials and review s has grown exponentially . The mean PEDro quality score has increased from 2.8 in trials published between 1955 and 1959 to 5.0 for trials published between 1995 and 1999 . There is a substantial body of evidence about the effects of physiotherapy . However , there remains scope for improvements in the quality of the conduct and reporting of clinical trials OBJECTIVES : Conflicting results were reported about the effectiveness of Low level laser therapy on musculoskeletal disorders . The aim of this study was to investigate the effectiveness of 850‐nm gallium arsenide aluminum ( Ga‐As‐Al ) laser therapy on pain , range of motion and disability in subacromial impingement syndrome . METHODS : A total of 52 patients ( 33 females and 19 males with a mean age of 53.59±11.34 years ) with subacromial impingement syndrome were included . The patients were r and omly assigned into two groups . Group I ( n = 30 , laser group ) received laser therapy ( 5 joule/cm2 at each point over maximum 5‐6 painful points for 1 minute ) . Group II ( n = 22 , placebo laser group ) received placebo laser therapy . Initially cold pack ( 10 minutes ) was applied to all of the patients . Also patients were given an exercise program including range of motion , stretching and progressive resistive exercises . The therapy program was applied 5 times a week for 14 sessions . Pain severity was assessed by using visual analogue scale . Range of motion was measured by goniometer . Disability was evaluated by using Shoulder Pain and Disability Index . RESULTS : In group I , statistically significant improvements in pain severity , range of motion except internal and external rotation and SPADI scores were observed compared to baseline scores after the therapy ( p<0.05 ) . In Group II , all parameters except range of motion of external rotation were improved ( p<0.05 ) . However , no significant differences were recorded between the groups ( p>0.05 ) . CONCLUSIONS : The Low level laser therapy seems to have no superiority over placebo laser therapy in reducing pain severity , range of motion and functional disability Background : Repetitive or sustained elevated shoulder postures have been identified as a significant risk factor for occupationally related shoulder musculoskeletal disorders . Construction workers exposed to routine overhead work have high rates of shoulder pain that frequently progresses to functional loss and disability . Exercise interventions have potential for slowing this progression . Aims : To evaluate a therapeutic exercise programme intended to reduce pain and improve shoulder function . Methods : Construction worker volunteers were screened by history and clinical examination to test for inclusion /exclusion criteria consistent with shoulder pain and impingement syndrome . Sixty seven male symptomatic workers ( mean age 49 ) were r and omised into a treatment intervention group ( n = 34 ) and a control group ( n = 33 ) ; asymptomatic subjects ( n = 25 ) participated as an additional control group . Subjects in the intervention group were instructed in a st and ardised eight week home exercise programme of five shoulder stretching and strengthening exercises . Subjects in the control groups received no intervention . Subjects returned after 8–12 weeks for follow up testing . Results : The intervention group showed significantly greater improvements in the Shoulder Rating Question naire ( SRQ ) score and shoulder satisfaction score than the control groups . Average post-test SRQ scores for the exercise group remained below levels for asymptomatic workers . Intervention subjects also reported significantly greater reductions in pain and disability than controls . Conclusions : Results suggest a home exercise programme can be effective in reducing symptoms and improving function in construction workers with shoulder pain Objective To investigate the efficacy of a programme of manual therapy and exercise treatment compared with placebo treatment delivered by physiotherapists for people with chronic rotator cuff disease . Design R and omised , participant and single assessor blinded , placebo controlled trial . Setting Metropolitan region of Melbourne , Victoria , Australia . Participants 120 participants with chronic ( > 3 months ) rotator cuff disease recruited through medical practitioners and from the community . Interventions The active treatment comprised a manual therapy and home exercise programme ; the placebo treatment comprised inactive ultrasound therapy and application of an inert gel . Participants in both groups received 10 sessions of individual st and ardised treatment over 10 weeks . For the following 12 weeks , the active group continued the home exercise programme and the placebo group received no treatment . Main outcome measures The primary outcomes were pain and function measured by the shoulder pain and disability index , average pain on movement measured on an 11 point numerical rating scale , and participants ’ perceived global rating of overall change . Results 112 ( 93 % ) participants completed the 22 week trial . At 11 weeks no difference was found between groups for change in shoulder pain and disability index ( 3.6 , 95 % confidence interval −2.1 to 9.4 ) or change in pain ( 0.7 , −0.1 to 1.5 ) ; both groups showed significant improvements . More participants in the active group reported a successful outcome ( defined as “ much better ” ) , although the difference was not statistically significant : 42 % ( 24/57 ) of active participants and 30 % ( 18/61 ) of placebo participants ( relative risk 1.43 , 0.87 to 2.34 ) . The active group showed a significantly greater improvement in shoulder pain and disability index than did the placebo group at 22 weeks ( between group difference 7.1 , 0.3 to 13.9 ) , although no significant difference existed between groups for change in pain ( 0.9 , −0.03 to 1.7 ) or for the percentage of participants reporting a successful treatment outcome ( relative risk 1.39 , 0.94 to 2.03 ) . Several secondary outcomes favoured the active group , including shoulder pain and disability index function score , muscle strength , interference with activity , and quality of life . Conclusion A st and ardised programme of manual therapy and home exercise did not confer additional immediate benefits for pain and function compared with a realistic placebo treatment that controlled for therapists ’ contact in middle aged to older adults with chronic rotator cuff disease . However , greater improvements were apparent at follow-up , particularly in shoulder function and strength , suggesting that benefits with active treatment take longer to manifest . Trial registration Clinical trials NCT00415441 OBJECTIVE The aim of this study was to determine the effectiveness of Kinesio taping ( KT ) application added to the exercise treatment of subacromial impingement syndrome ( SIS ) . METHODS Thirty-eight ( 25 female , 13 male ) patients with SIS were r and omly divided into therapeutic KT ( n=19 ) and sham KT ( n=19 ) groups . All patients received the same exercise therapy in addition to therapeutic or sham KT at 3-day intervals for 12 days . The groups were compared according to pain , range of motion ( ROM ) , muscle strength and DASH and Constant scores before treatment and at the 5th and 12th treatment days . RESULTS Within group comparisons showed significant improvements in both groups at the 5th and 12th day evaluations ( p<0.05 ) . In comparisons between the groups , pain with movement and DASH scores in the therapeutic group were significantly lower at the 5th day ( p<0.01 ) . There were significant improvements in night pain , pain with movement , DASH score , shoulder external rotation muscle strength , and pain free shoulder abduction ROM in the therapeutic group at the 12th day ( p<0.05 ) . Passive shoulder flexion ROM increased more in the sham group at the 12th day ( p<0.05 ) . CONCLUSION The addition of KT application to the exercise program appears to be more effective than the exercise program alone for the treatment of SIS Background The physiotherapy dynamic humeral centring ( DHC ) aims to prevent subacromial impingement of rotator cuff tendons during elevation of the arm . The objective of the study was to determine whether DHC acts via an effect on subacromial impingement mechanism by assessing its effect on painful elevation of the arm in subacromial impingement syndrome . Methods This is a secondary analysis of results of a r and omised controlled trial of the effectiveness of DHC . Sixty-nine patients with subacromial impingement syndrome were prospect ively included . Patients and the assessor were blinded to the study hypothesis and treatment , respectively . Patients underwent DHC or non-specific mobilisation as a control for 6 weeks in 15 supervised individual outpatient sessions with home exercises . Outcomes were pain-free range of motion and presence of painful arc of the shoulder , both in active flexion and abduction of the arm at 3 months . Results At 3 months , pain-free range of motion , both flexion and abduction , was greater in the DHC group than in the mobilisation group . The number of patients with painful arc during flexion was decreased in the DHC group . Conclusions DHC improves painful active elevation of the arm . We suggest that DHC may act via a specific effect on subacromial impingement mechanism BACKGROUND AND PURPOSE Exercise therapy is a commonly used conservative therapy for long-term subacromial pain . However , there is no consensus regarding what type of exercises and dosage is most effective . The aim of this study was to compare the effect of two exercise programmes : 1 ) high-dosage ( HD ) medical exercise therapy versus 2 ) low-dosage ( LD ) exercise therapy Output:	Exercise therapy provided high evidence of being as effective as surgery intervention and better than no treatment or placebo treatment to improve pain , function and range of motion in the short , mid and long terms . The combination of mobilisation and exercises provided high evidence to decrease pain and improve function in the short term . There is limited evidence for improvements on the outcomes with the isolated application of manual therapy . High level of evidence was synthesis ed regarding the lack of beneficial effects of physical re sources such as low-level laser , ultrasound and pulsed electromagnetic field ( PEMF ) on pain , function or range of motion in the treatment of SAPS . There is limited evidence for microwave diathermy and transcutaneous electrical nerve stimulation . There is moderate evidence to no benefits with taping in the short term . Effects of diacutaneous fibrolysis and acupuncture are not well established yet . Exercise therapy should be the first-line treatment to improve pain , function and range of motion . The addition of mobilisations to exercises may accelerate reduction of pain in the short term .
MS21695	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The synthetic compound MC 903 ( calcipotriol ) is a structural analogue of the naturally occurring , biologically active 1,25-dihydroxyvitamin D3 [ 1,25-(OH)2-D3 ] . MC 903 and 1,25-(OH)2-D3 show similar receptor binding and comparable effects on cell differentiation . However , MC 903 appears to be at least 100 times less potent in its effects on calcium metabolism . In previous double-blind placebo-controlled studies , topical MC 903 has been shown to have a therapeutic effect in psoriasis . The present open study involving 20 patients with psoriasis vulgaris was a right/left comparison of the efficacy and tolerability of MC 903 ointment ( 50 micrograms/g ) alone or with UVB radiation . After treatment for 8 weeks , topical MC 903 alone result ed in marked improvement in 66 % of the patients and in clearance in 17 % . Combination of topical MC 903 with UVB result ed in marked improvement in 50 % of the patients and in clearance in 39 % . These differences were not statistically significant . No significant change in serum calcium levels was detected . Two patients developed a facial dermatitis which disappeared spontaneously during continued treatment . These results show that the combination of topical MC 903 and UVB radiation is well tolerated . Larger-scale studies are warranted to answer the question whether UVB radiation induces a significant improvement of the antipsoriatic effect of topical MC 903 Summary Combining PUVA with other therapeutic agents which reduce the UVA dose required for clearance of psoriasis may be of benefit by reducing the long‐term risk of cutaneous malignancy and by increasing the efficacy of treatment . We have therefore studied the effect of calcipotriol in 13 patients with plaque‐type psoriasis who were about to start twice weekly PUVA . In each patient , from the start of PUVA treatment , two plaques on symmetrical body sites were selected for assessment . Calcipotriol ointment was applied to one twice daily , and placebo to the other . Response was assessed weekly for 6 weeks : an investigator , unaware of treatment allocation . compared psoriasis severity within each of the plaques , and blood flux was measured using a scanning laser‐Doppler velocimeter . Of the 11 patients who completed the study , in nine the calcipotriol‐treated plaque either cleared before the placebo‐treated plaque ( n=7 ) or was consistently judged to be better ( n = 2 ) . From the third week of the trial , mean blood flux was significantly lower in the calcipotriol‐treated plaques than in those treated with placebo . In the seven patients whose psoriasis was clear in at least one plaque at the end of the study period , there was a median reduction in UVA dose of 26·5 % for calcipotriol compared with placebo . With the exception of one patient , the improved response was not associated with earlier relapse BACKGROUND A narrow-b and UVB lamp ( Philips TL 01 ) emitting a peak of approximately 311 nm was developed to improve the phototherapy for psoriasis . Only a few studies have been performed with promising results . OBJECTIVE The therapeutic efficacy of the Philips TL 01 lamp in a new 100 W version was compared with conventional broad-b and lamps ( Sylvania UV 6 ) in a controlled trial . METHODS Twenty-three patients with psoriasis were treated with half-body exposures from the different UVB sources . The rate of clearing was monitored by estimation of the Psoriasis Area and Severity Index . All patients used emollients ; excessive scaling was removed with salicylic acid in yellow petrolatum . In 13 patients dithranol in a modified Ingram regimen was added . In most cases the study was discontinued once a difference between the two sides was evident . RESULTS In 20 of 23 cases the TL 01 lamp proved to be significantly more effective than the conventional source . Application of dithranol provided a substantial additional therapeutic effect . With the high-intensity TL 01/100W bulbs , exposure times were comparable to broad-b and UVB phototherapy . CONCLUSION The therapeutic efficacy of Philips TL 01/100W and its practicability for psoriasis phototherapy have been demonstrated BACKGROUND Recent advances in the treatment of psoriasis include both the topical vitamin D analogue calcipotriol and cyclosporine . Combined treatments have been sought to decrease the incidence of side effects while maintaining efficacy in the treatment of severe chronic plaque psoriasis . OBJECTIVE The objective of this study was to evaluate the efficacy and safety of the combination of 2 mg/kg/day of cyclosporine with calcipotriol ointment ( 50 micrograms/gm ) in the treatment of severe plaque psoriasis . METHODS Sixty-nine patients were r and omly selected for this double-blind , multicenter study to receive cyclosporine ( 2 mg/kg/day ) combined with calcipotriol ointment ( 50 micrograms/gm ) or cyclosporine ( 2 mg/kg/day ) combined with placebo ointment ( vehicle of calcipotriol ) for a 6-week period . RESULTS Complete clearing or 90 % improvement in Psoriasis Area and Severity Index score occurred in 50.0 % of patients in the calcipotriol/cyclosporine group in comparison with 11.8 % of patients treated with placebo/cyclosporine ( p = 0.0019 ) . The confidence interval for the difference ranged from 17.8 % to 58.7 % . No difference was found between the two groups with respect to side effects . CONCLUSION The calcipotriol/cyclosporine combination was more effective than placebo/cyclosporine . Further studies are needed to establish the long-term efficacy and safety profile of this combination therapy OBJECTIVE The aim of this study was to evaluate the efficacy and tolerability of the association of calcipotriol ointment ( 50 micrograms/g ) plus cyclosporine versus cyclosporine alone in the treatment of moderate psoriasis ( mean PASI : 13 ) . METHODS Twenty patients were enrolled in this right-left open study . All the patients admitted were treated with cylosporine at an initial dose of 4.5 mg/kg/day ; in case of clinical improvement this dosage was reduced by 0.5 mg/kg/day every 15 days . In each patient we chose two similar , symmetrical lesions and calcipotriol ointment was applied only on the right lesion , twice a day , until the healing of the lesion or for 1 month . Patients were checked at baseline and every 15 days . RESULTS Eighteen patients completed the study and 17 of the 18 presented more evident improvement on the side treated with combined therapy , while only one patient showed a better result on the side treated with cyclosporine alone . A significant difference of the total score was already present after 15 days of therapy and was confirmed at the following check-ups . CONCLUSIONS These results underline the usefulness of the association of calcipotriol and cyclosporine in order to decrease the total dosage of cyclosporine Ro 10 - 9359 is a retinoic acid derivative , selected for study because of a better tolerance than retinoic acid , shown in animal experiments . Doses of 25 mg b.i.d . , 25 mg t.i.d . and 50 mg b.i.d . were administered orally to 27 patients suffering from severe chronic generalized psoriasis . The clinical efficacy was evaluated by means of a new index , psoriasis area and severity index ( PASI ) based on severity and area of psoriatic lesions . At doses of 25 mg t.i.d . or 50 mg b.i.d . Ro 10 - -9359 proved to be an extremely potent antipsoriatic drug . A more than 90 % reduction of psoriatic lesions could be seen in 10 patients out of 20 after 4 - 8 weeks of treatment . This good effect lasted about 5 weeks after treatment . Side effects were frequent , but mostly mild and completely reversible after termination of treatment Eighteen patients with symmetric plaque-type psoriasis were recruited for an open , controlled , bilateral half-body comparison study to evaluate the efficacy of calcipotriol/tar/UVB vs. anthralin/tar/UVB in a day care treatment setting . No patient had been on systemic antipsoriatic agents for at least 3 months prior to enrolment . One half-body was arbitrarily assigned to treatment with gradually increasing concentrations of anthralin as tolerated . The other half-body received calcipotriol ointment twice daily . Both sides received UVB and additional coal tar distillate in accordance with our st and ard day care regimen . Patients who were admitted to the day care program attended the clinic for UVB , anthralin , and calcipotriol on weekdays for two consecutive weeks . Anthralin was applied to psoriatic plaques on one side in the following fashion : anthralin 0.1 % with salicylic acid 3 % in zinc oxide paste on days 1 and 2 ; anthralin 0.2 % with salicylic acid 3 % in zinc oxide paste on days 3 - 5 ; anthralin 1 % with salicylic acid 3 % in hydrophilic petrolatum for 60 min on days 8 - 10 to thicker lesions ; and anthralin 2 % with salicylic acid 3 % in hydrophilic petrolatum for 60 min on day 11 to thicker lesions . On the contralateral side , calcipotriol ointment 0.05 microgram/mL ( Leo Pharmaceuticals , Ajax , Ontario ) was applied to lesions twice daily . No anthralin or calcipotriol was applied on weekends . All patients applied coal tar oil 50 % ( Doak Oil Forte , Trans CanaDerm , St-Laurent , Québec , equivalent to 5 % coal tar distillate ) with salicylic acid 5 % in hydrophilic petrolatum to their lesions at home in the evenings and on weekends . UVB ( FSX72T12 lamps , National Biologic Corporation , Twinsburg , Ohio ) was administered twice daily on weekdays in increasing doses as tolerated ( to erythema ) prior to the application of the topical medications . No trial medications were applied to the face , scalp , or genital regions . For clinical evaluation , the st and ard Psoriasis Activity and Severity Index ( PASI ) score was modified by splitting the score for area under 10 % ; the modified score ( mPASI ) for an area of coverage of 1%-4 % was 0.5 and for an area of 5%-9 % was 1 . The head and neck area was excluded from the analysis since neither anthralin nor calcipotriol was used at these sites . Each half-body was considered to represent 100 % in the area score determination . The maximum modified score for each side was 64.8 ( vs. 72 in the st and ard PASI scoring system ) . Clinical evaluations were completed at days 0 ( baseline ) , 3 , 7 , 10 , and 42 . The primary end-point was day 10 . On day 10 , patients were asked to compare the calcipotriol ointment to the anthralin on a five-point scale in terms of efficacy and irritancy and to state their future preferred treatment modality . Following discharge from day care , patients were continued on outpatient UVB and tar treatments three times weekly and asked to return for a repeat clinical assessment after 4 weeks ( day 42 ) . Blood sample s taken prior to treatment and at day 10 were analyzed for serum calcium . Comparisons of treatment efficacy were based on changes in the mPASI scores from onset of treatment to day 10 , as well as on the corresponding percentage changes . Analyses were carried out using the Wilcoxon test . Subjective patient comparisons of effectiveness and irritancy , as well as patient preference , were tested for equiprobability using the chi-square goodness-of-fit test with an examination of the adjusted residuals A total of 20 patients with symmetric plaque-type psoriasis were recruited for a controlled , investigator-blinded , right-left study . None of the patients had used any therapy other than emollients for 2 months prior to starting in the trial . All patients had a negative antinuclear antibody . By history , all patients had previously improved upon exposure to sunlight or ultraviolet light . Two symmetrical sites of equal severity were selected as target areas . Each patient was treated on one side with mineral oil twice daily and on the opposite side with calcipotriene 0.005 % ointment twice daily . The investigator was blinded as to which site received which topical treatment . Both sides were treated with equal doses of ultraviolet B ( UVB ) three times weekly in graduated suberythemogenic doses . Ultraviolet B radiation was emitted by a group of 6-ft fluorescent bulbs ( Light Sources FS72 T12 UVB HO ) in a st and ard phototherapy unit . The above regimen was continued for a total of 12 weeks . The severity of psoriasis in the target sites was rated by the examiner at baseline and at weekly intervals for the 12 weeks of study . Target sites were rated by severity of erythema , scaling , plaque elevation , and pruritus , with each of these parameters being assigned a score on a four-point scale : 0 , clear ; 1 , mild ; 2 , moderate ; 3 , severe . The four scores were added together to arrive at a total severity score for each of the target sites . Statistical analysis was performed using the paired t test , P values less than 0.05 were considered statistically significant . Eleven of the 20 patients ( 55 % ) Output:	RESULTS Antipsoriatic effects of acitretin , cyclosporine , and psoralen-UV-A phototherapy were enhanced with the addition of topical calcipotriene using the Psoriasis Area and Severity Index as the outcome , but this is not translated into an increase in the number of patients who achieve at least marked improvement . There is limited evidence that use of calcipotriene might reduce the cumulative exposure to phototherapy and systemic treatment . Overall , there is insufficient evidence to support any large effects in favor of combination treatment . In the patient assessment s , the results do not show an adjuvant effect , but there is some evidence that use of calcipotriene might reduce cumulative exposure to systemic therapy to obtain clearance . There were no long-term morbidity data on the effectiveness of any of the combinations studied .
MS21696	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : To evaluate atazanavir/ritonavir ( ATV/RTV ) ( 300/100 mg ) once daily , atazanavir/saquinavir ( ATV/SQV ) ( 400/1200 mg ) once daily , and lopinavir/ritonavir ( LPV/RTV ) ( 400/100 mg ) twice daily , each with tenofovir ( 300 mg ) once daily and a nucleoside reverse transcriptase inhibitor in treatment-experienced HIV-infected patients . Methods : R and omized , open-label , 48-week multicenter trial of 358 r and omized adult patients who had failed two or more prior HAART regimens with baseline HIV RNA ≥ 1000 copies/ml and CD4 cell count ≥ 50 × 106 cells/l . Results : The primary efficacy endpoint [ plasma HIV RNA reduction assessed by time-averaged difference ( TAD ) ] was similar for ATV/RTV and LPV/RTV [ TAD 0.13 ; 97.5 % confidence interval , −0.12 to 0.39 ] at 48 weeks . Mean reductions from baseline for ATV/RTV and LPV/RTV were comparable at 1.93 and 1.87 log10 copies/ml , respectively . Mean CD4 cell count increases were 110 and 121 × 106 cells/l for ATV/RTV , and LPV/RTV , respectively . The efficacy of ATV/SQV was lower than LPV/RTV by both these parameters . Declines in total cholesterol and fasting triglycerides were greater with ATV/RTV and ATV/SQV than with LPV/RTV ( P ≤ 0.005 ) . Lipids in the LPV/RTV arm at week 48 generally increased from baseline . Lipid-lowering agents were used more frequently in the LPV/RTV arm than in the ATV arms ( P < 0.05 versus ATV/RTV ) , as were antidiarrheal agents ( P ≤ 0.04 versus both ATV treatments ) . No new or unique safety findings emerged . Conclusions : ATV boosted with RTV is as effective and well tolerated as LPV/RTV in treatment-experienced patients , with a more favorable impact on serum lipids . Pharmacokinetically enhanced ATV provides a suitable choice for therapy of treatment-experienced HIV-infected patients BACKGROUND It is unclear whether metabolic or body composition effects differ between protease inhibitor-based regimens recommended for initial treatment of human immunodeficiency virus ( HIV ) infection . METHODS ATADAR is a phase 4 , open-label , multicenter , r and omized clinical trial . Stable antiretroviral-naive HIV-infected adults were r and omly assigned to atazanavir/ritonavir 300/100 mg or darunavir/ritonavir 800/100 mg in combination with tenofovir/emtricitabine daily . Predefined endpoints were treatment or virological failure , drug discontinuation due to adverse effects , and laboratory and body composition changes at 96 weeks . RESULTS At 96 weeks , 56 ( 62 % ) atazanavir/ritonavir and 62 ( 71 % ) darunavir/ritonavir patients remained free of treatment failure ( estimated difference 8.2 % ; 95 % confidence interval [ CI ] , -.6 to 21.6 ) and 71 ( 79 % ) atazanavir/ritonavir and 75 ( 85 % ) darunavir/ritonavir patients remained free of virological failure ( estimated difference 6.3 % ; 95 % CI , -.5 to 17.6 ) . Seven patients discontinued atazanavir/ritonavir and 5 discontinued darunavir/ritonavir due to adverse effects . Total and high-density lipoprotein cholesterol similarly increased in both arms , but there was a greater increase in triglycerides in the atazanavir/ritonavir arm . At 96 weeks , body fat ( estimated difference 2862.2 gr ; 95 % CI , 726.7 to 4997.7 ; P = .0090 ) , limb fat ( estimated difference 1403.3 gr ; 95 % CI , 388.4 to 2418.2 ; P = .0071 ) , and subcutaneous abdominal adipose tissue ( estimated difference 28.4 cm(2 ) ; 95 % CI , 1.9 to 55.0 ; P = .0362 ) increased more in the atazanavir/ritonavir arm than in darunavir/ritonavir arm . Body fat changes in the atazanavir/ritonavir arm were associated with higher insulin resistance . CONCLUSIONS We found no major differences between atazanavir/ritonavir and darunavir/ritonavir in efficacy , clinical ly relevant side effects , or plasma cholesterol fractions . However , atazanavir/ritonavir led to higher triglycerides and more total and subcutaneous fat than darunavir/ritonavir . Also , fat gains with atazanavir/ritonavir were associated with insulin resistance . Clinical Trials Registration . NCT01274780 BACKGROUND The use of either efavirenz or lopinavir-ritonavir plus two nucleoside reverse-transcriptase inhibitors ( NRTIs ) is recommended for initial therapy for patients with human immunodeficiency virus type 1 ( HIV-1 ) infection , but which of the two regimens has greater efficacy is not known . The alternative regimen of lopinavir-ritonavir plus efavirenz may prevent toxic effects associated with NRTIs . METHODS In an open-label study , we compared three regimens for initial therapy : efavirenz plus two NRTIs ( efavirenz group ) , lopinavir-ritonavir plus two NRTIs ( lopinavir-ritonavir group ) , and lopinavir-ritonavir plus efavirenz ( NRTI-sparing group ) . We r and omly assigned 757 patients with a median CD4 count of 191 cells per cubic millimeter and a median HIV-1 RNA level of 4.8 log10 copies per milliliter to the three groups . RESULTS At a median follow-up of 112 weeks , the time to virologic failure was longer in the efavirenz group than in the lopinavir-ritonavir group ( P=0.006 ) but was not significantly different in the NRTI-sparing group from the time in either of the other two groups . At week 96 , the proportion of patients with fewer than 50 copies of plasma HIV-1 RNA per milliliter was 89 % in the efavirenz group , 77 % in the lopinavir-ritonavir group , and 83 % in the NRTI-sparing group ( P=0.003 for the comparison between the efavirenz group and the lopinavir-ritonavir group ) . The groups did not differ significantly in the time to discontinuation because of toxic effects . At virologic failure , antiretroviral resistance mutations were more frequent in the NRTI-sparing group than in the other two groups . CONCLUSIONS Virologic failure was less likely in the efavirenz group than in the lopinavir-ritonavir group . The virologic efficacy of the NRTI-sparing regimen was similar to that of the efavirenz regimen but was more likely to be associated with drug resistance . ( Clinical Trials.gov number , NCT00050895 [ Clinical Trials.gov ] . ) BACKGROUND We assessed a once-daily combination to simplify therapy in patients infected with human immunodeficiency virus type 1 ( HIV-1 ) . METHODS A total of 355 adults with plasma HIV-1 RNA levels < 400 copies/mL were r and omly assigned to either switch to once-daily emtricitabine , didanosine , and efavirenz ( n=178 ) or maintain their protease inhibitor (PI)-based regimens ( n=177 ) . The primary end point was sustained suppression of plasma HIV-1 RNA levels to < 400 copies/mL. RESULTS At week 48 , the proportion of patients meeting the end point was 87.6 % in the PI group and 90.5 % in the once-daily group , with a treatment difference of -2.9 % ( upper bound of the 1-tailed 95 % confidence interval , 2.6 % ) . The proportion of patients with HIV-1 RNA levels < 50 copies/mL was higher in the once-daily group ( 87 % ) than in the PI group ( 79 % ) ( P<.05 ) . Resistance mutations to efavirenz and emtricitabine were detected in all patients in the once-daily group who experienced virologic failure while receiving study medication . The proportion of patients discontinuing study medication because of adverse events was similar between the once-daily group ( 9 % ) and the PI group ( 10 % ) ( P=.8 ) . CONCLUSIONS Substituting a convenient once-daily combination of emtricitabine , didanosine , and efavirenz for a PI-based regimen was well tolerated and associated with sustained virologic suppression Background : In BMS Study 045 , once-daily ( QD ) atazanavir/ritonavir ( ATV/RTV ) demonstrated comparable efficacy and safety to twice-daily ( BID ) lopinavir/ritonavir ( LPV/RTV ) over 48 weeks in treatment-experienced patients . Results of extended follow-up to 96 weeks are presented . Methods : BMS Study 045 was an open-label , r and omized , multi-national trial of HIV-infected patients with virologic failure on two or more prior HAART regimens design ed to evaluate the efficacy and safety of ATV/RTV ( 300/100 mg ) QD and LPV/RTV ( 400/100 mg ) BID , each with tenofovir ( 300 mg ) QD and one nucleoside reverse transcriptase inhibitor . The primary efficacy measure was the time-averaged difference ( TAD ) in reduction in HIV RNA from baseline . Secondary objectives included evaluation of safety and plasma lipid levels through week 96 . Results : Over 96 weeks , the ATV/RTV regimen demonstrated similar virologic efficacy to the LPV/RTV regimen . Mean reductions from baseline in HIV RNA were −2.29 and −2.08 log10 copies/ml , respectively [ TAD ( 97.5 % confidence interval ) : 0.14 log10 copies/ml ( −0.13 , 0.41 ) ] . The LPV/RTV regimen result ed in significant increases in total cholesterol ( + 9 % ) and fasting triglycerides ( + 30 % ) in comparison with the ATV/RTV regimen , which demonstrated decreases in these parameters [ −7 and −2 % , respectively , ( P < 0.0001 ) ] . Grade 2–4 diarrhoea occurred less frequently in ATV/RTV patients ( 3 % ) in comparison with LPV/RTV patients ( 13 % ) ( P < 0.01 ) . Grade 3–4 elevations in bilirubin were more common in ATV/RTV patients ( 53 % ) than LPV/RTV patients ( < 1 % ) ( P < 0.0001 ) , with no result ing discontinuations . Conclusions : Regimens containing once-daily ATV/RTV demonstrated comparable efficacy and safety , with significant reductions in total cholesterol and fasting triglycerides and improved gastrointestinal-tolerability in comparison with twice-daily regimens containing LPV/RTV over 96 weeks in treatment-experienced patients BACKGROUND Atazanavir/ritonavir is as effective as lopinavir/ritonavir , with a more favourable lipid profile and less gastrointestinal toxicity , in treatment-experienced HIV-1-infected patients . We compared these two combinations directly in treatment-naive patients . METHODS In this open-label , international non-inferiority study , 883 antiretroviral-naive , HIV-1-infected patients were r and omly assigned to receive atazanavir/ritonavir 300/100 mg once daily ( n=440 ) or lopinavir/ritonavir 400/100 mg twice daily ( n=443 ) , in combination with fixed-dose tenofovir/emtricitabine 300/200 mg once daily . R and omisation was done with a computer-generated central ised r and omisation schedule and was stratified by baseline levels of HIV RNA ( viral load ) and geographic region . The primary endpoint was the proportion of patients with viral load less than 50 copies per mL at week 48 . The main efficacy analysis was done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00272779 . FINDINGS At week 48 , 343 ( 78 % ) of 440 patients receiving atazanavir/ritonavir and 338 ( 76 % ) of 443 patients receiving lopinav Output:	The pooled effect estimate did not favor ATZ/r over DRV/r regarding the change in plasma levels of total cholesterol , triglycerides , or high-density lipoprotein at 24 , 48 , and 96 weeks . The ATZ/r regimen was generally as effective and well-tolerated as the LPV/r regimen for the treatment of HIV-1 patients . Compared to the DRV/r regimen , ATZ/r has no favorable effect on the plasma lipid profile or adipose tissue distribution
MS21697	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To assess the efficacy of endovascular aneurysm repair ( EVAR ) against st and ard alternative management in patients with large abdominal aortic aneurysm ( AAA ) . DESIGN Two national , multicentre r and omised trials - EVAR trials 1 and 2 . SETTING Patients were recruited from 38 out of 41 eligible UK hospitals . PARTICIPANTS Men and women aged at least 60 years , with an AAA measuring at least 5.5 cm on a computerised tomography scan that was regarded as anatomically suitable for EVAR , were assessed for fitness for open repair . Patients considered fit were r and omised to EVAR or open repair in EVAR trial 1 and patients considered unfit were r and omised to EVAR or no intervention in EVAR trial 2 . INTERVENTIONS EVAR , open repair or no intervention . MAIN OUTCOME MEASURES The primary outcome was mortality ( operative , all-cause and AAA related ) . Patients were flagged at the UK Office for National Statistics with central ly coded death certificates assessed by an Endpoints Committee . Power calculations based upon mortality indicated that 900 and 280 patients were required for EVAR trials 1 and 2 , respectively . Secondary outcomes were graft-related complications and re interventions , adverse events , renal function , health-related quality of life and costs . Cost-effectiveness analyses were performed for both trials . RESULTS Recruitment occurred between 1 September 1999 and 31 August 2004 , with targets exceeded in both trials : 1252 r and omised into EVAR trial 1 ( 626 to EVAR ) and 404 r and omised into EVAR trial 2 ( 197 to EVAR ) . Follow-up closed in December 2009 with very little loss to follow-up ( 1 % ) . In EVAR trial 1 , 30-day operative mortalities were 1.8 % and 4.3 % in the EVAR and open-repair groups , respectively : adjusted odds ratio 0.39 [ 95 % confidence interval ( CI ) 0.18 to 0.87 ] , p = 0.02 . During a total of 6904 person-years of follow-up , 524 deaths occurred ( 76 AAA related ) . Overall , there was no significant difference between the groups in terms of all-cause mortality : adjusted hazard ratio ( HR ) 1.03 ( 95 % CI 0.86 to 1.23 ) , p = 0.72 . The EVAR group did demonstrate an early advantage in terms of AAA-related mortality , which was sustained for the first few years , but lost by the end of the study , primarily due to fatal endograft ruptures : adjusted HR 0.92 ( 95 % CI 0.57 to 1.49 ) , p = 0.73 . The EVAR procedure was more expensive than open repair ( mean difference £ 1177 ) and not found to be cost-effective , but the model was sensitive to alternative assumptions . In EVAR trial 2 , during a total of 1413 person-years of follow-up , a total of 305 deaths occurred ( 78 AAA related ) . The 30-day operative mortality was 7.3 % in the EVAR group . However , this group later demonstrated a significant advantage in terms of AAA-related mortality , but this became apparent only after 4 years : overall adjusted HR 0.53 ( 95 % CI 0.32 to 0.89 ) , p = 0.02 . Sadly , this advantage did not result in any benefit in terms of all-cause mortality : adjusted HR 0.99 ( 95 % CI 0.78 to 1.27 ) , p = 0.97 . Overall , EVAR was more expensive than no intervention ( mean difference £ 10,222 ) and not found to be cost-effective . CONCLUSIONS EVAR offers a clear operative mortality benefit over open repair in patients fit for both procedures , but this early benefit is not translated into a long-term survival advantage . Among patients unfit for open repair , EVAR is associated with a significant long-term reduction in AAA-related mortality but this does not appear to influence all-cause mortality . TRIAL REGISTRATION Current Controlled Trials IS RCT N 55703451 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 16 , No. 9 . See the HTA programme website for further project information The modern era of aortic aneurysm repair started in AAA 4.0 - 5.5 cm in diameter . 5 The U.K Small AnEurope . The first successful resection of an abdominal eurysm Trial Participants were 126 vascular surgeons aortic aneurysm , with homograft replacement , was from 93 hospitals who collaborated in a r and omised performed in Paris on 25th March , 1951 , by Dubost trial to collect the evidence to answer the question : and colleagues , t Homografts were rapidly replaced does early elective surgery or ultrasound surveillance by prosthetic grafts of man-made fibres . Since then provide the better management for patmnts with small prostheses have been developed and st and ardised , AAA ? the operative techniques refined and anaesthesia has In the 4-year period between Autumn 1991 and improved . The number of aneurysms repaired electAutumn 1995 , 1090 patients , aged 60 - 76 years , were lvely each year continues to rise , with procedures m r and omised to a treatment policy of either early electEngl and and Wales having almost doubled recently , i ve surgery ( n=563 ) or a period of ultrasound surfrom 1405 to 2378 in the five years from 1990 - 1995 . 2 velllance ( n = 527 ) . Ultrasound surveillance was Few have stopped to consider to what extent the continued at regular intervals untd the anaurysm diapatmnt benefits from elective surgical repair of an meter exceeded 5.5 cm , the aneurysm became tender , abdominal aortic aneurysm . Since the start of ultraor the aneurysm grew by > 1 cm in a year . The trial sound screening programmes m the 1980s , more and protocol , together with details of how the trial was more asymptomatic abdominal aortic aneurysms executed , have been published previously in this ( AAAs ) are being detected . 3 Most of these screenjournal . 5 detected AAAs are small , < 5.5 cm in diameter . Should The end points of the UK Small Aneurysm Trial such aneurysms be repaired electlvely ? The first evlwere : all cause mortahty ; aneurysm related mortality ; dence to answer this question comes from Europe . quality of life ; costs and cost-effectiveness . The U K. Small Aneurysm Trial reported at the Annual An independent Data Monitoring and Ethics CornMeeting of the Vascular Surgical Society of Great Britmlttee review ed the progress of the trial after each ain and Irel and in November 1998 . 4 The evidence , successive 70 deaths and was empowered to stop the outlined below , indicates that elective open surgical trial at any point , should either one treatment arm repair of an asymptomatic AAA of < 5.5 cm in diameter be clearly superior or the 30-day operative mortahty should not be recommended , exceed 5 % ( allowing for appropriate confidence inThe U.K. Small Aneurysm Trial was established m tervals ) . The trial participants and Trial Steering Com1991 because many vascular surgeons in Britain were mittee were blind to all results until after the trial uncertain whether elective surgical aneurysm repair closed on 30th June , ] 998 . At this time the mean patient should be offered to patients with small asymptomatic follow-up was 4.6 years and 309 deaths had been recorded . At r and omisatlon , the baseline characteristics of the 563 patients r and omised to early elective surgery and Please address all correspondence to l T Powell , Imperial College School of Medicine , Charmg Cross Hospital , Fulham Palace Road , the 527 patients r and omised to ultrasound surveillance London W6 8RF , U K were very similar . The mean age of the surgery INTRODUCTION EVAR has the potential to improve outcome after ruptured abdominal aortic aneurysm ( AAA ) . Published series have been based upon selected population s. METHODS An interim analysis of a single centre prospect i ve r and omised controlled trial comparing endovascular aneurysm repair ( EVAR ) with open aneurysm repair ( OAR ) in patients with ruptured AAA was performed . Patients who had a ruptured AAA and who were considered fit for open repair were r and omised to EVAR or OAR after consent had been obtained . Those in the EVAR group had pre-operative spiral computed tomographic angiography ( CTA ) . The primary endpoint was operative ( 30-day ) mortality and secondary endpoints were moderate or severe operative complications , hospital stay and time between diagnosis and operation . A power study calculation required 100 patients to be recruited . RESULTS Between September 2002 and December 2004 , 103 patients were admitted with suspected ruptured AAA . Only 32 patients were recruited to the study . Of these , four patients died before receiving surgical treatment . On an intention to treat basis the 30-day mortality rate was 53 % in the EVAR group and 53 % in the OAR group . Moderate or severe operative complications occurred in 77 % in the EVAR group and in 80 % in the OAR group . Median total hospital stay in the EVAR group was 10 days ( inter-quartile range 6 - 28 ) and 12 days ( 4 - 52 ) in the OAR group . Median time between diagnosis and operation was 75 minutes ( 64 - 126 ) in the EVAR group and 100 minutes ( 48 - 138 ) in the OAR group . CONCLUSIONS Despite the relative high operative mortality in the EVAR group , these preliminary results show that it is possible to recruit patients to a r and omised trial of OAR and EVAR in patients with ruptured AAA . CT scanning does not delay treatment The objective of the Amsterdam Acute Aneurysm Trial is to study the combined outcome of conventional emergency surgery versus endovascular treatment for ruptured abdominal aortic aneurysms . The design used was a multicenter r and omized clinical trial conducted in two university hospitals and one teaching hospital in the Amsterdam region . The study included all patients with a ruptured abdominal aneurysm who were eligible for endovascular and conventional surgery . The primary end points were combined mortality and severe morbidity . The secondary end points were quality of life and cost-effectiveness . The background , design , and methods of this trial are presented , and the ethical and legal issues of this type of research are discussed INTRODUCTION acute haemodynamic changes and /or loss of abdominal muscle tone can occur during induction of general anaesthesia and may be the Achilles ' tendon in endovascular aneurysm repair ( EVAR ) of ruptured aortoiliac aneurysms ( rAIA ) . The purpose of this study was to evaluate the use of local anaesthesia ( LA ) for EVAR to overcome these limitations . METHODS twenty-one consecutive patients with rAIA are included in this study . Twenty patients underwent EVAR under LA , and 1 patient was treated under general anaesthesia . Haemodynamics were stabilised during assessment of EVAR feasibility by CT-scan and during the procedure itself by controlled hypotension ( MAP 50 - 60 mmHg ) and moderate fluid resuscitation . RESULTS median procedure time was 120 min . Haemodynamics remained stable in all but 3 patients who required transfemoral balloon occlusion of the supra-renal aorta . Perioperative intubation was necessary in 5 patients because of respiratory distress ( n=3 ) , or retroperitoneal access ( n=2 ) . Temporary deterioration of renal function occurred in 6 patients , with 2 requiring hemofiltration . CT-scan confirmed sealing of the rAIA in all patients at discharge . 30-day mortality was 9.5 % ( 2 deaths ) . In the median follow-up of 19 months , there were no deaths , but 3 endovascularre- interventions , 1 crossover femoro-femoral bypass , and 1 open surgical graft repair . DISCUSSION our series is the first to show that EVAR for rAIA can be safely performed under LA . This approach allows implantation of commercially available bifurcated SG and improves patient outcome BACKGROUND Although endovascular aneurysm repair ( EVAR ) has a lower 30-day operative mortality than open repair , the long-term results of EVAR are uncertain . We instigated EVAR trial 1 to compare these two treatments in terms of mortality , durability , health-related quality of life ( HRQL ) , and costs for patients with large abdominal aortic aneurysm ( AAA ) . METHODS We did a r and omised controlled trial of 1082 patients aged 60 years or older who had aneurysms of at least 5.5 cm in diameter and who had been referred to one of 34 hospitals proficient in the EVAR technique . We assigned patients who were anatomically suitable for EVAR and fit for an open repair to EVAR ( n=543 ) or open repair ( n=539 ) . Our primary endpoint was all-cause mortality , with secondary endpoints of aneurysm related mortality , HRQL , postoperative complications , Output:	For complication outcomes that did include at least 2 studies in the meta- analysis , there was no clear evidence to support a difference between eEVAR and open repair . Outcomes between eEVAR and open repair , specifically 30-day mortality , are similar .
MS21698	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A double-blind , r and omized trial was performed with 51 patients suffering from focal ischemic lesions in the territory of the middle cerebral artery . Intravenous infusions of 10 % glycerol in 0.9 % NaCI - 5 % glucose solutions were administered twice daily for 6 days to 26 patients , and the same amount of NaCI - glucose solutions to 25 controls . Glycerol did not reduce mortality ( 9 deaths in each group ) . The functional recovery was assessed by repeated neurological examinations during the 4 month trial . Glycerol significantly improved global performances and motor and sensory functions in patients with moderate disability , but its effect on global performances was transient . The patients with severe disability were not improved at all Abstract A double-blind evaluation of the effects of glycerol administration intravenously for 4 or 6 days in patients with acute stroke was completed in a stroke centre . Fifty-four patients with acute cerebral infa rct ion and eight patients with spontaneous intracerebral haemorrhage were admitted to the study . The neurological status was evaluated by use of a neurological scoring system . Patients with cerebral infa rct ion treated with glycerol showed significant improvement in neurological status compared to the patients treated with placebo ( The effects of intravenous glycerol and intravenous dextrose were compared using a double-blind trial in twenty-seven patients with acute stroke . Administration continued for up to 6 days . A st and ard scoring system was used for neurological evaluation . There was no difference in mortality or in improvement in neurological score between the two groups The results of clinical trials investigating various therapies in acute ischemic stroke have been inconsistent . The effect of glycerol therapy and a combination therapy of glycerol and dextran was evaluated in a double-blind , placebo-controlled study . Repeated neurologic examinations ( Day 0 , Weeks 1 , 6 , 12 , and 24 ) according to a modified Mathew score were performed on 62 patients . Statistical analysis showed no superiority of either treatment compared with placebo in acute ischemic stroke . A retrospective estimation of the Type II error of the study yielded approximately p = 0.25 . A major side effect was hemolysis in 98 % of patients treated with glycerol 1 . In patients with acute strokes entering a large ongoing r and omised double-blind controlled trial of intravenous glycerol therapy , the extent and pathogenesis of any ensuing haemolysis were evaluated using st and ard clinical investigations and in vitro techniques . 2 . Twenty patients received 10 % glycerol in saline ( 500 ml over 4 h on 6 consecutive days ) and 15 received corresponding control treatment with saline . 3 . Intravascular haemolysis was evident after the first infusion ; compared with the controls the glycerol group had i ) a greater mean reduction in serum haptoglobin concentration ( P less than .05 ) , and ii ) a greater proportion exhibiting haemoglobinaemia ( P = 0.03 ) . 4 . After 6 days of glycerol treatment , the mean reduction in haemoglobin concentration was only 0.8 g more than in controls ; this difference being neither clinical ly nor statistically significant . 5 . Glycerol therapy was not associated with haemoglobinuria , renal insufficiency or disseminated intravascular coagulation . 6 . Exposure of red blood cells to 1 - 10 % glycerol in vitro did not induce haemolysis per se ; on re-exposure to lower concentrations lysis ensued provided a minimum osmotic gradient was present . 7 . Whilst taking st and ard dosage regimes of glycerol , the stroke patients we studied manifested a degree of intravascular haemolysis but its consequences were not clinical ly significant ; lysis probably ensued after venous blood acquiring high glycerol concentrations mixed with blood containing little or no glycerol Background and Purpose This clinical trial investigates the effectiveness of intravenous glycerol therapy in patients with acute cortical infa rct ion in whom intracerebral hemorrhage was rigorously excluded . Methods Within 48 hours of symptoms from their first ischemic stroke , 113 hospital in patients were r and omized into the trial , provided that hemorrhage was excluded by computed tomography and informed consent was obtained . Patients were stratified into alert , semicoma , and coma groups using the Glasgow Coma Scale . Treatment was allocated according to a double-blind , r and omized protocol ; 56 patients received 500 mL of 10 % glycerol in saline over 4 hours on 6 consecutive days , and 57 patients received corresponding placebo treatment with saline . Using a variety of objective scoring systems , patient follow-up was up to 6 months . Results Corresponding measures of outcome in the glycerol and placebo groups were similar . At 6 months , respective mortality rates were 17 of 56 and 16 of 57 , and mean ±SD improvements in scores were 9.98±14.40 vs 10.51±12.68 ( long-term ) , 1.12±7.20 vs 1.57±6.30 ( prognostic ) , −1.94±5.53 vs −2.06±5.34 ( Glasgow Coma Scale ) , and 21.72±23.40 vs 11.94± 18.10 ( Barthel Index rating in survivors ) . Hemolysis ( generally sub clinical ) was the only adverse effect . Conclusions There was no clinical ly or statistically significant difference in outcome between the groups ; a trend toward greater functional recovery among survivors was evident after treatment with glycerol A prospect i ve study of 93 acute stroke patients r and omly selected by type of antiedema treatment given ( hypertonic glicerol infusion plus dexamethasone versus dexamethasone alone ) failed to elicit any statistically significant difference between the two treatments on survival rates and quality of survival 7 and 30 days after the stroke Intravenous administration of glycerol has been used in an effort to improve the prognosis for patients with acute cerebral infa rct ion . Fifty patients were treated actively and 56 served as a control group . The neurological status before , during and after treatment for six days was assessed by a score system . The patients were grouped according to the initial score . Those with the highest and lowest scores did not improve from glycerol infusion . However , the treated patients with intermediate scores , where the prognosis is known to be dubious , showed a significant improvement compared to the controls . The mortality was not influenced . No undesirable side-effects from glycerol were registered Background and Purpose Hitherto , treatment of acute cerebral hemorrhage with intravenous glycerol has not been evaluated in rigorous clinical studies with sufficient patient numbers . Methods We undertook a double-blind , stratified and r and omized , placebo-controlled clinical trial . Only patients with a first stroke admitted to the hospital within 24 hours after onset of symptoms were recruited , provided computed tomography confirmed hemorrhage and informed consent was obtained . After stratification into alert , semicoma , and coma subgroups using the Glasgow Coma Scale , 107 patients received active treatment ( 500 ml of 10 % glycerol in saline by intravenous infusion over 4 hours on 6 consecutive days ) and 109 were given corresponding saline treatment . Using a variety of objective scoring systems , patients were followed up for up to 6 months . Results At follow-up , all measures of outcome in the treated and control groups were very similar . At 6 months , respective mortality rates were 37 of 107 and 33 of 109 . Corresponding mean±SD improvements in Sc and inavian Stroke Study Group scores were 8.35±16.9 versus 11.55±15.6 ( long-term ) and 0.64±7.3 versus 2.40±6.9 ( prognostic ) , and improvements in the Barthel Index ratings were 10.72±24.7 versus 13.95±23.3 , respectively . Glasgow Coma Scale score improvements in the survivors were 0.81±1.5 and 1.16±1.7 in the treated and control groups , respectively . Hemolysis ( generally sub clinical ) was the only adverse effect of glycerol noted . Conclusions In the absence of any clinical ly or statistically significant difference in outcome between the treated and control groups , this trial provides no justification for glycerol therapy following acute cerebral The effects of intravenous glycerol in elderly patients with recent onset of acute ischaemic stroke were evaluated in a double-blind r and omised controlled trial . 173 patients received either 500 ml of a 10 % solution of glycerol in physiological saline or 500 ml of physiological saline administered intravenously over 4 h daily for 6 consecutive days . The number of deaths within the first week was 10 ( 12 % ) in the glycerol group versus 26 ( 30 % ) in the controls . Subsequent mortality up to 12 months was similar in the two groups and a survival analysis confirmed a beneficial effect of treatment ( p less than 0.02 ) . The neurological and functional recovery of survivors , their length of hospital stay , and the proportion able to return to live in their own home were similar in the two groups . The improvement in survival time with glycerol was achieved without serious adverse effects and without an increase in the proportion of survivors with severe residual disability 10 percent glycerol was given for 6 days to 30 patients who had had acute ischaemic cerebral infa rct ion , and the results were compared with those obtained after treating 31 similar patients with dexamethasone ( 16 mg . per 24 hours for 6 days ) . 1 patient treated with glycerol died of haemoglobinuria and acute renal failure . 6 patients treated with dexamethasone died--3 from cerebral oedema and 3 from non-neurological complications ( pulmonary embolism , myocardial infa rct ion , and aspiration pneumonia ) . Improvement was significantly greater in the glycerol group after 8 and 15 days . No improvement was noted using either glycerol or dexamethasone in 7 patients with spontaneous intracerebral haemorrhage Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews In a prospect i ve , community-based study of 675 consecutive patients with a first-ever stroke , of whom over 90 % had computed tomography ( CT ) and /or necropsy examinations , 129 deaths occurred within 30 days of the onset of symptoms , a case fatality rate ( CFR ) of 19 % . The 30 day CFR for patients with cerebral infa rct ion was 10 % ( 57 of 545 , for primary intracerebral haemorrhage 52 % ( 34 of 66 ) , for subarachnoid haemorrhage 45 % ( 15 of 33 ) and for those of uncertain pathological type 74 % ( 23 of 31 ) . The CFR for patients who had been functionally dependent pre-stroke was 33 % compared with 17 % for those who had been independent pre-stroke . The age-adjusted relative risk of death for patients who had been functionally dependent pre-stroke was not significantly greater ( 1.8 , 95 % confidence interval 0 to 4.3 ) . There was a significant trend for CFR to increase with age ( Chi square for trend = 4.0 , p less than 0.05 ) . This relationship was found in those patients who had been function Output:	The lack of evidence of benefit in long term survival does not support the routine or selective use of glycerol treatment in patients with acute stroke
MS21699	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIMS Despite widespread prevention efforts to decrease adolescent risk-taking , substance use and driving after drinking ( DD ) are prevalent in the United States . The current study compared the efficacy of an abbreviated version of Drug Abuse and Resistance Education ( DARE-A ) to a new Risk Skills Training Program ( RSTP ) . DESIGN Adolescent participation in drinking , drug use , DD and riding with a drunk driver was examined longitudinally . After baseline assessment s , adolescents were r and omly assigned to the RSTP . DARE-A or a no intervention control group and then completed 2-month post-test and 6-month follow-up assessment s. SETTING Adolescents attended a mid-sized suburban high school . PARTICIPANTS The sample ( N = 300 ) was comprised of 58 % females and the age range was 14 - 19 years . INTERVENTION The RSTP was developed to target several risk behaviors and to examine the feasibility of conducting a brief personalized prevention program in a group setting . DARE-A focused on increasing knowledge and underst and ing the deleterious effects of substance use . MEASUREMENTS Risk-taking behavior , perception of peer risk-taking and positive and negative alcohol expectancies were assessed . FINDINGS RSTP participants decreased participation in several risk behaviors at post-test , but reductions were not maintained at 6-month follow-up . The control and DARE-A groups increased their positive and decreased their negative alcohol expectancies . The control group increased their alcohol consumption . CONCLUSIONS Results suggest that a brief , personalized , group prevention program is a feasible approach to reducing adolescent risk-taking . Strategies must be developed to solidify these positive changes so that they are longer-lasting Abstract Objective : To evaluate the effectiveness of combinations of three methods to promote physical activity . Design : R and omised controlled trial . Baseline assessment with post-intervention follow up at 12 weeks and 1 year . Setting : One urban general practice , 1995 - 7 . Participants : 523 adults aged 40 to 64 years , r and omised to four intervention groups and a control group . Interventions : Brief ( one interview ) or intensive ( six interviews over 12 weeks ) motivational interviewing based on the stages of change model of behaviour change , with or without financial incentive ( 30 vouchers entitling free access to leisure facilities ) . Main outcome measures : Physical activity score ; sessions of moderate and vigorous activity in the preceding four weeks . Results : Response rate was 81 % at 12 weeks and 85 % at one year . More participants in the intervention group reported increased physical activity scores at 12 weeks than controls ( 38 % v 16 % , difference 22 % , 95 % confidence interval for difference 13 % to 32 % ) , with a 55 % increase observed in those offered six interviews plus vouchers . Vigorous activity increased in 29 % of intervention participants and 11 % of controls ( difference 18 % , 10 % to 26 % ) , but differences between the intervention groups were not significant . Short term increases in activity were not sustained , regardless of intensity of intervention . Conclusions : The most effective intervention for promoting adoption of exercise was the most intensive . Even this did not promote long term adherence to exercise . Brief interventions promoting physical activity that are used by many schemes in the United Kingdom are of question able effectiveness . Key messages Schemes promoting physical activity are currently popular in general practice in Britain , but few have been rigorously evaluated and their effectiveness is unknown . In this study , the most effective intervention for promoting adoption of physical activity was the most intensive , involving six motivational interviews and a financial incentive A comparatively brief intervention ( one interview ) was only effective in the short term in around a third of participants Short term increases in physical activity were not maintained at one year follow up and even the most intensive intervention was ineffective in promoting long term adherence to increased physical activity . National and local government , health authorities , and primary healthcare teams should be cautious about current and future expenditure on , and implementation of , exercise prescription or referral OBJECTIVES Message tailoring , based on individual needs and circumstances , is commonly used to enhance face-to-face patient counseling . Only recently has individual tailoring become feasible for printed messages . This study sought to determine whether printed tailored recommendations addressing women 's specific screening and risk status and perceptions about breast cancer and mammography are more effective than st and ardized printed recommendations . METHODS Computer-assisted telephone interviews were conducted with 435 women , aged 40 to 65 years , who had visited family practice groups within the previous 2 years . Subjects were r and omly allocated to receive individually tailored or st and ardized mammography recommendation letters mailed from physicians to patients ' homes . Follow-up interviews were conducted 8 months later . RESULTS Tailored letter recipients were more likely to remember and to have read more of their letters than st and ardized version recipients . After controlling for baseline status , tailored letter receipt was associated with more favorable follow-up mammography status for women with incomes below $ 26,000 and for Black women . CONCLUSIONS Tailored messages are a more effective medium for physicians ' mammography recommendations ; tailoring may be especially important for women of low socioeconomic status OBJECTIVES To examine the efficacy of UV photographs and information about photoaging ( eg , wrinkles and age spots ) for increasing the sun protection intentions and behaviors of young adults and to determine whether any effects of this appearance-based intervention could be enhanced by providing a non-UV alternative for achieving a tan ( ie , sunless tanning lotion ) . DESIGN R and omized control trial with 1-month follow-up . SETTING Two universities in Southern California . PARTICIPANTS A volunteer sample of 146 college students , 91.1 % of whom completed the " surprise " 1-month follow-up . INTERVENTION A UV facial photograph and a brief videotape describing the causes and consequences of photoaging . The study tested the effects of the photoaging information/UV photographic intervention only , the intervention plus use of sunless tanning lotion , and a control condition . MAIN OUTCOME MEASURES Participants sun protection intentions as assessed immediately after the intervention and sun protection behaviors during the month after the intervention as assessed during a surprise telephone follow-up . RESULTS The intervention result ed in significantly stronger sun protection intentions ( P<.001 ) and greater sun protection behaviors ( P<.05 ) relative to controls . Furthermore , the group that also used sunless tanning lotion tended to engage in greater sun protection behaviors than the group that received the intervention alone ( P<.08 ) . CONCLUSION The UV photographic intervention holds promise as a cost-effective approach to motivate practice s that may ultimately result in health benefits ( ie , reduced skin cancer rates ) Testing behavioral interventions to increase safer sex practice s of HIV+ individuals has the potential to significantly reduce the number of new infections . This study evaluated a behavioral intervention design ed to reduce the sexual risk behaviors of HIV+ individuals . HIV+ individuals ( N = 387 ) who reported engaging in unprotected sex with HIV- or partners of unknown serostatus were r and omly assigned to ( a ) a single counseling session targeting problem areas identified by the participant in 3 possible intervention domains ( i.e. , condom use , negotiation , disclosure ) ; ( b ) a single-session comprehensive intervention that covered all 3 intervention domains ; ( c ) the same comprehensive intervention , plus 2 monthly booster sessions ; or ( d ) a 3-session diet and exercise attention-control condition . The median number of unprotectedsex acts decreasedfrom 14 at baseline to6 , 6 , and 4 at 4- , 8- , and 12-month follow-ups , respectively . A repeated measures analysis of variance revealed a significant decrease in unprotected sex acts across all groups across time . A significant Group x Time interaction revealed that the comprehensive-with-boosters group had the most unprotected sex at 8-month follow-up as compared to the other 3 groups . These findings suggest that a brief intervention can result in large reductions in HIV transmission risks among HIV+ individuals , but the relative benefit of one intervention approach over another remains unclear The authors investigated the efficacy of an interactive Web site , MyStudentBody.com : Alcohol ( MSB : Alcohol ) that offers a brief , tailored intervention to help heavy drinking college students reduce their alcohol use . They conducted a r and omized , controlled clinical trial to compare the intervention with an alcohol education Web site at baseline , postintervention , and 3-month follow-up . Students were assessed on various drinking measures and their readiness to change their drinking habits . The intervention was especially effective for women and persistent binge drinkers . Compared with women who used the control Web site , women who used the intervention significantly reduced their peak and total consumption during special occasions and also reported significantly fewer negative consequences related to drinking . In addition , persistent heavy binge drinkers in the experimental group experienced a more rapid decrease in average consumption and peak consumption compared with those in the control group . The authors judged MSB : Alcohol a useful intervention for reaching important subgroups of college binge drinkers Motivational interviewing offers health care professionals a potentially effective strategy for increasing a patient 's readiness to change health behaviors . Recently , elements of motivational interviewing and the stages of change model have been simplified and adapted for use with patients in brief clinical encounters . This paper describes in detail a brief motivational intervention model to improve and renew dietary adherence with adolescents in the Dietary Intervention Study in Children ( DISC ) . DISC is a r and omized , multi-center clinical trial assessing the efficacy and safety of lowering dietary fat to decrease low-density lipoprotein cholesterol in high-risk children . In the first 3 years of follow-up covering ages 8 - 13 , intervention participants ( n = 334 ) were exposed to a family-based group intervention approach to change dietary choices . To address adherence and retention obstacles as participants moved into adolescence ( age 13 - 17 ) , an individual-level motivational intervention was implemented . The DISC motivational intervention integrates several intervention models : stages of change , motivational interviewing , brief negotiation and behavioral self-management . A preliminary test of the intervention model suggests that it was acceptable to the participants , popular with interventionists and appeared to be an age-appropriate shift from a family-based intervention model AIMS This clinical trial investigated effects of motivational enhancement treatment ( MET ) and group coping-skills training ( CST ) tailored for cocaine dependence . Effects of MET were hypothesized to be greater with CST and for less motivated patients . DESIGN AND INTERVENTIONS A 2 x 2 design investigated two individual sessions of MET compared to meditation-relaxation ( MRT ) , followed by four group sessions of CST versus drug education ( ED ) , as daily adjuncts to intensive treatment . SETTING The substance abuse program provided full-day treatment with a learning-theory and 12-Step orientation . PARTICIPANTS Cocaine-dependent patients were recruited . MEASUREMENTS Assessment included treatment retention ; change in cocaine-related urge , self-efficacy , pros and cons , and motivation ; substance use and problems during 12-month follow-up . Findings Of 165 patients , follow-up status is known for 90 % ( n = 149 ) . Patients in MET with low initial motivation to change reported less cocaine and alcohol relapse and use days and fewer alcohol problems than MET patients with higher initial motivation . MET produced more employment improvement than MRT , with no other significant benefit for MET . Patients with higher motivation had more cocaine use and alcohol problems after MET than MRT . Group CST reduced cocaine and alcohol use during follow-up for women only and reduced alcohol relapse for men and women . CONCLUSIONS MET is more beneficial for patients with lower initial motivation than for patients with high initial motivation . CST reduced cocaine and alcohol use for women only and reduced alcohol relapses , in contrast to results with lengthier individual CST OBJECTIVE The current study examined the efficacy of mailed personalized normative feedback ( PNF ) as a brief alcohol intervention for at-risk college drinkers , and investigated discrepancy as a possible mediator of the intervention effect . METHOD Participants consisted of 100 at-risk college drinkers who completed an alcohol-use assessment at baseline , 6-week posttest and 6-month follow-up . Measures included number of drinks consumed per heaviest drinking week , frequency of heavy-drinking episodes , peak blood alcohol concentration and number of alcohol-related problems , all for the last month . Participants were r and omly assigned to either a mailed brief intervention ( MBI ; n = 49 ) or attention-control ( C ; n = 51 ) group . The MBI group received mailed PNF that was based on baseline responses to the drinking measures ; the C group received a psychoeducational brochure about alcohol . RESULTS Mixed-model , repeated measures ANOVAs were used to examine the effects of time , group and gender on discrepancy and the drinking variables . Following the intervention , the MBI group reported significantly higher perceived discrepancy between self and others ' drinking than the C group . The MBI group reported consuming significantly fewer drinks per heaviest drinking week and engaging in heavy episodic drinking less frequently than the C group at the 6-week posttest ; however , these differences were no longer evident at the 6-month follow-up . Hierarchical regression analyses did not provide evidence for the hypothesized mediating effect of discrepancy . CONCLUSIONS Mailed PNF may be a cost- and time-efficient means of developing discrepancy and temporarily reducing heavy alcohol consumption among at-risk college drinkers OBJECTIVE Comorbidity of substance abuse disorders with schizophrenia is associated with a greater risk for serious illness complications and poorer outcome . Method ologically sound studies investigating treatment approaches for patients with these disorders are rare , although recommendations for integrated and comprehensive treatment programs abound . This Output:	A number of advantages of BI suggest they are well suited for translating behavioral research . In addition , findings from 13 systematic review s of BI effects show their potential versatility .

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