Split (3)

train · 14.2k rows

id stringlengths 4 8	query stringlengths 571 17.5k	answer stringlengths 12 3.68k
MS22500	*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 Low doses of some persistent organic pollutants ( POPs ) associate cross-sectionally with type 2 diabetes , whereas associations with high POP exposures are inconsistent . Objectives We investigated whether several POPs prospect ively predict type 2 diabetes within the Coronary Artery Risk Development in Young Adults ( CARDIA ) cohort . Methods Participants in this nested case – control study were diabetes free in 1987–1988 . By 2005–2006 , the 90 controls remained free of diabetes , whereas the 90 cases developed diabetes . Using serum collected in 1987–1988 , we measured 8 organochlorine pesticides , 22 polychlorinated biphenyl congeners ( PCBs ) , and 1 polybrominated biphenyl ( PBB ) . We compared POP concentrations from CARDIA and the National Health and Nutrition Examination Survey ( NHANES ) in 2003–2004 . We computed odds ratios ( ORs ) for incident diabetes using logistic regression analysis . Results Chlorinated POPs in CARDIA in 1987–1988 were much higher than corresponding NHANES 2003 - 2004 concentrations . POPs showed nonlinear associations with diabetes risk . The highest risk was observed in the second quartiles of trans-nonachlor , oxychlordane , mirex , highly chlorinated PCBs , and PBB153—a finding that suggests low-dose effects . We concentrated risk by summing these POPs and isolated very low concentrations of multiple POPs in the lowest sextile of the sum . The adjusted OR in the second sextile vs. the lowest sextile was 5.3 overall and 20.1 for body mass index ≥ 30 kg/m2 . Conclusions Several POPs at low doses similar to current exposure levels may increase diabetes risk , possibly through endocrine disruption . Certain POPs may a play a role in the current epidemic of diabetes , which has been attributed to obesity Background Studies have demonstrated ubiquitous human exposure to persistent organic pollutants ( POPs ) such as p , p′-diphenyldichloroethene ( DDE ) and polychlorinated biphenyls ( PCBs ) . Although there is considerable evidence that POP exposures are associated with prevalent diabetes , these studies do not establish causality because the cross-sectional study design does not allow for assessment of temporality of the exposure – disease association . Prospect i ve studies , however , have been lacking . Objectives This study was design ed to determine whether POP body burdens are related to incidence of diabetes in a cohort of Great Lakes sport fish consumers . Methods The cohort was established in the early 1990s and followed through 2005 . We tested serum for DDE and PCB congeners and assessed diabetes diagnosis , demographics , and fish consumption . Associations of diabetes with exposures were examined prospect ively in participants without diabetes in 1994–1995 , followed through 2005 . Annual percent changes in DDE and PCB-132/153 from 1994 to 2005 were examined by diabetes status . Results DDE exposure was associated with incident diabetes . Incident diabetes was not associated with mono-ortho PCB-118 , total PCBs , or years of sport fish consumption . Annual percent change in DDE and PCB-132/153 did not differ significantly by diabetes status . Conclusions This study demonstrates an association between DDE exposure and incident diabetes . The findings of an association of DDE with incident diabetes and the lack of effect of diabetes on annual percent change in POPs do not support the hypothesis that associations of POPs with diabetes are attributable to reverse causality . Additional studies should address the biological pathways by which DDE could affect glucose homeostasis PURPOSE Emerging evidence suggests that exposure to endocrine disruptors may initiate or exacerbate adiposity and associated health problems . This study examined sex differences in the association of urinary level of bisphenol-A ( BPA ) with selected indices of glucose homeostasis among U.S. adults . METHODS Data analyses were performed using a sample of 1586 participants from the 2005 to 2008 National Health and Nutrition Examination Surveys . BPA level and the ratio of BPA-to-creatinine level were defined as log-transformed variables and in quartiles . Selected indices of glucose homeostasis were defined using fasting glucose and insulin data . Multivariate linear and logistic regression models for the hypothesized relationships were constructed after controlling for age , sex , race , education , marital status , smoking status , physical activity , total dietary intake , and urinary creatinine concentration . RESULTS Taking the first quartile as a referent , the third quartile of BPA level was positively associated with log-transformed level of insulin and β-cell function ( homeostasis model assessment for β-cell function ) as well as insulin resistance ( log-transformed homeostasis model assessment for insulin resistance ; homeostasis model assessment for insulin resistance ≥2.5 ) , with significant BPA-by-sex interaction ; these associations were stronger among males than among females . Irrespective of sex , the ratio of BPA-to-creatinine level was not predictive of indices of glucose homeostasis . CONCLUSIONS A complex association may exist between BPA and hyperinsulinemia among adult U.S. men . Prospect i ve cohort studies are needed to further eluci date endocrine disruptors as determinants of adiposity-related disturbances Background : Polychlorinated biphenyls ( PCBs ) manufactured in Anniston , Alabama , from 1929 to 1971 caused significant environmental contamination . The Anniston population remains one of the most highly exposed in the world . Objectives : Reports of increased diabetes in PCB-exposed population s led us to examine possible associations in Anniston residents . Methods : Volunteers ( n = 774 ) from a cross-sectional study of r and omly selected households and adults who completed the Anniston Community Health Survey also underwent measurements of height , weight , fasting glucose , lipid , and PCB congener levels and verification of medications . Odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) were calculated to assess the relationships between PCBs and diabetes , adjusting for diabetes risk factors . Participants with prediabetes were excluded from the logistic regression analyses . Results : Participants were 47 % African American , 70 % female , with a mean age of 54.8 years . The prevalence of diabetes was 27 % in the study population , corresponding to an estimated prevalence of 16 % for Anniston overall ; the PCB body burden of 35 major congeners ranged from 0.11 to 170.42 ppb , wet weight . The adjusted OR comparing the prevalence of diabetes in the fifth versus first quintile of serum PCB was 2.78 ( 95 % CI : 1.00 , 7.73 ) , with similar associations estimated for second through fourth quintiles . In participants < 55 years of age , the adjusted OR for diabetes for the highest versus lowest quintile was 4.78 ( 95 % CI : 1.11 , 20.6 ) , whereas in those ≥ 55 years of age , we observed no significant associations with PCBs . Elevated diabetes prevalence was observed with a 1 SD increase in log PCB levels in women ( OR = 1.52 ; 95 % CI : 1.01 , 2.28 ) ; a decreased prevalence was observed in men ( OR = 0.68 ; 95 % CI : 0.33 , 1.41 ) . Conclusions : We observed significant associations between elevated PCB levels and diabetes mostly due to associations in women and in individuals < 55 years of age Low-dose organochlorine ( OC ) pesticides have recently been associated with type 2 diabetes in several non-Asian general population s. As there is currently epidemic type 2 diabetes in Asia , we investigated the associations between OC pesticides and type 2 diabetes in Koreans . Among subjects who participated in a community-based health survey , we r and omly selected 40 diabetic patients and 40 normal controls . Ten OC pesticides ( beta-hexachlorocyclohexane , hexachlorobenzene , heptachlor epoxide , p , p'-DDE , p , p'-DDD , p , p'-DDT , o , p'-DDT , oxychlordane , trans-nonachlor , and mirex ) detectable in > or=70 % of controls were analyzed in relation to diabetes . Most OC pesticides showed strong associations with type 2 diabetes after adjusting for age , sex , BMI , alcohol consumption , and cigarette smoking . Compared with subjects in the lowest tertile of each OC pesticide , adjusted odds ratios ( ORs ) in the 3rd tertile ranged from 3.1 ( 95 % CI 0.8 - 12.1 ) for heptachlor epoxide to 26.0 ( 95 % CI 1.3 - 517.4 ) for oxychlordane . In the case of chemicals belonging to the DDT family , adjusted ORs in the 3rd tertile were in the range of 10.6 ( 95 % CI 1.3 - 84.9 ) for p , p'-DDT to 12.7 ( 95 % CI 1.9 - 83.7 ) for p , p'-DDE . In this exploratory study with small sample , low-dose background exposure to OC pesticides was strongly associated with prevalent type 2 diabetes in Koreans even though absolute concentrations of OC pesticides were no higher than in other population s. Asians may be more susceptible to adverse effects of OC pesticides than other races Recent in vitro and animal studies have reported estrogen-like activity of chemicals used in sunscreen preparations . We investigated whether the three sunscreens benzophenone-3 ( BP-3 ) , octyl-methoxycinnamate ( OMC ) , and 3-(4-methylbenzylidene ) camphor ( 4-MBC ) were absorbed and influenced endogenous reproductive hormone levels in humans after topical application . In this 2-wk single-blinded study 32 healthy volunteers , 15 young males and 17 postmenopausal females , were assigned to daily whole-body topical application of 2 mg per cm(2 ) of basic cream formulation without ( week 1 ) and with ( week 2 ) the three sunscreens at 10 % ( wt/wt ) of each . Maximum plasma concentrations were 200 ng per mL BP-3 , 20 ng per mL 4-MBC , and 10 ng per mL OMC for females and 300 ng per mL BP-3 , 20 ng per mL 4-MBC , and 20 ng per mL OMC for men . All three sunscreens were detectable in urine . The reproductive hormones FSH , LH were unchanged but minor differences in testosterone levels were observed between the 2 wk . A minor difference in serum estradiol and inhibin B levels were observed in men only . These differences in hormone levels were not related to sunscreen exposure Aims /hypothesis Prospect i ve data directly investigating the role of endogenous sex hormones in diabetes risk have been scant , particularly in women . We aim ed to examine comprehensively plasma sex hormones in connection with risk of developing type 2 diabetes in postmenopausal women . Methods We conducted a prospect i ve , nested case – control study of plasma oestradiol , testosterone and dehydroepi and rosterone sulfate and risk of type 2 diabetes in a cohort of women health professionals with a mean age of 60.3 and 12.2 years since menopause . Among women not using hormone therapy and free of baseline cardiovascular disease , cancer and diabetes , 359 incident cases of type 2 diabetes were matched with 359 controls during an average follow-up of 10 years . Results Oestradiol and testosterone were each strongly and positively associated with risk of type 2 diabetes . After adjustment for BMI , family history , lifestyle and reproductive variables , the multivariable relative risks ( 95 % CI ) comparing the highest vs lowest quintile were 12.6 ( 2.83–56.3 ) for total oestradiol ( p = 0.002 for trend ) , 13.1 ( 4.18–40.8 ) for free oestradiol ( p < 0.001 for trend ) , 4.15 ( 1.21–14.2 ) for total testosterone ( p = 0.019 for trend ) and 14.8 ( 4.44–49.2 ) for free testosterone ( p < 0.001 for trend ) . These associations remained robust after adjusting and accounting for other metabolic syndrome components and baseline HbA1c levels . Conclusions /interpretationIn postmenopausal women , higher plasma levels of oestradiol and testosterone were strongly and prospect ively related to increased risk of developing type 2 diabetes . These prospect i ve data indicate that endogenous levels of sex hormones may play important roles in the pathogenesis of type 2 diabetes . Clinical Trials.gov ID no. : NCT00000479 BACKGROUND Bisphenol A ( BPA ) is Output:	Persistent and non-persistent EDCs may affect the risk of T2D .
MS22501	*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 Recurrent glioblastoma multiforme ( GBM ) is resistant to most therapeutic endeavors , with low response rates and survival rarely exceeding six months . There are no clearly established chemotherapeutic regimens and the aim of treatment is palliation with improvement in the quality of life . PATIENTS AND METHODS We report an open-label , uncontrolled , multicenter phase II trial of temozolomide in 138 patients ( intent-to-treat [ ITT ] population ) with glioblastoma multiforme at first relapse and a Karnofsky performance status ( KPS ) > or = 70 . One hundred twenty-eight patients were histologically confirmed with GBM or gliosarcoma ( GS ) by independent central review . Chemotherapy-naïve patients were treated with temozolomide 200 mg/m2/day orally for the first five days of a 28-day cycle . Patients previously treated with nitrosourea-containing adjuvant chemotherapy received 150 mg/m2/day for the first five days of a 28-day cycle . In the absence of grade 3 or 4 toxicity , patients on the 150 mg/m2 dose schedule were eligible for a 200 mg/m2 dose on the next cycle . RESULTS The primary endpoint was six-month progression-free survival assessed with strict radiological and clinical criteria . Secondary endpoints included radiological response and Health-related Quality of Life ( HQL ) . Progression-free survival at six months was 18 % ( 95 % confidence interval ( CI ) : 11%-26 % ) for the eligible-histology population . Median progression-free survival and median overall survival were 2.1 months and 5.4 months , respectively . The six-month survival rate was 46 % . The objective response rate ( complete response and partial response ) determined by independent central review of gadolinium-enhanced magnetic resonance imaging ( MRI ) scans was 8 % for both the ITT and eligible-histology population s , with an additional 43 % and 45 % of patients , respectively , having stable disease ( SD ) . Objective ly assessed response and maintenance of a progression-free status were both associated with HQL benefits ( characterized by improvements over baseline in HQL domains ) . Temozolomide had an acceptable safety profile , with only 9 % of therapy cycles requiring a dose reduction due to thrombocytopenia . There was no evidence of cumulative hematologic toxicity . CONCLUSIONS Temozolomide demonstrated modest clinical efficacy , with an acceptable safety profile and measurable improvement in quality of life in patients with recurrent GBM . The use of this drug should be explored further in an adjuvant setting and in combination with other agents 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 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 One of the objectives of this phase II study was to determine whether temozolomide ( TMZ ) improved the health-related quality of life ( HRQL ) of patients with recurrent anaplastic astrocytoma ( AA ) . HRQL was assessed at baseline ( pretreatment ) and every 4 weeks at each treatment cycle using the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 ) ( version 2.0 ) and the Brain Cancer Module ( BCM20 ) . Changes from baseline in the scores of seven preselected HRQL domains ( role and social functioning , global QL , visual disorder , motor dysfunction , communication deficit and drowsiness ) were determined at 6 months as well as prior to , and at the time of , disease progression . The significance of the changes was assessed by calculating statistical significance , effect sizes and the proportions of patients with improvement in their HRQL scores ( changes of > /=10 points ) . After 6 months of treatment , patients who were free of progression of disease reported either an improvement or maintenance of all the preselected HRQL domains scores . Patients with disease progression by 6 months usually experienced improvement in HRQL before progression , but there was a sharp decline in most of the preselected domains at progression . We conclude that treatment of recurrent AA with temozolomide is associated with significant HRQL benefits PURPOSE To determine whether chemotherapy with temozolomide ( TMZ ) versus procarbazine ( PCB ) for recurrent glioblastoma multiforme ( GBM ) was associated with improvement in health-related quality of life ( HRQOL ) . PATIENTS AND METHODS HRQOL was assessed at baseline and during treatment using the European Organization for Research and Treatment of Cancer Quality of Life Question naire C30 and a Brain Cancer Module ( BCM20 ) in two clinical trials that enrolled a total of 366 patients . Two hundred eighty-eight patients provided HRQOL data that could be used for analysis ; 109 patients received TMZ in a phase II study , whereas 89 patients received TMZ and 90 received PCB in a r and omized phase III study . Changes from baseline in the scores of seven preselected HRQOL domains ( role and social functioning , global quality of life [ QOL ] , visual disorders , motor dysfunction , communication deficit , and drowsiness ) were calculated for all groups . Statistical significance , effect sizes , and proportions of patients with improved HRQOL scores ( changes of > or = 10 points ) were calculated . RESULTS Before disease progression , patients treated with TMZ were found to have an improvement in most of the preselected HRQOL domain scores compared with their baseline ( pretreatment ) scores . Those who were progression-free on TMZ at 6 months had improvement in all the preselected HRQOL domains . Conversely , patients treated with PCB reported deterioration in HRQOL that was independent of whether or not the disease had progressed by 6 months . Patients with disease progression , regardless of treatment , experienced a sharp decline in all domains at the time of progression . CONCLUSION Treatment with TMZ was associated with improvement in HRQOL scores compared with treatment with PCB . The deterioration reported by PCB-treated patients was likely because of toxicity . Delaying disease progression by treatment with TMZ is beneficial to the HRQOL status of patients with recurrent GBM Temozolomide , a new oral cytotoxic agent , was given to 75 patients with malignant gliomas . The schedule used was for the first course 150 mg/m2 per day for 5 days ( i.e. total dose 750 mg/m2 ) , escalating , if no significant myelosuppression was noted on day 22 , to 200 mg/m2 per day for 5 days ( i.e. total dose 1000 mg/m2 ) for subsequent courses at 4-week intervals . There were 27 patients with primary disease treated with two courses of temozolomide prior to their radiotherapy and 8 ( 30 % ) fulfilled the criteria for an objective response . There were 48 patients whose disease recurred after their initial surgery and radiotherapy and 12 ( 25 % ) fulfilled the criteria for an objective response . This gave an overall objective response rate of 20 ( 27 % ) out of 75 patients . Temozolomide was generally well tolerated , with little subjective toxicity and predictable myelosuppression . However , the responses induced with this schedule were of short duration and had relatively little impact on overall survival . In conclusion , temozolomide given in this schedule has activity against high grade glioma . However , studies evaluating chemotherapy in primary brain tumours should include a quality -of-life/performance status evaluation in addition to CT or MRI scanning assessment Output:	The key results were that temozolomide may increase progression-free survival but has no significant impact on overall length of survival . Temozolomide appears to produce few serious adverse effects and may also have a positive impact on health-related quality of life . Overall the evidence -base is weak and few strong conclusions can be drawn regarding the effectiveness of temozolomide .
MS22502	*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 We compared postoperative outcomes in patients treated with laparoendoscopic single site varicocele ligation with or without testicular artery and lymphatic preservation . MATERIAL S AND METHODS A total of 80 patients with left varicocele were r and omly divided into 2 groups and treated with laparoendoscopic single site varicocele ligation with preservation of the testicular artery and lymphatics ( 40 in group 1 ) or complete ligation of the testicular vessels and lymphatics ( 40 in group 2 ) . Operative time , hospital stay , return to normal activity , postoperative visual analog scale pain scores and complications were analyzed . In patients with subfertility preoperative and 3-month postoperative semen analyses were performed . In patients with scrotal pain preoperative and 12-month postoperative visual analog scale pain scores were analyzed . RESULTS A total of 35 patients per group completed the study . Hospital stay , return to normal activity and postoperative pain scores did not differ between the groups . No major complications were observed . Mean ± SD operative time was 60.7 ± 10.7 and 48.6 ± 6.0 minutes in groups 1 and 2 , respectively ( p < 0.001 ) . Patients with subfertility , including 22 in group 1 and 21 in group 2 , showed improved semen parameters 3 months postoperatively but postoperative values did not differ between the groups . The 17 patients in each group with scrotal pain showed decreased pain scores 12 months postoperatively with no difference between the groups . CONCLUSIONS Laparoendoscopic single site varicocele ligation is feasible . No differences in postoperative outcomes and complications were observed when preserving or not preserving the testicular artery and lymphatics To evaluate , in a r and omized prospect i ve trial in children and adolescents , the feasibility of isosulphan blue‐based lymphatic vessel preservation during laparoscopic varicocelectomy and its impact on the complication rate , as the operative management of varicoceles remains controversial A surgical method of varicocelectomy , in which the internal spermatic veins together with the testicular artery are ligated as a whole in the retroperitoneal space , has been proposed as a simple and reliable procedure . We evaluated the effects of ligating the testicular artery at varicocelectomy on fertility . A total of 34 subfertile patients with a left varicocele was r and omized into an artery-preserved or artery-ligated group at open varicocelectomy and the change in semen quality was prospect ively studied . The artery-preserved group showed improvements in sperm density and total sperm count , while the artery-ligated group showed improvements in sperm density , total sperm count and sperm motility . The results indicated identical improvement in semen quality in both groups of patients . Testicular volume , measured by a punched-out orchidometer , did not change in any of the patients in the ligated group , except for 1 with a grade 3 varicocele , although this decrease could not be detected by sonography . The effects of artery-preserving and artery-ligating varicocelectomy on postoperative pregnancy rates were investigated by examining 116 patients retrospectively . The pregnancy rates of 37.8 % and 23.8 % in the artery-preserved and artery-ligated groups , respectively , were not significantly different . Despite the theoretical advantage of artery preservation , our study did not show any significant difference between artery-preserving varicocelectomy and the artery-ligating operation when improvements in semen quality and postoperative pregnancy rate were evaluated Objective : To prospect ively compare the recurrence rate and short postoperative outcome after r and omized laparoscopic varix ligation with internal spermatic artery ( ISA ) preservation versus laparoscopic varix ligation with ISA ligation . Material and methods : Twenty-five patients with 35 varicocele who required varix ligation for infertility in 13 patients , scrotal pain in 15 patients and scrotal swelling in 2 patients who underwent one of two procedures : laparoscopic varix ligation with ISA prservation ( Group A ) or laparoscopic varix ligation with ISA ligation ( Group B ) were postoperatively evaluated for short post operative outcome and underwent percutaneous spermatic venograms to detect recurrence . Fisher 's Exact Test was used for statistical analysis . Results : Recurrence through parallel collaterals was noted in 39 % and 5.9 % in Group A and Group B respectively as demonstrated on percutaneous spermatic venous venography ( PSV ) ( statistically significant p = 0.0408 ) . Preoperative pain completely resolved in all patients in Group B and persisted in 45 % in Group A. However , this was not statistically significant ( p = 0.088 ) . No testicular atrophy or hydrocele formation was noted in either group . Conclusions : Laparoscopic varix ligation with ISA ligation has lower recurrence rate than laparoscopic varix ligation without ISA ligation and may provide better varicocele related pain control with no increase in hydrocele or testicular atrophy rate . We recommend ISA ligation routinely during laparoscopic varix ligation Objectives : Testicular blood supply and semen quality were compared in two groups of patients undergoing laparoscopic varicocelectomy : group I ( n = 27 ) with spermatic artery ligation and group II ( n = 48 ) with spermatic artery preservation . Methods : Laparoscopic varicocelectomy was performed on 75 patients divided on the basis of whether ligation took place during surgery or not . The blood flow parameter ( resistance index – RI ) measured using color Doppler sonography was the index of vascular efficiency selected . Results : Mean RI was 0.69 in group I and 0.65 in group II . The difference was not significant . Both groups showed improvements in sperm density and motility but there was no significant difference between groups for either parameter . Conclusion : Using color Doppler sonography confirms that ligation of the testicular artery during varicocelectomy does not lead to major changes in testicular blood supply or sperm quality The aim of this prospect i ve study was to assess long-term functional results ( spermiograms ) in subjects who underwent laparoscopic varicocelectomy via either of 2 procedures ( ligation or preservation of testicular artery ) . A total of 122 patients underwent laparoscopic varicocelectomy performed via either of the 2 different procedures : complete ligation of the spermatic vessels or preservation of the spermatic artery . After surgery when patients achieved 18 years , they were asked to undergo semen analysis . Spermiogram results were divided into 2 subgroups : " normal " and " abnormal . " We analyzed volume , sperm count per mL , percentage of motile spermatozoa , percentage of normal spermatozoa , and percentage of vitality for each group . Both groups showed the same results in terms of " normal " and " abnormal " spermiograms ( World Health Organization criteria ) , but analysis showed higher sperm concentration per mL , sperm motility , volume , vitality , and rate of morphologically normal sperm for the group with arteries preserved and " normal " spermiograms ( P < .01 ) . Analysis of data from the spermiograms showed that preservation of the testicular artery was the best possible option in terms of semen quality . Therefore , we believe that surgical treatment of varicocele should be carried out using procedures involving artery preservation PURPOSE There is evidence that varicocele damage , as reflected by loss of testicular mass , is most striking in the pubertal age group . We attempted to evaluate the long-term effect of early varicocele treatment on testicular growth and sperm count and , thus , determine its prophylactic value . MATERIAL S AND METHODS We compared testicular mass and sperm count in 32 men ( mean age 28 years ) who underwent surgery for varicocele at 11 to 15 years old ( mean age 13 ) to those in 26 untreated , age matched men ( mean age 30 years ) with varicocele and 27 male controls ( mean age 25 years ) . Mean followup in the treated group was 14.5 years ( range 12 to 20 ) . Testicular volumes were measured by ultrasonography . RESULTS There was no significant difference between left and right testicular volumes in the treated or control group , in contrast to the untreated group , in which the left testicles were significantly smaller . Comparison of testicular mass showed a striking similarity between the treated and control groups , while there was a significant difference when the untreated group was compared to the control and operated groups . Total sperm counts were significantly less in the untreated than the treated and control groups . CONCLUSIONS These data support the notion that testicular hypotrophy related to varicocele may be reversed by early intervention and they further strengthen the indication for varicocelectomy in children Output:	Conclusion With the advantages of less recurrence , easier operating and less time spending , and comparable results in other respects , artery non-preserving is preferable to artery preserving in laparoscopic varicocelectomy , although there is a relatively high incidence of hydrocele formation .
MS22503	*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 To test the effect of education and support by a nurse on self-care and re source utilization in patients with heart failure . METHODS A total of 179 patients ( mean age 73 , 58 % male , NYHA III-IV ) hospitalized with heart failure were evaluated prospect ively . Patients were r and omized to the study intervention or to ' care as usual ' . The supportive educative intervention consisted of intensive , systematic and planned education by a study nurse about the consequences of heart failure in daily life , using a st and ard nursing care plan developed by the research ers for older patients with heart failure . Education and support took place during the hospital stay and at a home visit within a week of discharge . Data were collected on self-care abilities , self-care behaviour , readmissions , visits to the emergency heart centre and use of other health care re sources . RESULTS Education and support from a nurse in a hospital setting and at home significantly increases self-care behaviour in patients with heart failure . Patients from both the intervention and the control group increased their self-care behaviour within 1 month of discharge , but the increase in the intervention group was significantly more after 1 month . Although self-care behaviour in both groups decreased during the following 8 months , the increase from baseline remained statistically significant in the intervention group , but not in the control group . No significant effects on re source utilization were found . CONCLUSIONS Intensive , systematic , tailored and planned education and support by a nurse results in an increase in patients ' self-care behaviour . No significant effects were found on use of health care re sources . Additional organisational changes , such as longer follow-up and the availability of a heart failure specialist would probably enhance the effects of education and support Hospital admissions due to chronic obstructive pulmonary disease ( COPD ) exacerbations have a major impact on the disease evolution and costs . The current authors postulated that a simple and well-st and ardised , low-intensity integrated care intervention can be effective to prevent such hospitalisations . Therefore , 155 exacerbated COPD patients ( 17 % females ) were recruited after hospital discharge from centres in Barcelona ( Spain ) and Leuven ( Belgium ) . They were r and omly assigned to either integrated care ( IC ; n = 65 ; age mean±sd 70±9 yrs ; forced expiratory volume in one second ( FEV1 ) 1.1±0.5 L , 43 % predicted ) or usual care ( UC ; n = 90 ; age 72±9 yrs ; FEV1 1.1±0.05 L , 41 % pred ) . The IC intervention consisted of an individually tailored care plan upon discharge shared with the primary care team , as well as accessibility to a specialised nurse case manager through a web-based call centre . After 12 months ’ follow-up , IC showed a lower hospitalisation rate ( 1.5±2.6 versus 2.1±3.1 ) and a higher percentage of patients without re-admissions ( 49 versus 31 % ) than UC without differences in mortality ( 19 versus 16 % , respectively ) . In conclusion , this trial demonstrates that a st and ardised integrated care intervention , based on shared care arrangements among different levels of the system with support of information technologies , effectively prevents hospitalisations for exacerbations in chronic obstructive pulmonary disease patients OBJECTIVE To determine the effect of a home-based intervention ( HBI ) on the frequency of unplanned readmission and out-of-hospital death among patients discharged home from acute hospital care . DESIGN A r and omized controlled trial comparing HBI with usual care ( UC ) . SETTING A tertiary referral hospital servicing the northwestern region of Adelaide , South Australia . PARTICIPANTS Medical and surgical patients ( n = 762 ) discharged home after hospitalization . INTERVENTION Home-based intervention ( n = 381 ) consisted of counseling of all patients before discharge followed by a single home visit ( by a nurse and pharmacist ) to those patients considered to be at high risk of readmission ( n = 314 ) in order to optimize compliance with and knowledge of the treatment regimen , identify early clinical deterioration , and intensify follow-up of such patients where appropriate . MEASUREMENTS The primary endpoint was the number of unplanned readmissions plus out-of-hospital deaths over a 6-month follow-up period . RESULTS During the study follow-up , the major endpoint occurred most commonly in the UC group ( 217 vs 155 episodes : P < .001 ) . Overall , the HBI group demonstrated fewer unplanned readmissions ( 154 vs 197 : P = .022 ) , out-of-hospital deaths ( 1 vs. 20 : P < .001 ) , total deaths ( 12 vs. 29 : P = .006 ) , emergency department attendances ( 236 vs 314 : P < .001 ) , and total days of hospitalization ( 1452 vs 1766 : P < .001 ) . There was a disproportionate reduction in multiple events among HBI patients ( P = .035 ) . Hospital-based costs of health care during study follow-up tended to be lower in the HBI group ( $ A2190 vs $ A2680 per patient : P = .102 ) . Mean cost of HBI was $ A190 per patient visited , whereas other community-based health care costs were similar for both groups . CONCLUSIONS Among high-risk patients discharged from acute hospital care , HBI is beneficial in limiting unplanned readmissions and reducing risk of out-of-hospital death . It may be particularly cost-effective if applied selectively to patients with a history of frequent unplanned hospital admission BACKGROUND Patients with complex care needs who require care across different health care setting s are vulnerable to experiencing serious quality problems . A care transitions intervention design ed to encourage patients and their caregivers to assert a more active role during care transitions may reduce rehospitalization rates . METHODS R and omized controlled trial . Between September 1 , 2002 , and August 31 , 2003 , patients were identified at the time of hospitalization and were r and omized to receive the intervention or usual care . The setting was a large integrated delivery system located in Colorado . Subjects ( N = 750 ) included community-dwelling adults 65 years or older admitted to the study hospital with 1 of 11 selected conditions . Intervention patients received ( 1 ) tools to promote cross-site communication , ( 2 ) encouragement to take a more active role in their care and to assert their preferences , and ( 3 ) continuity across setting s and guidance from a " transition coach . " Rates of rehospitalization were measured at 30 , 90 , and 180 days . RESULTS Intervention patients had lower rehospitalization rates at 30 days ( 8.3 vs 11.9 , P = .048 ) and at 90 days ( 16.7 vs 22.5 , P = .04 ) than control subjects . Intervention patients had lower rehospitalization rates for the same condition that precipitated the index hospitalization at 90 days ( 5.3 vs 9.8 , P = .04 ) and at 180 days ( 8.6 vs 13.9 , P = .046 ) than controls . The mean hospital costs were lower for intervention patients ( $ 2058 ) vs controls ( $ 2546 ) at 180 days ( log-transformed P = .049 ) . CONCLUSION Coaching chronically ill older patients and their caregivers to ensure that their needs are met during care transitions may reduce the rates of subsequent rehospitalization Objective To evaluate the impact of pharmacotherapeutic counseling on the rates and causes of 30-day post-discharge hospital readmissions and emergency department visits . Setting The study was conducted at the Medical Clinic of University Hospital Dubrava , Zagreb , Croatia . Methods The study included elderly patients prescribed with two or more medications for the treatment of chronic diseases . The patients r and omized into the intervention group received pre-discharge counseling by the clinical pharmacologist about each prescribed medication . The control group received no counseling . Main outcome measures The rates and causes of 30-day postdischarge hospital readmissions and emergency department visits . Medication compliance was also evaluated , using the pill count method . Results A total of 160 patients were r and omly selected for the study . No significant difference was found in the readmission and emergency department visit rates between the intervention and control groups ( p = 0.224 ) . There were 34.9 % more compliant patients in the intervention group . Significantly more non-compliant patients in the control group were readmitted or visited emergency department because of the disease progression ( p = 0.031 ) . In the intervention group , significantly more patients were readmitted or visited emergency department because of an adverse drug reaction ( p = 0.022 ) . Conclusion Pharmacotherapeutic counseling can reduce readmission and emergency department visit rates for disease progression . Improved patient knowledge about adverse drug reactions could be the reason for increased rates of readmissions and emergency department visits due to adverse drug reactions in the intervention group OBJECTIVES To determine if post-discharge telephonic case management ( CM ) reduces emergent hospital readmissions for select high-risk patients . STUDY DESIGN Prospect i ve , r and omized . METHODS We conducted a prospect i ve , r and omized control study of the effect of hospital discharge planning from health plan telephonic case managers on readmissions for high-risk patients . High risk was defined as having an initial discharge major diagnosis of gastrointestinal , heart , or lower respiratory and length of stay of 3 days or more . The intervention group ( N = 1994 ) received telephonic outreach and engagement within 24 hours of discharge and their calls were made in descending risk order to engage the highest risk first . The control group ( N = 1994 ) received delayed telephonic outreach and engagement 48 hours after discharge notification and no call order by risk was applied . Comparison groups had statistically equivalent characteristics at baseline ( P > .05 ) . RESULTS The intent-to-treat 60-day readmission rate for the treatment group was 7.4 % versus 9.6 % for the control group ( P = .01 ) , representing a 22 % relative reduction in all-cause readmissions . Two post hoc assessment s were conducted to identify potential mechanisms of action for this effect and showed that the treatment group had more physician visits and prescription drug fills following initial discharge . CONCLUSIONS Telephonic CM reduces the likelihood of 60-day readmissions for select high-risk patients . This study suggests that prioritizing telephonic outreach to a select group of highrisk patients based on their discharge date and risk severity is an effective case management strategy . Future studies should explore patients ' activity beyond phone calls to further explain the mechanism for readmission reduction PURPOSE Several r and omized trials have found that discharge planning improves outcomes for hospitalized patients . We do not know if adding a clinical nurse specialist ( CNS ) to physician teams in hospitals that already have discharge planning services makes a difference . METHODS In 2 teaching hospitals , patients were r and omly assigned to regular hospital care or care with a clinical nurse specialist . The clinical nurse specialist facilitated hospital care by retrieving preadmission information , arranging in-hospital consultations and investigations , organizing postdischarge follow-up visits , and checking up on patients postdischarge with a telephone call . In-hospital outcomes included mortality and length of stay . Postdischarge outcomes included time to readmission or death , patient satisfaction , and the risk of adverse event . Adverse events were poor outcomes due to medical care rather than the natural history of disease . RESULTS A total of 620 sequential patients were r and omized ( CNS n = 307 , control n = 313 ) , of which 361 were followed after discharge from hospital ( CNS n = 175 , control n = 186 ) . The groups were similar for the probability of in-hospital death ( CNS 9.3 % vs control 9.7 % ) or being discharged to the community ( 58.0 % vs 60.0 % ) . The groups did not differ for postdischarge outcomes including readmission or death ( 21.6 % vs 15.6 % ; P = 0.16 ) or risk of adverse event ( 23.6 % vs 22.8 % ) . Mean [ SD ] patient ratings of overall quality of care on a scale of 10 was higher in the clinical nurse specialist group ( 8.2 [ 2.2 ] vs 7.6 [ 2.4 ] ; P = 0.052 ) . CONCLUSION The addition of a clinical nurse specialist to a medical team improved patient satisfaction but did not impact hospital efficiency or patient safety Remote monitoring ( RM ) of homebound heart failure ( HF ) patients has previously been shown to reduce hospital admissions . We conducted a pilot trial of ambulatory , non-homebound patients recently hospitalized for HF to determine whether RM could be successfully implemented in the ambulatory setting . Eligible patients from Massachusetts General Hospital ( n = 150 ) were r and omized to a control group ( n = 68 ) or to a group that was offered RM ( n = 82 ) . The participants transmitted vital signs data to a nurse who coordinated care with the physician over the course of the 6-month study . Participants in the RM program had a lower all-cause per person readmission rate ( mean = 0.64 , SD ± 0.87 ) compared to the usual care group ( mean = 0.73 , SD ± 1.51 ; P-value = .75 ) although the difference was not statistically significant . HF-related readmission rate was similarly reduced in participants . This pilot study demonstrates that RM can be successfully implemented in non-homebound HF patients and may reduce readmission rates Background Disease-management programmes including patient education have promoted improvement in outcome for patients with Output:	A post hoc regression model showed incremental value in providing comprehensive , postdischarge support to patients and caregivers . AND RELEVANCE Tested interventions are effective at reducing readmissions , but more effective interventions are complex and support patient capacity for self-care . Interventions tested more recently are less effective
MS22504	*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: Individuals with Down 's syndrome ( DS ) have an increased prevalence of periodontal disease compared with otherwise normal , age-matched control groups and other mentally h and icapped patients of similar age distribution . The exaggerated immune-inflammatory response of the tissues can not be explained by poor oral hygiene alone and might be the result of an impaired cell-mediated and humoral immunity and a deficient phagocytic system . As far as the progression and severity of destruction , the oral manifestations of DS patients are consistent with the juvenile periodontitis ( JP ) disease pattern . The purpose of the present study was 1 ) to assess the periodontal clinical and microbiological status of 10 DS patients aged 20 to 31 years ( mean : 26.3 years ) relative to that of 11 patients with cerebral palsy ( CP ) aged 23 to 53 years ( mean : 36 years ) without defective immunological functions , and 2 ) to determine the effect of supragingival plaque control and oral hygiene instruction in these patient groups . Subsequent to the initial examination and a professional tooth cleaning program , clinical and microbiological parameters were monitored over a period of 12 weeks . The clinical examination included the recording of plaque index ( P1 ) , gingival index ( GI ) , probing depth ( PD ) , and clinical attachment level ( CAL ) . Subgingival plaque sample s were always obtained from the same pocket with the highest disease activity ( deepest bleeding site at baseline examination ) in each subject for a morphotype analysis by dark field microscopy and for identification and quantitation of Actinobacillus actinomycetemcomitans , Porphyromonas gingivalis , Prevotella intermedia , Eikenella corrodens , Bacteroides forsythus , Fusobacterium nucleatum , Treponema denticola , and Campylobacter rectus by DNA probes . The results of the baseline examinations demonstrated that DS patients and patients with cerebral palsy had inflamed gingiva associated with a high amount of plaque . The mean probing depth and percentage of sites with probing depth > 4 mm corresponded to age and poor oral hygiene in CP patients . Deep pockets in DS patients demonstrated a high prevalence of periodontal disease compared with age-matched children with mental retardation and non-h and icapped patients . Regarding the young age of onset , the severe destruction of periodontal tissues and pathogenesis of periodontitis in DS patients are consistent with the juvenile periodontitis disease pattern . The missing clinical benefit and alteration of the subgingival flora following supragingival plaque control in DS patients underlined the alteration in the immunological response The effect of local applications of sustained-release delivery polymer containing chlorhexidine as an adjunct to mechanical plaque removal was studied in institutionalized children with Down 's syndrome . Thirty children , ages 8 - 13 , participated in the study . Clinical parameters ( P1I , GI , papillary bleeding ) were recorded and bacterial sample s from selected permanent teeth were collected and processed before and following treatment . Following the registration of clinical findings and collection of plaque , all children had their teeth scaled and polished and were r and omized into three treatment groups of ten subjects each : Subjects in group I had their teeth coated with ethyl cellulose containing chlorhexidine ; those in group II had their teeth coated with placebo polymer and those in group III received no further treatment . Individual oral hygiene habits were not interfered with . The application of the solutions to the respective groups was done every 3 days for 21 days . Chlorhexidine treatment significantly reduced the PLI , GI total aerobic counts and S. viridans counts compared to no treatment . The placebo group showed similar effects to that of the chlorhexidine-treated group except for the total aerobic counts which were not affected . The results suggest that the use of chlorhexidine in a sustained-release dosage form applied to the tooth surfaces may prove useful in the control of plaque and its sequela in children with Down 's syndrome OBJECTIVES To determine the incidence of obstructive sleep apnea syndrome in children aged 2 to 4 years with Down syndrome and to determine parents ' ability to predict sleep abnormalities in this patient population . DESIGN Prospect i ve cohort study . SETTING Tertiary care pediatric referral center . PATIENTS Sixty-five children participating in a 5-year longitudinal study in which the otolaryngologic problems seen in Down syndrome were evaluated . Fifty-six completed overnight polysomnography ( PSG ) between 4 and 63 months of age ( mean age , 42 months ) . INTERVENTIONS Overnight PSG was performed . Parents also completed a question naire regarding their impressions of their child 's sleep patterns before PSG . MAIN OUTCOME MEASURES Polysomnograms were classified as abnormal if the obstructive index was greater than 1 , if the carbon dioxide level was greater than 45 mm Hg for more than two thirds of the study or greater than 50 mm Hg for more than 10 % of the study , and /or if there was unexpected hypoxemia less than 92 % during sleep or repeated intermittent desaturations less than 90 % . We also identified a group of children whose PSGs findings were normal except for an arousal index greater than 10 and were associated with increased work of breathing . RESULTS The PSGs revealed that 57 % of the children had abnormal results and evidence of obstructive sleep apnea syndrome . If we also include an elevated arousal index , 80 % of the PSGs had abnormal results . Sixty-nine percent of parents reported no sleep problems in their children , but in this group , 54 % of PSGs had abnormal results . Of the parents who reported sleep problems in their children , only 36 % had abnormal sleep study results . CONCLUSION Because of the high incidence of obstructive sleep apnea syndrome in young children with Down syndrome , and the poor correlation between parental impressions of sleep problems and PSG results , baseline PSG is recommended in all children with Down syndrome at age 3 to 4 years A sample of 44 adults with severe disabilities completed a r and omized single-blind cross-over study testing chlorhexidine swabbing under various conditions : with/without prior dental prophylaxis , reduced frequency of application ( 2 vs. 5 times per week ) , and prolonged use ( 42 weeks ) . All subjects received therapeutic doses of 10 mL 0.12 % chlorhexidine gluconate ( Peridex , Procter & Gamble ) and 10 mL 0.05 % NaF applied with a Toothette ( Sage Products ) . Clinical effectiveness of chlorhexidine swabbing compared with placebo was previously reported . In the present study , while initial benefits were observed to be independent of dental prophylaxis , significant reductions in periodontal scores were sustained by a combination of dental prophylaxis and swabbing protocol , at reduced frequency of application and over prolonged time . High levels of acceptance and compliance by subjects/caregivers were maintained . Subjects/caregivers reported improvements in dental health as well as in attitude , quality of life , and smile . Chlorhexidine swabbing at maintenance frequency , combined with periodic dental prophylaxis , may offer an effective and pragmatic long-term preventive regimen for persons with disabilities AIM The aim of this single-blind , r and omized , parallel- design ed clinical trial ( RCT ) was to evaluate the clinical and microbiological effects of three sustained-release biodegradable polymers delivered into periodontal pockets following initial periodontal therapy . METHODS Forty-seven patients ( 28 females and 19 males ) with a mean age of 51 years ( range 29 - 71 ) underwent a periodontal examination at baseline ( i.e. Week 0 ) and after 18 weeks . This included the assessment of the Plaque Index ( PlI ) , Bleeding on Probing ( BOP ) , Pocket Probing Depths ( PPD ) and Probing Attachment Levels ( PAL ) at six sites per tooth . Two to 4 months prior to baseline , all subjects had received initial periodontal therapy including motivation , instruction in oral hygiene practice s and full-mouth scaling and root planing . At the treatment appointment ( i.e. Week 2 ) , the patients were r and omly assigned to receive either Atridox trade mark , Elyzol Dental Gel or PerioChip at all residual periodontal pockets with a probing depth > /= 5 mm and concomitant BOP . In accordance with the manufacturer 's recommendations , Elyzol Dental Gel was applied for a second time 7 days later . In addition to the clinical evaluation , subgingival microbiological sample s were collected prior to treatment ( i.e. Week 2 ) and at Weeks 4 and 18 . Analysis of variance/covariance was used to evaluate changes from baseline to Week 18 for the clinical parameters . RESULTS Between the baseline and 18-week examinations , subjects treated with Atridox showed a significantly greater gain in mean PAL of 0.33 mm + /- 0.09 ( SD ) than subjects treated with Elyzol Dental Gel [ 0.03 mm + /- 0.09 (SD)](p = 0.03 ) . However , the gain in PAL of 0.16 mm + /- 0.10 ( SD ) found after PerioChip application did not differ significantly from that obtained following the application of Atridox(p = 0.27 ) . Of the sites treated with Atridox , 42 % gained > /= 1 mm PAL and 9 % > /= 2 mm PAL as opposed to the sites treated with Elyzol Dental Gel , in which 34 % gained > /= 1 mm PAL and 8 % gained > /= 2 mm PAL . Of the sites treated with PerioChip , 36 % gained > /= 1 mm and 6 % gained > /= 2 mm PAL following a completed initial periodontal therapy . CONCLUSIONS The application of the three biodegradable sustained release devices tested following initial periodontal therapy result ed in a statistically significant gain in mean PAL for AtridoxTM and a significant reduction in PPD for all three devices during the study period . Furthermore , when sites treated with Atridox were compared with sites treated with Elyzol , a significant difference in mean PAL gain ( 0.3 mm ) was observed BACKGROUND Individuals with Down 's syndrome ( DS ) differ in their oral condition compared with the healthy population . Periodontal disease in persons with DS under the age of 30 years is very high . Immune deficiencies are also present . For dental practitioners it is difficult to decide on a particular course of treatment . In this study , patients with DS were selected in order to 1 ) evaluate the effectiveness of surgical and non-surgical periodontal therapies and 2 ) assess their immunological status . METHODS The population consisted of 14 DS patients ( 14 to 30 years old ) . Surgical and non-surgical periodontal therapies were compared in a split-mouth design . Clinical measurements of plaque index ( PI ) , gingival index ( GI ) , probing depth ( PD ) , and clinical attachment levels ( CAL ) were taken at baseline , posttreatment , 6 months , and 1 year . Immunomodulatory activity of neutrophils was analyzed in vitro by chemotaxis ( Boyden migration chamber ) , phagocytic activity , and production of super-oxide anion ( NBT reduction ) tests and compared between DS patients and healthy controls . RESULTS Both surgical and non-surgical therapies showed a significant improvement in all the clinical parameters compared to baseline . There were no differences between surgical and nonsurgical therapy in PI or GI . There was a significant PD reduction with the non-surgical therapy at 1 to 3 mm PD . However in PD > 3 mm the surgical therapy , although not statistically significant , showed better results . Neutrophil chemotaxis , phagocytic activity , and production of super-oxide anion were significantly decreased in the DS patients . CONCLUSIONS After a year , both surgical and non-surgical therapies have similar periodontal clinical improvement in DS patients . There is partial impairment of immunological functions in DS individuals which does not seem to affect the clinical response to therapy OBJECTIVE To evaluate the mechanical and chemical control of dental biofilm in patients with Down syndrome , using different experimental dentifrices . MATERIAL AND METHODS Forty institutionalized children between ages 7 and 13 years in the mixed dentition phase participated in this study . An experimental cross-over , blind clinical trial was used , having the following protocol s : fluori date d dentifrice ( protocol G1 ) ; fluori date d dentifrice + chlorhexidine ( protocol G2 ) ; fluori date d dentifrice + chlorhexidine + plaque-disclosing agent ( protocol G3 ) ; and fluori date d dentifrice + plaque-disclosing agent ( protocol G4 ) . Each experimental stage lasted 10 days with a 15-day washout . The evaluated parameters were Plaque Index and gingival bleeding . RESULTS The initial clinical conditions between each stage were similar . Statistical differences were observed ( P < 0.001 ) for the clinical conditions evaluated before and after the treatments . The dentifrices containing plaque-disclosing agent , irrespective of their association with chlorhexidine , produced a greater reduction in the final plaque index . As for gingival bleeding , the dentifrice containing erythrosine and the one containing chlorhexidine produced similar results . The dentifrice containing an association of chlorhexidine and erythrosine gave the best results . CONCLUSION With the methodology employed , it was possible to conclude that the combination of drugs ( chlorhexidine , fluorine and erythrosine ) within one dentifrice can be useful in controlling dental biofilm and in the reduction of gingival bleeding BACKGROUND Periodontal disease in Down 's syndrome ( DS Output:	The results demonstrated the importance to introduce youngest DS patients in preventive programs , as well as participation of parents , caregivers or institutional attendants in supervising/performing oral hygiene . In studies with higher frequency of attendance , all age groups presented superior preventive and therapeutic results , irrespective of the therapeutic approach used ( surgical/nonsurgical/periodontal care program ) . The important factors for reducing periodontal parameters were the frequency of the appointments and association with chlorhexidine/plaque disclosing agents as adjuvant treatment . This systematic review demonstrated that early introduction in periodontal care , participation of parents/caregivers/institutional attendants , frequency of attendance and association with chemical adjuvants ( independently of the periodontal treatment adopted ) seems to improve periodontal outcomes in preventive and periodontal treatment of DS patients .
MS22505	*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 open-label study was design ed to determine the extent of histological resolution of gastritis induced by Helicobacter pylori infection 4–5 weeks after successful eradication of the infection . Eradication was achieved using a triple therapy regimen consisting of a twice daily dose of pantoprazole 40 mg , clarithromycin 500 mg , and amoxicillin 1,000 mg taken for 1 week only . No other medications were given thereafter . Four biopsies were processed for histological examination of each patient , two from the antral and two from the corporeal mucosa , first at the start of the study and then again 4 weeks after cessation of the medication trial . Scoring for H. pylori colonization and the severity of gastritis was determined for each patient according to the Sydney system . 53 of 57 patients in this study had their H. pylori infection successfully eradicated by the regimen mentioned and could be histologically evaluated . According to the severity of gastritis in the antral mucosa , patients were studied in 3 groups : mild , moderate and severe gastritis . 17 of 19 cases with mild gastritis showed complete resolution of the inflammation , with residual inflammatory changes persisting in 2 cases only . 22 of the 26 cases with moderate gastritis showed almost complete recovery except for minor residual inflammatory changes as judged by irregularity of intracytoplasmic mucine storage . Persistent residual inflammatory changes in the lamina propria were detected in 4 cases . Of the 8 cases with severe gastritis 5 showed subsidence of the inflammatory changes , but the mucosa in these cases revealed some scarring , distortion of the gl and ular epithelium and atrophy . In 3 cases residual inflammation persisted . Conclusion : One-week therapy with a twice daily dose of pantoprazole 40 mg , clarithromycin 500 mg and amoxicillin 1,000 mg , used to eradicate H. pylori causing active inflammation of the gastric mucosa , has led to subsidence of the acute inflammatory changes in all the cases with residual inflammation persisting in 17 % . Severe gastritis may cause irreparable damage to the gastric mucosa . The density of H. pylori colonization does not appear to be related to the severity of gastritis , nor to the successful eradication achieved Experience with proton pump inhibitor‐based triple therapy is predominantly with omeprazole‐containing regimens Background : Previous studies have shown that one‐week triple therapy consisting of omeprazole , clarithromycin and amoxycillin may cure Helicobacter pylori infection in the vast majority of patients . The present study was design ed to test the hypothesis that a triple therapy with pantoprazole , clarithromycin and amoxycillin cures the infection in 80 % of duodenal ulcer patients infected with H. pylori BACKGROUND Short-term , low-dose triple regimens composed of proton-pump inhibitors ( PPI ) and two antibiotics are the current gold st and ard therapy for cure of Helicobacter pylori infection . To date , the effect of PPI pretreatment on eradication outcome is not known . The aim of this study was to evaluate the influence of pretreatment with pantoprazole on the efficacy of an ensuing triple therapy . METHODS In this open , r and omized , monocenter , parallel group comparison , 107 patients with duodenal ulcer or functional dyspepsia were assigned to receive one of the following treatment regimens : a 7-day triple therapy with pantoprazole , 40 mg bid ; clarithromycin , 250 mg bid ; and metronidazole , 400 mg bid , which was either preceded or followed by a 7-day therapy with pantoprazole , 40 mg ( P-PCM or PCM-P ) . Assessment of H. pylori status was performed by a biopsy urease test and 13C urea breath test at the initial visit and 13C urea breath test at all follow-up visits . RESULTS The 7-day pantoprazole pretreatment result ed in a significant decline of the delta values of the 13C urea breath test . H. pylori infection was cured in 47 of 52 intention-to-treat patients of the P-PCM group ( 90 % ; 95 % confidence interval , 79 - 97 % ) and in 46 of 53 of the PCM-P group ( 87 % ; 95 % confidence interval , 75 - 95 % ) . CONCLUSIONS Pretreatment with pantoprazole suppresses H. pylori but does not impair the efficacy of a consecutive short-term , low-dose triple therapy Triple therapy with proton pump inhibitor , clarithromycin and amoxicillin has recently been proposed in Maastricht as first‐line treatment for H. pylori infection The aim of this study was to compare the efficacy of two different 5-day proton pump inhibitor (PPI)-based triple therapies for Helicobacter pylori (Hp)-positive duodenal ulcers ( DUs ) . Eighty-four patients received pantoprazole ( Pan ) 80 mg O.D. ( once daily ) for 1 week ; 88 patients received omeprazole ( Ome ) 40 mg O.D. for 1 week . Patients of both groups received clarithromycin ( Cla ) 500 mg B.I.D. ( twice daily ) and amoxicillin ( Amo ) 1 g B.I.D. for 5 days . All of them were clinical ly and endoscopically investigated before enrollment ( T0 ) and at 1 ( T1 ) , 6 ( T2 ) , 12 ( T3 ) , and 18 months ( T4 ) after the end of the therapy . Hp status was determined by rapid urease test and by histology . At T1 , we observed ulcer healing in 87.5 % of the patients and Hp eradication in 83.7 % of the Pan group ( per protocol [ PP ] ) . In the Ome group , ulcer healing was noticed in 95.1 % and Hp eradication in 95.1 % ( PP ) . We found no statistical differences between the groups ( PP ) . At the end of the follow-up , we found a healing rate of 100 % both in the Pan group and in the Ome group ; an eradication rate of 98.4 % and 100 % was observed in the Pan group and in the Ome group , respectively . We found no statistical differences between the groups ( PP ) . Hp eradication was associated with an improvement in the grade of gastritis at T1 , remaining unchanged until T4 . In conclusion , the efficacy of the Pan treatment was similar to the Ome treatment OBJECTIVES : A novel rifabutin-based therapy is able to cure Helicobacter pylori infection in most patients who have failed eradication after st and ard proton pump inhibitor (PPI)-based triple therapy . We compared this regimen with the quadruple therapy . METHODS : A total of 135 patients were r and omized into three groups who were treated for 10 days with pantoprazole 40 mg b.i.d . , amoxycillin 1 g b.i.d . , and rifabutin 150 mg o.d . ( RAP150 group ) , or 300 mg o.d . ( RAP300 group ) , and pantoprazole 40 mg b.i.d . , metronidazole 250 mg t.i.d . , bismuth citrate 240 mg b.i.d . , and tetracycline 500 mg q.i.d . ( QT group ) . Before therapy , patients underwent endoscopy with biopsies for histology , culture and antibiotic susceptibility tests . H. pylori eradication was assessed by the 13C-urea breath test . RESULTS : On intention-to-treat analysis , eradication rates ( with 95 % confidence intervals [ CI ] ) were 66.6 % ( 53–80 % ) in the RAP150 and QT groups , respectively , and 86.6 % ( 76–96 % ) in RAP300 group ( p < 0.025 ) . Most patients harboring metronidazole- and clarithromycin-resistant strains were eradicated at an equal rate by each of the three regimens . Side effects were observed in 9 % and 11 % of rifabutin-treated patients , and in 47 % of those on quadruple therapy ( p < 0.0001 ) . CONCLUSIONS : In patients who failed st and ard eradicating treatments , a 10-day course of rifabutin with pantoprazole and amoxycillin is more effective and well tolerated than the quadruple therapy Azithromycin is an acid‐stable macrolide that achieves remarkably high concentrations in gastric tissue , persisting above the MIC90 for Helicobacter pylori over a period of 5‐days , after a single 500 mg oral dose In a prospect i ve study 27 patients ( 13 women , 14 men ; mean age 62 [ 45 - 83 ] years ) with Helicobacter ( H. ) pylori associated disease received over 7 days pantoprazole ( 40 mg twice daily ) , clarithromycin ( 500 mg twice daily ) and metronidazole ( 500 mg twice daily ) . Six patients had gastric ulcer , 4 duodenal ulcer , 4 erosive gastritis , 6 erosive duodenitis and 7 had H. pylori-positive functional dyspepsia . Pre-treatment oesophago-gastro-duodenoscopy was combined in 4 patients with antral and in 4 others with body-of-stomach biopsies to demonstrate H , pylori ( urease test , specific culture and histology ) . The H. pylori status was checked with the 13C-urea breath test 4 weeks after the end of treatment . In addition , 9 patients with peptic ulcer were examined endoscopically at least 2 weeks after onset of the treatment to check for any healing of the ulcers , 25 of the patients completed the study according to the protocol . The H. pylori eradication rate was 100 % ( 25 of 25 patients ) , while the " intention to treat " analysis gave a rate of 92.6 % ( 25 of the 27 patients ) . The peptic ulcers were found to be healed in all 9 patients who had been endoscoped . One woman developed a reversible stomatitis , but the drug treatment did not have to be stopped . -These findings indicate that short-term triple treatment in the described manner is efficacious in curing H. pylori infection and any peptic ulcer . It is thus a highly promising treatment of H. pylori-associated diseases BACKGROUND / AIMS The relationship between functional dyspepsia , H. pylori infection and chronic gastritis is controversial . Our aims were 1 ) To determine the prevalence of symptoms and the degree of association between symptoms and histopathological findings in different topographical gastric regions in patients with functional dyspepsia and H. pylori infection ; 2 ) To determine the effect of eradication treatment on functional dyspepsia symptoms . METHODOLOGY Prospect i ve r and omized study . 251 consecutive patients with dyspepsia ( 141 women and 110 men ) , mean age 48.08 , SD 16.68 ( without ulcer , gastric malignancy or reflux esophageal disease as determined by endoscopy ) , and with H. pylori infection , underwent upper endoscopy accompanied by the obtaining of 6 biopsies ( cardia , corpus , antrum ) at baseline , 3 and 6 months after treatment ( pantoprazole 40 mg , once daily , amoxycillin 100 mg b.i.d . , clarithromycine 500 mg b.i.d . ) . Inflammation , activity , H. pylori presence and other mucosal alterations were evaluated semi-quantitatively according to the Sydney system , before treatment and 6 months following treatment . An interview that was carried out before , and 6 months following the treatment , determined seven symptoms ( scored as 0 - 3 ) ; epigastric burning and pressure , pain after meal , nausea , vomiting , bloating and belching , pain on empty stomach and anorexia . 95 % confidence intervals were calculated for mean values of the symptoms and histological findings . The association between symptoms and histological findings was determined by the Kendall tau-b ( K tau-b ) . Using the t test on a 5 % level of significance we tested the null hypothesis that symptoms and histological findings were independent variables . RESULTS The effectiveness of eradication after 3 months was 87.3 % and after 6 months 92.0 % . Reinfection rate after 6 months was 6.4 % and the overall failure of eradication was 1.6 % . Significant decline of chronic inflammation , activity and H. pylori was found in cardia , corpus and antrum ( P = 0.001 ) . Gl and ular atrophy was found to be lower in corpus and antrum ( P = 0.001 ) , whereas in cardia an increase was found . Intestinal metaplasia remained unchanged in all gastric regions , whereas a higher degree of foveolar hyper Output:	Pantoprazole achieves similar cure rates to those of omeprazole and lansoprazole when co-prescribed with antibiotics for the eradication of H. pylori infection
MS22506	*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 recent clinical studies , clindamycin phosphate cream administered intravaginally has been shown to be efficacious in the treatment of bacterial vaginosis ( BV ) . In support of the safety profile for this dosage form , a study assessing the systemic absorption of clindamycin was undertaken in five BV patients and six healthy volunteers who were dosed with 5 mL ( 100 mg ) clindamycin phosphate 2 % cream intravaginally once daily in the evening for 7 days . Two weeks later , a single 100 mg dose of clindamycin phosphate sterile solution was administered as a 4 min iv infusion . Serial blood sample s were collected on days 1 , 4 , and 7 after dosing with the cream and over a 16 h period after the iv treatment . Clindamycin concentrations in serum sample s were assayed by capillary gas chromatography . After treatment with the cream , steady-state serum clindamycin concentrations were reached by 24 h in all but one subject in each group . Mean absolute bioavailability was 2.7%-4.3 % in the BV group and 2.7%-4.7 % in the healthy group . These results indicate that systemic exposure to clindamycin from intravaginal administration of clindamycin phosphate cream is minimal OBJECTIVES : To determine whether intravaginal clindamycin cream reduces the incidence of abnormal pregnancy outcome in women with abnormal vaginal microbial flora grade d as intermediate or BV and to investigate the effect of the antibiotic on vaginal microbial flora . METHODS : A prospect i ve cohort study of pregnant women in an antenatal clinic of a district general hospital . The subjects were 268 women who had abnormal vaginal microbial flora at first clinic visit by examination of a Gram-stained vaginal smear and 34 women with a normal vaginal flora . Two hundred and thirty-seven women were evaluable . Women with abnormal Gram-stained smears ( grade d as II or III ) on clinic recall were r and omised to receive treatment ( intravaginal clindamycin cream ) or placebo and followed to assess outcome of pregnancy , vaginal flora , and detection of Mycoplasma hominis and Ureaplasma urealyticum after treatment . RESULTS : Abnormal outcomes of pregnancy were not significantly different in treated and placebo groups by Chi square ( P = 0.2 ) . However , women with grade III flora responded better to clindamycin than women with grade II flora by numbers of abnormal outcomes ( P = 0.03 ) and return to normal vaginal flora ( P = 0.01 ) ( logistic regression analysis model ) . This may be due to differences in vaginal bacterial species in these grade s. Women whose abnormal vaginal flora had spontaneously returned to normal on follow-up and were therefore not treated ( revertants ) had as many abnormal outcomes as placebos suggesting that damage by abnormal bacterial species occurred early in pregnancy . CONCLUSIONS : Gram-stain screening distinguishing grade II from grade III flora may be helpful in prescribing treatment other than clindamycin for women with grade II flora . Earlier diagnosis and treatment may be more effective in preventing an abnormal outcome , possibly as soon as pregnancy is diagnosed or even offered as a pre-conception screen Abstract Objective To evaluate whether a screening strategy in pregnancy lowers the rate of preterm delivery in a general population of pregnant women . Design Multicentre , prospect i ve , r and omised controlled trial . Setting Non-hospital based antenatal clinics . Participants 4429 pregnant women presenting for their routine prenatal visits early in the second trimester were screened by Gram stain for asymptomatic vaginal infection . In the intervention group , the women 's obstetricians received the test results and women received st and ard treatment and follow up for any detected infection . In the control group , the results of the vaginal smears were not revealed to the caregivers . Main outcome measures The primary outcome variable was preterm delivery at less than 37 weeks . Secondary outcome variables were preterm delivery at less than 37 weeks combined with different birth weight categories equal to or below 2500 g and the rate of late miscarriage . Results Outcome data were available for 2058 women in the intervention group and 2097 women in the control group . In the intervention group , the number of preterm births was significantly lower than in the control group ( 3.0 % v 5.3 % , 95 % confidence interval 1.2 to 3.6 ; P = 0.0001 ) . Preterm births were also significantly reduced in lower weight categories at less than 37 weeks and ≤ 2500 g. Eight late miscarriages occurred in the intervention group and 15 in the control group . Conclusion Integrating a simple infection screening programme into routine antenatal care leads to a significant reduction in preterm births and reduces the rate of late miscarriage in a general population of pregnant women OBJECTIVE To assess the ability of clindamycin vaginal cream to reduce the incidence of preterm birth in women with abnormal genital tract flora in the second trimester of pregnancy . METHODS This was a r and omized , double-blind , placebo-controlled , tricenter study . A total of 409 women with abnormal genital tract flora on Gram stain of vaginal secretions at 13–20 weeks ' gestation were r and omized to receive a 3-day course of clindamycin vaginal cream or placebo . Those women who still had abnormal vaginal flora 3 weeks later received a 7-day course of the original study drug ( ie , either clindamycin vaginal cream or placebo as per original r and omization ) . The primary outcome measure was the incidence of preterm birth . RESULTS There was a statistically significant reduction in the incidence of preterm birth in the clindamycin vaginal cream group ( 4 % ) compared with placebo ( 10 % ) ( P < .03 ) . Significantly more babies born preterm ( 63 % ) required admission to the neonatal intensive care unit compared with term infants ( 4 % ) ( P < .001 ) . CONCLUSION A 2 % clindamycin vaginal cream , when compared with placebo administered to women with abnormal genital tract flora before 20 weeks ' gestation , can reduce the incidence of preterm birth by 60 % and hence the need for neonatal intensive care OBJECTIVE Our purpose was to analyze ( 1 ) the effects of prevalent lower reproductive tract infections and ( 2 ) the effect of systematic diagnosis and treatment to reduce risks of early pregnancy loss ( < 22 weeks ) , preterm premature rupture of membrances , and overall preterm birth . STUDY DESIGN A prospect i ve , controlled treatment trial was conducted on 1260 women . During the first 7 months of the program ( observation , phase I ) , women were examined at initiation of prenatal care for a panel of lower genital tract microorganisms and bacterial vaginosis . Women were followed up with reexaminations at 22 to 29 weeks and after 32 weeks ' gestation . The recommended treatments of the Centers for Disease Control ( i.e. , 300 mg of clindamycin orally twice daily for 7 days for bacterial vaginosis ) were used for infected women during the second 8 months of the study ( treatment , phase II ) . Data were analyzed according to intent to treat by means of univariate and multivariate methods . RESULTS Overall , presence of bacterial vaginosis ( 32.5 % ) at enrollment was associated with pregnancy loss at < 22 weeks ' gestation ( relative risk 3.1 , 95 % confidence interval 1.4 to 6.9 ) . Among women in the observation phase bacterial vaginosis was associated with increased risk of both preterm birth ( relative risk 1.9 , 95 % confidence interval 1.2 to 3.0 ) and preterm premature rupture of membranes ( relative risk 3.5 , 95 % confidence interval 1.4 to 8.9 ) . Within this population ( phase I ) 21.9 % of preterm birth overall ( 43.8 % premature rupture of membranes ) is estimated as attributable to bacterial vaginosis . Among women with bacterial vaginosis phase II ( treatment ) was associated with reduced preterm birth ( relative risk 0.5 , 95 % confidence interval 0.3 to 0.9 ) ; there was a similar reduction for women with preterm premature rupture of membranes ( relative risk 0.5 , 95 % confidence interval 0.2 to 1.4 ) . Women with both bacterial vaginosis and trichomoniasis were at highest risk of preterm birth ( 28 % ) ; treatment of both conditions ( phase II ) reduced preterm birth ( 17 % ) but did not eliminate this risk . Earlier patient enrollment and oral antibiotic treatment were associated with reduced preterm birth . CONCLUSIONS This prospect i ve , controlled trial confirms that the presence of bacterial vaginosis is associated with increased risks of pregnancy loss at < 22 weeks , preterm premature rupture of membranes , and preterm birth . Orally administered clindamycin treatment is associated with a 50 % reduction of bacterial vaginosis-linked preterm birth and preterm premature rupture of membranes . Women at risk for preterm birth or preterm premature rupture of membranes because of bacterial vaginosis or common genital tract infections should be screened , treated , reevaluated for cure , and re-treated if necessary Fourteen of 28 Trichomonas vaginalis isolates collected from patients in Guangzhou , China from 2003 to 2004 were found to be naturally infected with Mycoplasma hominis , as determined by PCR using specific primers . In vitro metronidazole sensitivity assay of the 28 isolates revealed four displaying low susceptibility [ minimum lethal concentration (MLC)=∼13–25 μg/ml ] and another four displaying high resistance ( MLC=50–100 μg/ml ) . The overwhelming majority of these resistant isolates ( 7/8 ) were mycoplasma-infected . The mean of MLCs of mycoplasma-infected isolates is ∼10-fold higher than the mean of noninfected isolates ( p=0.029 ) . Sequence analyses of PCR-amplified small subunit – large subunit rRNA interspacer regions ( ITS1/5.8S/ITS2 ) revealed that 23 of the 28 sample s are identical , the remaining five being separable into two groups , each with a single point mutation . These internal transcribed spacer sequence variants are associated neither with mycoplasma infection nor with drug resistance . In contrast , r and om amplified polymorphic DNA analyses of DNAs using 10 different primers showed that the drug-resistant isolates are clustered together in association with mycoplasma infection , albeit more loosely . Taken together , the results obtained from this study suggest that in vitro metronidazole resistance of T. vaginalis is related to mycoplasma infection of this protozoan BACKGROUND The ORACLE II trial compared the use of erythromycin and /or amoxicillin-clavulanate ( co-amoxiclav ) with that of placebo for women in spontaneous preterm labour and intact membranes , without overt signs of clinical infection , by use of a factorial r and omised design . The aim of the present study --the ORACLE Children Study II -- was to determine the long-term effects on children after exposure to antibiotics in this clinical situation . METHODS We assessed children at age 7 years born to the 4221 women who had completed the ORACLE II study and who were eligible for follow-up with a structured parental question naire to assess the child 's health status . Functional impairment was defined as the presence of any level of functional impairment ( severe , moderate , or mild ) derived from the mark III Multi-Attribute Health Status classification system . Educational outcomes were assessed with national curriculum test results for children resident in Engl and . FINDINGS Outcome was determined for 3196 ( 71 % ) eligible children . Overall , a greater proportion of children whose mothers had been prescribed erythromycin , with or without co-amoxiclav , had any functional impairment than did those whose mothers had received no erythromycin ( 658 [ 42.3 % ] of 1554 children vs 574 [ 38.3 % ] of 1498 ; odds ratio 1.18 , 95 % CI 1.02 - 1.37 ) . Co-amoxiclav ( with or without erythromycin ) had no effect on the proportion of children with any functional impairment , compared with receipt of no co-amoxiclav ( 624 [ 40.7 % ] of 1523 vs 608 [ 40.0 % ] of 1520 ; 1.03 , 0.89 - 1.19 ) . No effects were seen with either antibiotic on the number of deaths , other medical conditions , behavioural patterns , or educational attainment . However , more children whose mothers had received erythromycin or co-amoxiclav developed cerebral palsy than did those born to mothers who received no erythromycin or no co-amoxiclav , respectively ( erythromycin : 53 [ 3.3 % ] of 1611 vs 27 [ 1.7 % ] of 1562 , 1.93 , 1.21 - 3.09 ; co-amoxiclav : 50 [ 3.2 % ] of 15 Output:	We conclude that inappropriate antibiotics used in inappropriate women at inappropriately late gestations do not reduce preterm birth . Conversely , a focused systematic review /meta- analysis , which targeted the use of clindamycin before 22 weeks gestation , in women with objective evidence of abnormal genital tract flora , demonstrated that clindamycin produced a significant decrease in late miscarriage and preterm birth
MS22507	*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 double-blind , parallel-group , multicenter study , 169 patients with symptoms of maxillary sinusitis but without radiographically confirmed empyema ( pus ) were r and omly assigned to receive either 500 mg azithromycin once daily for 3 days ( 87 patients ) or placebo daily for 3 days ( 82 patients ) . Nasal secretion , maxillary tenderness and pain , nasal obstruction , general malaise , and hyposmia were assessed at the start of the study and on days 4 , 11 , and 25 of treatment . After 11 days 58 % of the patients in the azithromycin group were cured versus 31 % in the placebo group ; after 25 days the cure rate was 79 % versus 67 % , respectively . When both cure and improvement were considered , the corresponding figures after day 25 were 90 % and 88 % , respectively . Adverse events , predominantly gastrointestinal , occurred in 24 ( 27 % ) of the azithromycin-treated patients and in 15 ( 18 % ) of those treated with placebo , but the difference was not statistically significant . There was a difference in efficacy in favor of azithromycin in the treatment of rhinitis with symptoms of maxillary sinusitis but without radiological signs of empyema ( pus ) . Antibiotics should only be used to alleviate symptoms in patients with moderate to severe symptoms , as the results after 25 days for both improvement and cure are equal . In the treatment of acute rhinitis with symptoms and signs of maxillary sinusitis but without empyema , treatment with azithromycin seems to result in a better cure rate after 10–12 days when compared with placebo OBJECTIVE To compare the efficacy of amoxicillin vs placebo in patients with an acute upper respiratory tract infection and purulent rhinorrhea . STUDY DESIGN Double-blind r and omized placebo-controlled trial . POPULATION The 416 patients included from 69 family practice s were 12 years or older , presenting with acute upper respiratory complaints , and having a history of purulent rhinorrhea and no signs of complications of sinusitis . OUTCOMES MEASURED Therapy success ( disappearance of symptoms that most greatly affected the patient 's health ) at day 10 and duration of general illness , pain , and purulent rhinorrhea . RESULTS Therapy was successful in 35 % of patients with amoxicillin and in 29 % of patients with placebo ( relative risk [ RR ] 1.14 , 95 % confidence interval [ CI ] , 0.92 - 1.42 ) . There was no effect on duration of general illness or pain . Duration of purulent rhinorrhea was shortened by amoxicillin ( 9 days vs 14 for clearing of purulent rhinorrhea in 75 % of patients ; P = .007 ) . Diarrhea was more frequent with amoxicillin ( 29 % vs 19 % , RR 1.28 , 95 % CI , 1.05 - 1.57 ) . No complications were reported . One patient ( 0.5 % ) receiving amoxicillin and 7 ( 3.4 % ) receiving placebo discontinued trial therapy because of exacerbation of symptoms ( RR 0.25 , 95 % CI 0.04 - 1.56 , P = .07 ) . All 8 patients recovered with antibiotic therapy . CONCLUSIONS Amoxicillin has a beneficial effect on purulent rhinorrhea caused by an acute infection of the nose or sinuses but not on general recovery . The practical implication is that all such patients , whatever the suspected diagnosis , can be safely treated with symptomatic therapy and instructed to return if symptoms worsen In this double-blind study of 60 infants with undifferentiated respiratory diseases , antibiotics seemed of no benefit in shorten ing the median duration of illness or in preventing secondary complications . The conclusion is drawn that the danger of complications from the antibiotics them selves is greater than the good which many physicians believe that antibiotics produce in such diseases preparation , and phenylephrine plus nitrofurazone 0.02 per cent solution t as the test preparation . Each was dispensed in a plastic dropping container marked only with a code number ; neither patient nor physician knew to which group the patient had been assigned . All 100 patients ---541 in each group-were from a general practice in pediatrics and had purulent rhinitis . Each patient was provided A double-blind r and omized controlled trial of amoxycillin , co-trimoxazole , and placebo was conducted on 197 children presenting with presumed viral respiratory infections . Routine throat swabs were taken to exclude streptococcal diseases . The three disease categories studied -- nasopharyngitis , pharyngotonsillitis , and bronchitis ( including laryngotracheobronchitis)--showed a generally similar pattern of resolution irrespective of treatment . Nevertheless , seven out of 66 children receiving placebo were withdrawn from the trial with unremitting symptoms or complications thought to require antimicrobial treatment . Only two of 56 children receiving amoxycillin and none of 75 receiving co-trimoxazole were withdrawn . Three other children receiving amoxycillin and three receiving placebo were seen during the trial but further treatment was not thought to be necessary . Thus the return consultation rate in children receiving placebo therapy was 15 % compared with 4 % for those receiving antimicrobial treatment . Antimicrobial treatment was associated with less nasal discharge on the eighth day of treatment . Placebo treatment allowed an earlier return to normal activity . There was a high incidence of possible side effects on all regimens including placebo . It is concluded that the benefits of antimicrobial treatment in presumed viral respiratory infections are marginal , and they should not be routinely prescribed for these conditions Purulent nasal discharge ( discharge that is thick , opaque and colored ) is a common clinical symptom in pediatrie patients . Although it may occur at any age it is probably most problematic and most common in children between birth and 2 to 3 years of age . This article review s the differential diagnosis , evaluation and management of purulent nasal discharge in children The benefits of antibiotic treatment and a nasopharyngeal culture in children with longst and ing cough were analysed in a prospect i ve r and omized open study . Clinical ly suspected pertussis was excluded . Of 40 children given erythromycin for 7 days , 35 ( 88 % ) recovered in one week , compared with 17/47 ( 36 % ) untreated ( p < 0.0001 ) . Erythromycin eliminated Moraxella catarrhalis from the nasopharynx in 21/31 children ( 68 % ) , compared with spontaneous disappearance in 7/35 ( 20 % ) untreated controls ( p < 0.001 ) . Purulent bronchitis or otitis media occurred in 2 children ( 5 % ) in the treatment group and in 21 ( 45 % ) in the control group ( p < 0.01 ) . To evaluate the clinical role of isolated pathogens , the 47 untreated subjects were studied . Seven of 35 children harbouring M. catarrhalis recovered , compared with 8/12 in whom this bacterium was absent ( p < 0.01 ) . No correlation was found between the isolation of Haemophilus influenzae or Streptococcus pneumoniae and the clinical outcome . Children with persistent cough > 10 days may benefit from erythromycin treatment . M. catarrhalis in the nasopharynx indicates prolonged symptoms and increased risk of bacterial complications Effectiveness and clinical tolerance of the tixocortol-neomycin combination ( Pivalone-Neomycin nasal suspension ) used as monotherapy were evaluated in a double-blind placebo-controlled study ( placebo : vehicle i.e. , N-cetylpyridinium chloride , sodium chloride , sodium hydroxide solution , benzyl alcohol , purified water , monosodium phosphate ) in 211 pediatric patients ( aged 6 months to 8 years ) with uncomplicated acute rhinopharyngitis . After seven days therapy , improvement in symptoms of acute rhinopharyngitis , especially rhinorrhea and nocturnal cough , was greater in the tixocortol-neomycin group . Physical evaluation documented significant improvements in local superinfection with disappearance of mucopurulent nasal secretions and posterior drip . Locoregional outcome , evaluated on severity of infectious complications and antibiotic use , was also more favorable in the tixocortol-neomycin group . These results , together with the good clinical tolerance of the study drug , demonstrate the value of single-drug therapy with this local corticosteroid-neomycin combination in children with uncomplicated acute rhinopharyngitis . They confirm that local administration of corticosteroids to combat inflammatory phenomena is useful not only in the well-recognized lower respiratory tract indications ( asthma , respiratory syncitial virus infections ) but also in nasal diseases ( rhinitis ) AIM To assess General Practice ( GP ) description and management of upper respiratory tract infections ( URTI ) , including conditions under which they prescribe antibiotics . METHOD A telephone survey of a r and omised sample of Auckl and GPs . RESULTS There was a 61 % response rate . 82 of the 100 GPs interviewed agreed that most patients presenting with URTI expected antibiotics . Persistent symptoms and indication of specific infection ( tonsillitis , otitis media , sinusitis , pharyngitis , purulent sputum ) were common reasons for prescribing . Patients travelling overseas , expecting or requesting antibiotics and prior use of over-the-counter ( OTC ) medications increased antibiotic prescribing-rates . Most GPs ( 95 % ) issued as-needed prescriptions on occasion ; 13 % did this often . Amoxicillin and amoxicillin/clavulanic acid were most commonly used . Despite wide-ranging antibiotic use for URTI ( 0 to 90 % ) , only 6 % of GPs felt they prescribed more antibiotics than others . CONCLUSIONS The results suggest over-prescription is common-place , but use of as-needed prescriptions to reduce antibiotic use is encouraging . Exploration of patient expectations in the consultation may assist in decreasing prescribing rates The clinical responses of children with upper respiratory infections to 1 of 3 treatment regimens ( tetracycline , penicillin , and placebo ) were evaluated in relation to the bacterial and viral pathogens cultured from nasopharyngeal swabs . The 3 treatment groups were similar in size and in the frequency and type of pathogens recovered . The groups did not differ in their response to the treatment regimens in terms of mean duration of fever , failure to improve , the development of complications , or the persistance of bacterial pathogens in the nasopharynx This preliminary study evaluated the effectiveness of enteric-coated erythromycin in the treatment of adults with nonstreptococcal pharyngitis . Twenty-six patients , aged 12 or older , with nonstreptococcal pharyngitis were r and omly assigned in a double-blind fashion to receive either enteric-coated erythromycin or placebo for 10 days . Each day the patients rated the soreness of their throats and how sick they felt . The use of erythromycin appeared to decrease the median number of days for the feeling of sickness to improve ( two days versus four days , P less than .01 ) as well as to decrease the median number of days for the feeling of sickness to resolve ( three- and -a-half days versus five days , P less than .05 ) . This apparent improvement in sickness occurred even though there was no significant decrease in the soreness of the throat in patients treated with erythromycin compared to those patients treated with placebo . Treatment with enteric-coated erythromycin appeared to shorten the time until improvement in this group of adults with nonstreptococcal pharyngitis Abstract The recommended treatment for mild acute respiratory infections ( ARI ) in children is supportive care only , but many physicians , especially in developing countries , continue to prescribe antibiotic treatment because they believe it prevents progression to more severe ARI . To find out whether ampicillin treatment conferred any benefit over supportive care alone , a r and omised , controlled trial was carried out among 889 children ( under 5 years ) with mild ARI in Indonesia . 447 were r and omly allocated ampicillin ( 25 - 30 mg/kg body weight three times daily for 5 days ) plus supportive care ( continued breastfeeding , clearing of the nose , and paracetamol to control fever ) ; 442 were allocated supportive care only . The treatment groups were almost identical after r and omisation in terms of age , sex , level of parental education , history of measles immunisation , and fever . After 1 week the percentages cured were nearly identical ( 204 [ 46 % ] ampicillin ; 209 [ 47 % ] control ) , as were the percentages of cases progressing to moderate ARI ( 56 [ 13 % ] vs 53 [ 12 % ] ) . The effect of treatment was not modified by age , sex , measles immunisation status , or the educational level of the parents . At the 2-week follow-up , the percentages cured were 62 % ( 277 ) in the ampicillin group and 58 % ( 256 ) in the control group ; 14 % of both groups had progressed to moderate Output:	There is no evidence of benefit from antibiotics for the common cold or for persisting acute purulent rhinitis in children or adults . There is evidence that antibiotics cause significant adverse effects in adults when given for the common cold and in all ages when given for acute purulent rhinitis .
MS22508	*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 comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results Background : A phase-III trial that included fifty-three patients undergoing unilateral primary total knee arthroplasty with cement was conducted to investigate the hemostatic efficacy of fibrin sealant . Methods : Following cementing of the joint , 10 mL of fibrin sealant was sprayed onto the wound before tourniquet deflation and wound closure . No placebo was used in the control group . All patients received drains . Results : Within twelve hours after the surgery , the amount of bloody drainage was 184.5 ± 28.9 mL ( mean and st and ard error ) in the fibrin-sealant group ( information available for twenty-three patients ) and 408.3 ± 54.6 mL in the control group ( information available for twenty-three patients ) ( p = 0.002 , after adjustment for variance in the time that the drainage was measured ) . On the first postoperative day , the hemoglobin level had decreased by 20.1 ± 2.1 g/L in the fibrin-sealant group ( information available for twenty-two patients ) and by 27.3 ± 2.1 g/L in the control group ( information available for twenty-four patients ) . After adjustment for baseline values , the decrease in the hemoglobin level was 28.9 % less in the fibrin-sealant group than in the control group ( p = 0.005 , 95 % confidence limits = 10.2 , 43.7 ) . There were no seroconversions in the fibrin-sealant group . Conclusion : These results suggest that fibrin sealant can safely reduce bloody drainage following total knee arthroplasty while maintaining higher hemoglobin levels 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 Closed suction drains reduce postoperative hematoma formation , but create an entry portal for bacteria and thus increase the risk of infection . This study attempts to establish when the risks of wound drainage outweigh the benefits . In a prospect i ve clinical trial , wound drains were used in all patients having a total knee or total hip arthroplasty . Timing of drain removal and amount drained were recorded . Drain-site swabs were sent with drain tips for bacteriology . Results suggest that the likelihood of bacterial colonization increases while wound drainage decreases with time . The authors conclude that the optimal time to remove drains is 24 hours after total joint arthroplasty Sixty patients undergoing total knee replacement were r and omized to receive either a cold compression dressing ( Cryo/Cuff , Aircast , UK ) or a modified Robert Jones b and age immediately after surgery . The cold compression dressing was used for a minimum of 6 h per day throughout the hospital stay , and the modified Robert Jones b and age remained in place for 48 h from the time of operation . The 2 groups of patients were compared during their hospital stay for blood loss , range of movement , pain scores and need for analgesia . No difference was found between the 2 groups except for less blood loss in the surgical drains in the cold compression group ( P<0.05 ) . Postoperative complications were seen in both groups , but no complication was associated with either the cold compression dressing or the modified Robert Jones b and age . RésuméEtude r and omisée de 60 patients qui , immédiatement après une arthroplastie totale du genou ont eu soit un pansement compressif froid de type “ Cryocuff ” soit un pansement compressif de type Robert Jones . Le pansement froid a été utilisé 6 heures par jour pendant la durée de l'hospitalisation t and is que le pansement compressif de type Robert Jones a été laisse en place pendant 48 heures après l'opération . Aucune différence statistiquement significative n'a pu être mise en évidence entre les deux groupes , à l'exception des pertes sanguines dans le drainage , moins importantes dans le premier groupe de patients . Nous avons eu des complications post opératoires dans les deux groupes mais aucune corrélation n'a pu être établie entre ces complications et le type de b and age appliqué 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 Background : The purpose of this study was to determine whether repeated clamping of a suction drainage system will result in less external blood loss , blood transfusion and no increase in complications compared to a routine continuous suction drainage system . This was a r and omized prospect i ve study on patients undergoing total knee arthroplasty Introduction To study the clinical outcome of two methods of drain clamping after total knee arthroplasty and to determine the effect on blood loss and blood transfusion . Patients and methods A prospect i ve study involving 73 patients , r and omized into two groups . Group 1 included patients in whom the drain was clamped for 1 h postoperatively , after which it was released and kept open for 48 h. Group 2 included patients in whom the drain was clamped and released for 10 min every 2 h for 24 h. The drain was removed at 48 h in both groups . Patient ’s demographic details , intraoperative and postoperative blood loss , and haemoglobin values on the preoperative and postoperative days ( 1 , 4 , 7 , 14 ) were recorded . Results The mean postoperative drainage in group 1 was 520.65±170 ml , which was significantly higher than that of group 2 , 367.62±141.1 ml ( p<0.05 , Student ’s t-test ) . The drain charting shows 65 % of drainage volume occurs in the first 8 h in both groups . The study suggests a reduction in the incidence of blood transfusion in the 2-hourly groups , although it was not statistically significant . There was a difference in the haemoglobin drop between both groups , but statistically the p value was marginally above 0.05 ( p=0.086 ) and hence not significant . Conclusion The method of 2-hourly clamping of drain and release for 10 min significantly reduces postoperative blood loss , without any added increase of complication , after total knee arthroplasty Total knee arthroplasty is sometimes associated with major post-operative bleeding , often requiring transfusion . A prospect i ve , r and omised study was undertaken to assess the effect on post-operative bleeding of delaying release of the clamp on the suction drains . One hundred patients were allocated into two groups : Group A- immediate release of drain following release of tourniquet , and Group B- delayed release of the drain clamp by one hour . There was a statistically significant reduction ( p = < 0.001 ) in postoperative bleeding between group A ( 1050 ml ; 95%CI 728 - 1172 ml ) compared to group B ( 732 ml ; 95 % CI 620- 845 ml ) . Average drop in corrected haemoglobin and postoperative transfusion requirement were also less in the delayed group . The results show that delaying release of the drains by one hour reduces postoperative blood loss and transfusion requirement following total knee arthroplasty In this study we describe the potential role of autologous platelet gel and fibrin sealant in unilateral total knee arthroplasty to improve the postoperative range of motion and to reduce the incidence of arthrofibrosis . Total knee arthroplasty is often associated with a considerable amount of post-operative blood loss . Persistent limited motion directly after surgery may ultimately result in arthrofibrosis . To counteract these effects we investigated whether the use of autologous derived platelet gel and fibrin sealant would reduce postoperative blood loss , decrease the impaired range of motion and the incidence of arthrofibrosis . All patients were consecutively operated and assigned to the study or control groups . Study group patients ( n = 85 ) were treated with the application of autologous platelet gel and fibrin sealant at the end of surgery . Eighty patients were operated without the use of platelet gel and fibrin sealant , and served as the control group . The postoperative hemoglobin decrease , range of motion and length of hospitalization were recorded . During a 5-month postoperative period patients were followed to observe the incidence of arthrofibrosis . In patients in the treatment group the hemoglobin concentration in blood decreased significantly less when compared to the control group . They also showed a superior postoperative range of motion when compared to those of the control group ( P < 0.001 ) . The incidence of arthrofibrosis and subsequent forced manipulation was significantly less ( P < 0.001 ) in patients managed with platelet gel and fibrin sealant . We conclude that peri-operatively applied platelet gel and fibrin sealant may improve the range of motion after total knee arthroplasty , decreases the length of stay and may reduce the incidence of arthrofibrosis We attempted to decrease the amount of postoperative bleeding after total knee arthroplasty ( TKA ) by clamping the suction drain and through retro grade infusion of saline containing a low concentration of epinephrine . When TKA was completed and the sutured wound was b and aged , 50 ml of saline containing epinephrine diluted to 1:200,000 and 0.5 g of antibiotic was injected into the knee joint via the inserted suction drain . The drain was clamped for 20 hours and then unclamped to begin aspiration until 48 hours after surgery . To clarify the effectiveness of this method , patients were divided into three groups . Group I consisted of 116 knees ( in 95 patients ) infused with 50 ml saline containing a low dose of epinephrine : Group II was composed of 70 knees ( 42 patients ) infused with 50 ml saline only ; and Group III included 97 knees ( 78 patients ) who did not undergo this drain-clamp method . The average amount of postoperative bleeding was 207 ml in Group I , 255 ml in Group II ( p < 0.01 ) , and 501 ml in Group III ( p < 0.001 ) . With this method of using saline with a low dose of epinephrine and sustained clamping of up to 20 hours , we have been able to operate on elderly patients with rheumatoid arthritis without blood transfusion , even in cases of simultaneous bilateral TKA . Drain-clamping with saline infusion effectively controlled postoperative bleeding after TKA , and when epinephrine was added to the saline , the hemostatic effect was even greater than that of saline alone A prospect i ve study was conducted to determine the optimal clamping time in the drain-clamping method after total knee arthroplasty . In a r and omized trial , 44 primary total knee arthroplasties were studied after the drain-clamping method using diluted epinephrine solution was applied for 1 hour or 24 hours . The mean blood loss into the drains was less in the 24-hour group compared with the 1-hour group ( 35 mL in the 24-hour group and 247 mL in the 1-hour group ) . No statistically significant difference was found in hemoglobin or hematocrit levels between the 2 groups after surgery . Only 1 patient ( 4.5 % ) in the 1-hour group and 2 Output:	The results demonstrated that drainage clamping could decrease the volume of drainage , but only clamping for no less than 4 hours could reduce the true blood loss . There was no significant difference between the 2 groups regarding blood transfusion , postoperative range of motion , incidence of thromboembolic events , and wound complications . The current evidence can not confirm the advantage of clamping drainage after TKA
MS22509	*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 purpose of the present study was to investigate whether different walking patterns in healthy subjects and in coper and non-coper subjects with deficient anterior cruciate ligaments could be quantified . An inverse dynamics approach was used to calculate joint kinematics and kinetics for flexion and extension . EMG signals of the hamstrings and quadriceps muscles were recorded . The results showed that the peak knee flexion angle was greater in the copers than in the controls . There was a positive correlation between the peak knee extensor moment and peak knee flexion angle . Furthermore , at a given peak knee flexion angle , the peak knee extensor moment was significantly larger in the controls than in the non-copers . The hip extensor moment in the copers was significantly larger than that of the non-copers and the controls . In conclusion , the three groups walked according to different patterns . It is suggested that the copers stabilized their knee joint by co-contraction of the hamstrings and quadriceps muscles , while the non-copers lacked this ability . Instead , the non-copers reduced the knee extensor moment in order to decrease anterior displacement of the tibia . The walking pattern differences observed between the copers and non-copers may explain their different post-injury activity levels Stair ascent and descent requires large knee motions and muscle forces that can be challenging for people with anterior cruciate ligament ( ACL ) deficiency . Movement and muscle activity patterns were compared in two groups of ACL deficient subjects and a group of uninjured subjects . The ACL deficient subjects were prospect ively classified according to functional ability . " Copers " were defined as individuals with complete ACL rupture and no symptoms of knee instability and participated in high-level sports without difficulty . " Non-copers " were defined as ACL deficient individuals who had instability with low-level daily activities and were not able to participate in sports . Sagittal plane kinematic and kinetic data from the hip , knee and ankle and electromyographic data from the vastus lateralis , lateral hamstring , medial gastrocnemius , and soleus were collected as subjects stepped up and over a 26 cm high step . Both coper and non-coper subjects had altered movement patterns as they controlled the rapid movement from step ascent to descent with their involved limbs . Only non-copers used significantly different movement patterns on their involved limb compared to controls after they had descended from the step and their involved side accepted the weight of the body . Classifying subjects by functional ability result ed in more pronounced differences in movement patterns between non-copers and copers . Copers moved more like uninjured subjects Abstract The aim of this study is to analyse the changes in select gait parameters following anterior cruciate ligament ( ACL ) reconstruction . The study was performed on 15 subjects who underwent ACL reconstruction by the bone-patellar tendon-bone technique . Gait analysis was performed using the Elite three-dimensional ( 3D ) optoelectronic system ( BTS ) , a Kistler force platform and the Telemg telemetric electromyograph ( BTS ) . Kinematic data were recorded for the principal lower limb joints ( hip , knee and ankle ) . The examined muscles include vastus lateralis , rectus femoris , biceps femoris and semitendinosus . The results obtained from the operated subjects were compared with those of 10 untreated subjects and 5 subjects without ACL damage . In the operated subjects the knee joint angular values regained a normal flexion pattern for the injured limb during the stance phase . The analysis of joint moments shows : ( a ) sagittal plane : recovery of the knee flexion moment at loading response and during preswing ; ( b ) frontal plane : recovery of the normal patterns for both hip and knee adduction-abduction moments during the entire stance phase . The examination of ground reaction forces reveals the recovery of frontal component features . The EMG traces show the normal biphasic pattern for the operated subjects as compared to the untreated subjects . The results suggest that the gait parameters shift towards normal value patterns OBJECTIVE To establish the gait adaptations of patients with anterior cruciate ligament deficiency during stair ascent . DESIGN Joint kinematics and kinetics during stair climbing were measured in both knees of normal subjects and unilateral anterior cruciate ligament deficient patients . BACKGROUND As there is limited research pertaining to activities other than level walking , the purpose of the current study was to eluci date the gait of patients with anterior cruciate ligament deficiency during stair climbing to determine the effects of the deficiency on knee joint motion and moments as compared with normal knee function . METHODS A motion analysis system was used to measure and calculate kinematic and kinetic data for six normal subjects and nine patients with unilateral anterior cruciate ligament deficiency during stair ascent on a specially constructed staircase . Left and right leg data were analysed to reveal between-limb differences for each subject . RESULTS Patients with anterior cruciate ligament deficiency displayed a significant ( P < 0.05 ) reduction of up to 50 % in peak knee flexion moments in their involved knee . In the present study where a step height of 15.5 cm was used , peak flexion moments in all subjects ' limbs occurred at knee flexion angles of about 40 degrees during single limb support . CONCLUSION The current study showed that most patients with an anterior cruciate deficient knee adapted their gait during stair ascent . RELEVANCE As stair climbing is a common activity , its effect on gait is relevant to better underst and appropriate treatment and management strategies of patients with anterior cruciate ligament deficient knees The objective of this study is to determine how kinematical parameters and electromyography data of selected muscles may change as a result of anterior cruciate ligament ( ACL ) deficiency and following ACL reconstruction . The study was conducted on 25 anterior cruciate ligament deficient subjects prior to and 6 weeks , 4 months , 8 months and 12 months following ACL reconstructive surgery using the bone-patellar tendon-bone technique . Gait analysis was performed by applying the zebris three-dimensional ultrasound-based system with surface electromyograph ( zebris ) . Kinematic data were recorded for the lower limb . The muscles surveyed include vastus lateralis and medialis , biceps femoris and adductor longus . The results obtained from the injured subjects were compared with those of 51 individuals without any ACL damage whatsoever . Acute ACL deficient patients exhibited a quadriceps avoidance pattern prior to and 6 weeks following surgery . No quadriceps avoidance phenomenon develops in chronic ACL deficient patients . In operated individuals , tempo-spatial parameters and the knee angle regained a normal pattern for the ACL-deficient limb during gait as early as 4 months following surgery . However , the relative ACL movement parameter , which describes the tibial translation into the direction of ACL , and the EMG traces show no significant statistical difference compared with the same values of the healthy control group just 8 months following surgery . The analysis of spatial-temporal parameters and EMG traces show that the development of a quadriceps avoidance pattern is less common than previously reported . These data suggest that anterior cruciate ligament deficiency and reconstruction produce considerable changes in the lower extremity gait pattern . The results suggest that gait parameters tend to shift towards a normal value pattern ; and the re-establishment of pre-injury gait patterns-including the normal biphase of muscles-takes at least 8 months to occur Output:	INTERPRETATION Effect sizes comparing knee joint moments in injured vs. healthy control subjects appear to be slightly higher while jogging than walking , and higher in ACL-deficient patients compared to reconstructions . Consequently , it is difficult to make inferences with confidence during these tasks
MS22510	*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: 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 Study design : Retrospective analysis . Objectives : To evaluate the efficacy of intrathecal baclofen ( ITB ) for upper extremity spastic hypertonia in tetraplegia of spinal origin . Setting : University of Alabama at Birmingham hospital . Methods : The medical records of 14 individuals with tetraplegia of spinal origin who underwent intrathecal baclofen pump placement were review ed . The effects of intrathecal baclofen on spasm frequency , deep tendon reflexes , and tone ( Ashworth scale ) were assessed for the upper and lower extremities for a 1-year follow-up period . Results : There were statistically significant declines in upper extremity spasm scores ( 1.8 points , P=0.012 ) , reflex scores ( 1.4 points , P<0.0001 ) and Ashworth scores ( 0.6 points , P<0.0001 ) for the 1-year follow-up period . For the lower extremities , all decreases were significant ( P<0.0001 ) . There was also a statistically significant ( P<0.0001 ) increase in intrathecal baclofen dosage requirements during the 1-year follow-up period to maintain the reductions in spasm frequency , reflexes and tone . Conclusions : Intrathecal baclofen is a safe and effective intervention for treating upper extremity hypertonia of spinal origin . In addition , the level of intrathecal catheter placement is felt to be of importance .Spinal Cord ( 2001 ) 39 , 413–419 The effects of intrathecal baclofen infusion were studied in 9 spinal cord injury patients whose spasticity had been refractory to oral medications . In a two stage , placebo controlled trial , baclofen was administered into the lumbar intrathecal space and subsequent clinical and neurophysiologic changes were assessed . In stage 1 , 9 patients underwent a 5 day percutaneous infusion of baclofen and placebo via an external pump . Ashworth and reflex scores were assessed at time of enrollment , after infusion of that amount of baclofen which provided optimal spasticity control and after intrathecal infusion of placebo . The mean Ashworth grade decreased from 3.78 ± 1.34 to 1.16 ± 0.48 ( p < 0.001 ) while mean reflex score decreased from 3.57 ± 1.05 to 0.64 ± 0.87 ( p < 0.001 ) . These values differed significantly from those associated with placebo therapy ( Ashworth grade —2.54 ± 1.04 , p < 0.001 ; reflex score—2.56 ± 1.04 , p < 0.01 ) . Objective improvements in functional abilities and independence were noted in 8 patients , while somatosensory and brainstem auditory evoked potentials were unchanged in all patients . Urodynamic evaluation revealed increased bladder capacity in 3 patients , while in 4 no change was observed . In Stage 2 , permanent programmable infusion pumps were implanted in 7 patients who demonstrated a good response during Stage 1 . In this group , mean Ashworth score decreased from 3.79 ± 0.69 to 2 ± 0.96 ( p < 0.001 ) and mean reflex score decreased from 3.85 ± 0.62 to 2.18 ± 0.43 ( p < 0.001 ) . Baclofen dosage increased from 182 ± 135 to 528 ± 266 mcg/day over the 3 - 22 month follow-up period . Most of the dosage increase occurred within the initial 12 months following infusion pump implantation and tended to plateau thereafter . Minor complications such as catheter dislodgement/kinking and nausea occurred infrequently while no device related infections were observed . There was no clinical evidence of any significant baclofen neurotoxicity either in Stage 1 or 2 . The only ambulatory patient developed marked lower extremity weakness during Stage 1 intrathecal baclofen infusion and was temporarily unable to walk . We conclude that continuous administration of intrathecal baclofen is an effective and safe modality for spasticity control in patients who are refractory to oral medications A total of 93 patients with intractable spasticity due to either spinal cord injury ( 59 cases ) , multiple sclerosis ( 31 cases ) , or other spinal pathology ( three cases ) were entered into a r and omized double-blind placebo-controlled screening protocol of intrathecal baclofen test injections . Of the 88 patients who responded to an intrathecal bolus of 50 , 75 , or 100 micrograms of baclofen , 75 underwent implantation of a programmable pump system for chronic therapy . Patients were followed for 5 to 41 months after surgery ( mean 19 months ) . No deaths or new permanent neurological deficits occurred as a result of surgery or chronic intrathecal baclofen administration . Rigidity was reduced from a mean preoperative Ashworth scale score of 3.9 to a mean postoperative score of 1.7 . Muscle spasms were reduced from a mean preoperative score of 3.1 ( on a four-point scale ) to a mean postoperative score of 1.0 . Although the dose of intrathecal baclofen required to control spasticity increased with time , drug tolerance was not a limiting factor in this study . Only one patient withdrew from the study because of a late surgical complication ( pump pocket infection ) . Another patient received an intrathecal baclofen overdose because of a human error in programming the pump . The results of this study indicate that intrathecal baclofen infusion can be safe and effective for the long-term treatment of intractable spasticity in patients with spinal cord injury or multiple sclerosis OBJECTIVES To assess long-term efficacy and functional benefits of intrathecal baclofen for severe spinal spasticity . DESIGN A prospect i ve before-after trial . SETTING A neurological rehabilitation department of a university hospital . Pump implantation was realized in neurosurgery ; follow-up was carried out mostly on an outpatient basis . PATIENTS Eighteen patients with severe and disabling spinal spasticity received intrathecal baclofen by an implantable pump ; average follow-up was 37.4 months ( range , 9 to 72 ) . MAIN OUTCOME MEASURES Spasticity ( Ashworth and spasms frequency scores ) ; disability ( Functional Independence Measure [ FIM ] ) . RESULTS A significant decrease in tone and spasms was observed in all patients . Tolerance appeared during the first 6 to 9 months . Later on , efficacy remained stable , except in cases of mechanical problems of the pump or catheter . Functional assessment found a highly significant ( p < .001 ) increase of FIM score ( particularly for bathing , dressing lower body , transfers , and in some cases , locomotion ) . This was particularly marked in patients with thoracic spinal cord lesion . In cases of severe upper limb dysfunction , FIM was only improved for wheelchair displacements , due to a better sitting position , but nursing became easier and life comfort was enhanced . Severe side effects ( overdose ) were observed in two cases . CONCLUSION Efficacy remained stable after 6 to 9 months . Marked improvement of functional independence was observed in paraplegic patients . Improvement was less spectacular in patients with severe upper limb dysfunction , but nevertheless appreciable in terms of life comfort and use of attendants A prospect i ve trial to demonstrate the efficacy of intrathecal baclofen therapy by implanted pump for adults with spasticity due to spinal cord injury or multiple sclerosis was initiated in our hospital . Of the 140 patients assessed , 7 met the following criteria for inclusion in the study : a modified Ashworth score > 3 , a spasm frequency score > 2 , and an inadequate response to oral anti-spasticity drugs , ( i.e. , baclofen , clonidine and cyproheptadine ) . All patients responded to intrathecal bolus injection of baclofen in the double blind , placebo-controlled screening phase ( mean bolus dose = 42.8 micrograms ) . Programmable Medtronic pumps were implanted in 4 patients while 3 patients received non-programmable Infusaid pumps . Post-implantation , a marked decrease in spasticity occurred with a significant reduction of the Ashworth score ( mean = 1.8 , p < .005 ) , a reduced spasm score ( mean = 0.8 , p < .005 ) , and an improved leg swing in the pendulum test . These effects were maintained during a follow-up of 24 - 41 months ( average infusion dose = 218.7 micrograms/day ) . The gross cost-savings due to reduced hospitalizations related to spasticity was calculated by comparing the cost for the two year period before pump implantation to the same period after treatment for 6 of the 7 patients . The cost of in-hospital implantation as well as the cost of the pumps were deducted from the gross savings . There was a net cost-saving of $ 153,120 . Our findings agree with the reported efficacy and safety of intrathecal baclofen treatment , and illustrate the cost-effectiveness of this treatment 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 This study assessed the safety and efficacy of intrathecal baclofen in the treatment of intractable spasticity caused by spinal cord injury or multiple sclerosis . Twenty-three patients with severe chronic spasticity underwent bolus test dosing with 50 , 75 , or 100 micrograms of intrathecal baclofen administered by lumbar puncture . All patients were either refractory to oral baclofen at a dose of 120 mg/d or side effects were unacceptable at a lower dose . There was a significant decrease in tone and spasticity in all 23 patients . Nineteen patients underwent implantation of a programmable pump and intrathecal catheter design ed to deliver baclofen directly to the spinal cord . Rigidity ( tone ) was decreased from a mean prebolus Ashworth score of 3.8 to a mean postbolus Ashworth score of 1.5 and spasms from a mean prebolus score of 3.5 to a mean postbolus score of 1.2 for a minimum of 4 hours . Patients have been observed for a mean of 16 months ( range 2 to 34 months ) . Ashworth scores have remained reduced to an acceptable level ( < or = Output:	There was substantial level 4 evidence that intrathecal baclofen is effective in reducing spasticity .
MS22511	*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 study aims to evaluate the efficacy of methadone as substitute for morphine and to investigate if the addition of acetaminophen could reduce the time to attain an equianalgesic dose of methadone and /or to improve the level of pain control in oncologic patients . Patients and methods Fifty patients on stable doses of morphine for 1 week were switched to methadone using a “ stop – start ” strategy and r and omized in a double-blind fashion to receive either acetaminophen ( 750 mg PO every 6 hours ) or placebo for a 7-day period . We collected data regarding level of pain , side effects , and quality of life . Results Substitution of morphine for methadone result ed in a significant reduction in constipation ( p < 0.001 ) and xerostomia ( p = 0.03 ) . There was also an improvement in the numeric pain scale ( p = 0.03 ) as well as a significant improvement in the functional level and symptomatology according to the QLQ-C30 question naire . Addition of acetaminophen did not improve pain control or reduce the time of stabilization of analgesia once methadone was introduced . At the end of the study , most patients ( 70.8 % , p = 0.001 ) preferred methadone to morphine . Conclusions Early switching from morphine to methadone was a safe and efficient strategy for the reduction of side effects and improvement of analgesia , allowing for a comfortable dosing regimen . In this scenario , the association with acetaminophen did not improve pain control or reduce the time to achieve an equianalgesic dose of methadone The role of non-steroidal anti-inflammatory drugs ( NSAIDs ) in cancer pain has been well established in the treatment of mild pain and in association with opioids in the treatment of moderate to severe pain . The aim of this study was to verify the effects of NSAIDs on morphine escalation in advanced cancer patients with pain followed-up at home and to assess the pharmacoeconomic implication s. A prospect i ve r and omised controlled study was carried out in 156 consecutive advanced cancer patients with pain followed-up at home in the period December 1999-December 2000 . In this group of patients , 47 were selected with pain progression after 1 week of opioid stabilisation . Patients were r and omly assigned to one of two groups : group ' O ' patients were treated with continuing opioid escalation according to their clinical needs ; group ' OK ' received ketorolac 60 mg/daily orally ( p.o . ) in three doses and then continued opioid escalation according to their clinical situation . Performance status , doses of morphine before and after starting treatment , mean weekly pain intensity ( assessed by means of a numerical scale from 0 to 10 ) , mean weekly symptoms intensity , adverse effects and pain mechanisms were recorded . Moreover , drug costs per day in both groups were calculated . Patients who received ketorolac in addition to morphine showed a better analgesia after a week in comparison to the group treated with morphine only ( P=0.005 ) . Thereafter , morphine escalation was slower and the maximum morphine dose was lower in the group treated with ketorolac . The incidence and the severity of gastric discomfort was more evident in patients treated with ketorolac , while constipation was significantly increased in patients who received morphine only . Drug costs per day were similar in both groups ; statistical differences were observed in patients who started on lower morphine doses ( < 100 mg/daily ) in the two groups ( 4.3 in the ketorolac-morphine group versus 3.4 in the morphine group ; P=0.012 ) . The use of NSAIDs reduces the need for an opioid dose escalation or allows the use of lower doses . Their use is associated with a more intense gastric discomfort , but results in less opioid-related constipation . The eventual additive cost for NSAIDs therapy is negligible , especially in patients taking high doses of morphine Introduction Adjunct nonopioid analgesics may improve pain control in patients with cancer needing morphine or its derivates . Dypirone is a cheap nonopioid analgesic widely used in many countries . Objective The objective of the study was to evaluate , whenever morphine was started , if associating dipyrone with it would improve pain control and if this effect was time dependent . Material s and methods This is a double-blind placebo-controlled r and omized crossover study . Thirty-four ambulatory cancer patients experiencing cancer-related pain for which oral morphine was to be started at the dose of 10 mg orally ( PO ) every 4 h were r and omized to take either dipyrone 500 mg PO every 6 h or placebo . After 48 h , patients would be switched from dipyrone to placebo and vice versa . Pain was the primary outcome and was measured using a visual analogue scale before starting medications , at 48 and 96 h. Results We r and omized 16 patients to start with placebo ( group 1 ) and 18 with dipyrone ( group 2 ) . Pain scores for groups 1 and 2 were at baseline : 7.31 ± 0.29 vs 6.88 ± 0.28 ( p = 0.3 ) , at 48 h : 7.06 ± 0.32 vs 5.5 ± 0.31 ( p = 0.001 ) , and at 96 h : 3.18 ± 0.39 vs 1.94 ± 0.37 ( p = 0.03 ) . Both groups had significant improvements in pain scores after introducing dipyrone ( p < 0.001 , for both ) . Main toxicities were nausea , vomiting , epigastric pain , and myalgias . Twenty-eight patients chose dipyrone , four placebo , and two were indifferent . Conclusions We conclude that dipyrone adds significantly to the analgesic effect of morphine and , when given at the time of starting morphine , results in better pain scores even after dipyrone is discontinued & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies Cobrotoxin produces intense analgesia but it has an onset of response of 1 - 3 h which hampers its clinical use in cancer pain . Recently , a compound analgesic formulation combining cobrotoxin , tramadol hydrochloride and ibuprofen ( Compound Keluoqu , CKLQ ) has become available in China . The aim of this study was to evaluate the clinical efficacy of CKLQ for moderate to severe cancer pain . A consecutive series of patients with chronic moderate to severe cancer pain was enrolled into two multicenter trials . Of the 230 eligible patients , 119 were assigned to a r and omized , double-blind , cross-over study , while 111 entered an open-label study . They were all of Han-China nationality and had a mean age of 52.0 and 55.4 years and a mean body weight of 55.6 and 52.9 kg , respectively . A total of 11 patients discontinued the study , 6 ( 54.5 % ) because of insufficient pain relief and 5 due to the occurrence of adverse events . In the cross-over study , 59 patients were r and omized to receive a CKLQ package with 2 CKLQ tablets ( each containing 0.16 mg cobrotoxin , 25 mg tramadol hydrochloride and 50 mg ibuprofen ) and 2 placebo capsules , a placebo package with 2 placebo tablets and 2 placebo capsules , and an active control package with 2 tramadol hydrochloride capsules ( each containing 50 mg tramadol hydrochloride ) and 2 placebo tablets ( arm A ) , and 60 to receive a tramadol hydrochloride package , a placebo package and a CKLQ package ( arm B ) , sequentially and only once . Patients in the open-label study only received CKLQ and were given the option to continue for up to 7 days as long as they had satisfactory pain relief . Pain response was classified as CR , PR and NC . CR was defined as 100 % pain relief , with a pain score of 0 on a 0 - 10 VAS . PR was defined as decreased to mild pain , with a pain score of no more than 4 on a 0 - 10 VAS . NC was defined as pain that either remained unchanged or that was reduced from severe to moderate at baseline , with a VAS pain score of more than 4 after treatment . One hundred and eight patients completed the cross-over study with all the three drug units . The overall rate of pain relief was 93/111 ( 83.7 % ) for CKLQ , 75/110 ( 68.2 % ) for tramadol hydrochloride ( P=0.011 ) and 39/111 ( 35.1 % ) for placebo ( P<0.001 ) . The mean duration of pain relief with CKLQ was significantly longer than that of the other two agents ( P<0.001 ) . Of the 35 patients who did not respond to tramadol hydrochloride , 27 ( 77.1 % ) responded to CKLQ , while of the 18 who did not respond to CKLQ , 8 ( 55.6 % ) achieved satisfactory pain control with tramadol hydrochloride . In the open-label study , the overall relief rate of a single-dose of CKLQ was 99/111 ( 89.2 % ) . A reduction in the percentage of complete relief , an increase in that of PR and a significant decrease in duration of relief were observed after continuous treatment with at least 10 doses of CKLQ . The frequency of adverse events for CKLQ was similar to that of tramadol hydrochloride . The results of the r and omized , double-blind , cross-over study and the open-label study of CKLQ in cancer patients with chronic moderate to severe cancer pain suggest that the CKLQ may be valuable for the treatment of chronic moderate to severe cancer pain . However , the tolerance of CKLQ remains to be further defined Objetives The purpose of this study was to compare the analgesic efficacy and tolerability of opioids hydrocodone and tramadol in the relief of cancer pain . Methods One hundred and eighteen patients with chronic cancer pain participated in a double-blind , r and omized controlled trial . Sixty-two patients received hydrocodone and 56 patients received tramadol . Results Hydrocodone/acetaminophen was effective in relieving pain in 56.5 % of the patients at the starting dose of 25 mg/2500 mg/d . An additional 14.5 % of the patients responded to a double dose , and the remaining 29 % of patients did not experience any pain relief from hydrocodone administration . One dose of tramadol at 200 mg/d produced pain relief in 62 % of the patients and alleviated pain in another 11 % of patients at a dose of 400 mg/d , and remaining 27 % of patients did not experience pain relief from tramadol . No significant statistical difference in the analgesic efficacy of tramadol clorhydrate and hydrocodone/acetaminophen was found . The groups differed significantly in the incidence of side effects like nausea ( P=0.03 ; relative risk ( RR ) , 1.69 ; confidence interval ( IC ) 95 % , 1.03 - 2.77 ) , vomiting ( P=0.02 ; RR , 2.21 ; IC 95 % , 1.14 - 4.32 ) , dizziness ( P=0.03 ; RR , 2.12 ; IC 95 % , 1.17 - 3.86 ) , loss of appetite ( P=0.02 ; RR , 3.27 ; IC 95 % , 1. Output:	There is no proof that they should be used to start the treatment and how long they should be administered when opioid treatment is added on top . While paracetamol seems to be devoid of any benefit , particularly if given at usual clinical doses which should be less than 4 g/day , ketorolac seems to provide an additive analgesic effect even in patients receiving different doses of opioids . The main indication from the analysis of these data is that NSAIDs could be given in patients receiving opioids , evaluating their benefit and weight on opioid therapy in individual patients who have a favorable response to justify a prolonged use
MS22512	*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: While an admission to the Intensive Care Unit ( ICU ) is stressful , the impending transfer from ICU to the ward can also result in anxiety for patients and their families . The aim of this study was to identify the effect of an ICU liaison nurse on anxiety experienced by patients and their families just prior to transfer to the ward . This block intervention study used a repeated before and after design , with the first control and intervention periods of 4 months , a wash-out period of 1 month , and then a second control and intervention period of 4 months duration . That is , after 4 months of control and another 4 months of intervention , the liaison nurse services were withdrawn and no data collection occurred for a month ( wash-out ) then a second set of 4-month blocks of control and intervention were undertaken . A st and ard transfer protocol was followed during the control periods whereas during the intervention periods , the liaison nurse prepared patients and their families for transfer to the ward . The State Trait Anxiety Form Y ( State ) was used to measure anxiety just prior to physical relocation to the ward . A total of 115 patients ( 62 control , 53 intervention ) and 100 families ( 52 control , 48 intervention ) were enrolled in the study . There was no difference in anxiety scores between the control and intervention groups in either patients or family groups . This study did not demonstrate a statistically significant beneficial effect of the liaison nurse in terms of pre-transfer anxiety , however it highlights several method ological issues that must be considered for future research including sample size estimates , timing and measurement of transfer anxiety and finally the intervention itself Background Family members of patients in intensive care units ( ICUs ) are at risk for mental health morbidity both during and after a patient ’s ICU stay . Objectives To determine prevalences of and factors associated with anxiety , depression , posttraumatic stress and complicated grief in family members of ICU patients . Design Prospect i ve , longitudinal cohort study . Participants Fifty family members of patients in ICUs at a large university hospital participated . Measurements We used the Control Preferences Scale to determine participants ’ role preferences for surrogate decision-making . We used the Hospital Anxiety and Depression Scale , Impact of Event Scale , and Inventory of Complicated Grief to measure anxiety and depression ( at enrollment , 1 month , 6 months ) , posttraumatic stress ( 6 months ) , and complicated grief ( 6 months ) . Results We interviewed all 50 participants at enrollment , 39 ( 78 % ) at 1 month , and 34 ( 68 % ) at 6 months . At the three time points , anxiety was present in 42 % ( 95 % CI , 29–56 % ) , 21 % ( 95 % CI , 10–35 % ) , and 15 % ( 95 % CI , 6–29 % ) of participants . Depression was present in 16 % ( 95 % CI , 8–28 % ) , 8 % ( 95 % CI , 2–19 % ) , and 6 % ( 95 % CI , 1–18 % ) . At 6 months , 35 % ( 95 % CI , 21–52 % ) of participants had posttraumatic stress . Of the 38 % who were bereaved , 46 % ( 95 % CI , 22–71 % ) had complicated grief . Posttraumatic stress was not more common in bereaved than nonbereaved participants , and neither posttraumatic stress nor complicated grief was associated with decision-making role preference or with anxiety or depression during the patient ’s ICU stay . Conclusions Symptoms of anxiety and depression diminished over time , but both bereaved and nonbereaved participants had high rates of posttraumatic stress and complicated grief . Family members should be assessed for posttraumatic stress and complicated grief Objective Anxiety and depression may have a major impact on a person ’s ability to make decisions . Characterization of symptoms that reflect anxiety and depression in family members visiting intensive care patients should be of major relevance to the ethics of involving family members in decision-making , particularly about end-of-life issues . Design Prospect i ve multicenter study . Setting Forty-three French intensive care units ( 37 adult and six pediatric ) ; each unit included 15 patients admitted for longer than 2 days . Patients Six hundred thirty-seven patients and 920 family members . Interventions Intensive care unit characteristics and data on the patient and family members were collected . Family members completed the Hospital Anxiety and Depression Scale to allow evaluation of the prevalence and potential factors associated with symptoms of anxiety and depression . Measurements and Main Results Of 920 Hospital Anxiety and Depression Scale question naires that were completed by family members , all items were completed in 836 question naires , which formed the basis for this study . The prevalence of symptoms of anxiety and depression in family members was 69.1 % and 35.4 % , respectively . Symptoms of anxiety or depression were present in 72.7 % of family members and 84 % of spouses . Factors associated with symptoms of anxiety in a multivariate model included patient-related factors ( absence of chronic disease ) , family-related factors ( spouse , female gender , desire for professional psychological help , help being received by general practitioner ) , and caregiver-related factors ( absence of regular physician and nurse meetings , absence of a room used only for meetings with family members ) . The multivariate model also identified three groups of factors associated with symptoms of depression : patient-related ( age ) , family-related ( spouse , female gender , not of French descent ) , and caregiver-related ( no waiting room , perceived contradictions in the information provided by caregivers ) . Conclusions More than two-thirds of family members visiting patients in the intensive care unit suffer from symptoms of anxiety or depression . Involvement of anxious or depressed family members in end-of-life decisions should be carefully discussed INTRODUCTION This intervention study examines anxiety and uncertainty in illness in families transferring from intensive care to a general ward . METHODS The pre-test , post-test design purposively allocated family members to a control ( n = 80 ) and intervention group ( n = 82 ) . The intervention group experienced a structured individualised transfer method whereas the control group received existing ad hoc transfer methods . Families were surveyed before and after transfer . RESULTS Families ' uncertainty was significantly related to their state anxiety ( P < 0.000 ) , the relationship to the patient ( P = 0.022 ) , and the unexpected nature of patients ' admission ( P < 0.000 ) . Anxiety increased significantly with reduced social support ( P = 0.002 ) . Following transfer , anxiety reduced significantly for both groups whereas uncertainty reduced significantly for the intervention group ( P = 0.03 ) . CONCLUSION Families at the time of transfer experience uncertainty and anxiety , which are significantly related in this study . The intervention significantly reduced uncertainty scores . When the family member was a parent , when admissions were unexpected , and those with fewer social supports represent potential ' at risk ' groups whose adaptation to transfer may limit their coping ability . The structured individualised method of transfer is recommended with further research of ICU families to further examine the dimension of uncertainty and how it affects patient outcomes Output:	The results of this meta- analysis show that training will decline the anxiety level of a family with patients hospitalized in the intensive care unit , although the impact is not considerable
MS22513	*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 Experimental evidence suggests that neutrophils and their metabolites play an important role in the pathogenesis of pyelonephritis . The aim of this study was to investigate the diagnostic value of polymorphonuclear elastase-a(1)-antitrypsin complex ( E-a(1)-Pi ) for the detection of acute pyelonephritis in children . METHODS Eighty-three patients , 29 boys and 54 girls , 25 days to 14 years of age , with first-time symptomatic urinary tract infection were prospect ively studied . Fifty-seven healthy children served as controls . Dimercaptosuccinic acid ( DMSA ) scan and voiding cystourethrography were performed in all patients . Plasma and urinary E-a(1)-Pi , C-reactive protein ( CRP ) , erythrocyte sedimentation rate ( ESR ) , neutrophil count , urinary N-acetyl-beta-glucosaminidase ( NAG ) , N-acetyl-beta-glucosaminidase b ( NAG b ) , and creatinine levels were measured in all patients on admission and 3 days after the introduction of antibiotics . The same markers were also measured in the control subjects . RESULTS Planar DMSA scintigraphy demonstrated changes of acute pyelonephritis in 30 of 83 children ( group A ) . It was normal in the remaining 53 children ( group B ) . The sex and age distributions were not significantly different between the 2 groups , as well as between the patients and the control subjects ( group C ) . Nineteen of the 53 children with a normal DMSA had body temperature > /=38 degrees C , whereas all but 4 children with abnormal DMSA had temperature > /=38 degrees C. Therefore , the temperature was significantly different between these 2 groups . The sensitivity and specificity of fever ( > /=38 degrees C ) as an indicator of renal involvement based on isotopic findings were 86 % and 64 % , respectively . Given the significant number of the febrile children with normal DMSA scintiscans , group B was subdivided into B(1 ) with 19 febrile children ( 14 boys and 5 girls ) and B(2 ) with 34 children whose body temperature was below 38 degrees C ( 8 boys and 26 girls ) . The sex and age distribution was significantly different between groups B(1 ) and B(2 ) . The mean age of group B(1 ) was.78 years ( range : 28 days to 9 years ; median:.25 years ; st and ard deviation : 2.1 ) . All but 1 child in this group were younger than 1 year of age . In contrast , in group B(2 ) , there were only 4 infants , the remaining 30 children were older than 2.5 years ( mean age : 6 years ; median : 7 years ; st and ard deviation : 3.5 ; range : 34 days to 12 years ) . The mean duration of fever before hospital admission was 2.8 days for group A and 1.8 days for group B(1 ) . This difference was not statistically significant . Similarly , body temperature was not significantly different between these 2 groups . The distribution of plasma E-a(1)-Pi values was normal in the control subjects . The sensitivity and specificity of plasma E-a(1)-Pi , as an indicator of renal involvement , were 96 % and 50 % , respectively , taking the 95th percentile of the reference range as a cutoff value . However , considering as a cutoff value the level of 72 microg/dL ( 95th percentile of group B(2 ) ) , its sensitivity and specificity were 74 % and 86 % , respectively . Plasma E-a(1)-Pi levels were significantly elevated in group A compared with group B and in both groups , the plasma E-a(1)-Pi values were significantly higher than in the control subjects . A significant difference also was noticed between group A and each of the subgroups B(1 ) and B(2 ) and also between the subgroups themselves . Plasma E-a(1)-Pi concentrations correlated significantly with neutrophil count in groups A ( r = .3 ) , B ( r = .4 ) , and B(2 ) ( r = .46 ) , but the correlation was not significant in group B(1 . ) ESR levels showed , among the different groups , similar differences with those of E-a(1)-Pi values . Unlike E-a(1)-Pi , CRP levels were comparable between groups A and B(1 ) , which both consisted of febrile children . Neutrophil count was not significantly different between subgroups B(1 ) and B(2 ) . ( ABSTRACT TRUNCATED Background . The st and ard recommendation for treatment of young , febrile children with urinary tract infection has been hospitalization for intravenous antimicrobials . The availability of potent , oral , third-generation cephalosporins as well as interest in cost containment and avoidance of nosocomial risks prompted evaluation of the safety and efficacy of outpatient therapy . Methods . In a multicenter , r and omized clinical trial , we evaluated the efficacy of oral versus initial intravenous therapy in 306 children 1 to 24 months old with fever and urinary tract infection , in terms of short-term clinical outcomes ( sterilization of the urine and defervescence ) and long-term morbidity ( incidence of reinfection and incidence and extent of renal scarring documented at 6 months by99mTc-dimercaptosuccinic acid renal scans ) . Children received either oral cefixime for 14 days ( double dose on day 1 ) or initial intravenous cefotaxime for 3 days followed by oral cefixime for 11 days . Results . Treatment groups were comparable regarding demographic , clinical , and laboratory characteristics . Bacteremia was present in 3.4 % of children treated orally and 5.3 % of children treated intravenously . Of the short-term outcomes , 1 ) repeat urine cultures were sterile within 24 hours in all children , and 2 ) mean time to defervescence was 25 and 24 hours for children treated orally and intravenously , respectively . Of the long-term outcomes , 1 ) symptomatic reinfections occurred in 4.6 % of children treated orally and 7.2 % of children treated intravenously , 2 ) renal scarring at 6 months was noted in 9.8 % children treated orally versus 7.2 % of children treated intravenously , and 3 ) mean extent of scarring was ∼8 % in both treatment groups . Mean costs were at least twofold higher for children treated intravenously ( $ 3577 vs $ 1473 ) compared with those treated orally . Conclusions . Oral cefixime can be recommended as a safe and effective treatment for children with fever and urinary tract infection . Use of cefixime will result in substantial reductions of health care expenditures This prospect i ve study , performed in 76 children with a urinary tract infection ( UTI ) , evaluates the diagnostic value of procalcitonin ( PCT ) and proinflammatory cytokines ( IL-1β , IL-6 and TNF-α ) in children with acute pyelonephritis documented by dimercaptosuccinic acid scintigraphy ( DMSA ) . Renal parenchymal involvement was assessed by 99 m Tc-DMSA scintigraphy within 7 days of admission . The diagnosis of acute pyelonephritis was confirmed only in patients with reversible lesions on scintigraphy . According to DMSA scan results , patients were divided into two groups , lower UTI or acute pyelonephritis . In acute pyelonephritis , serum PCT level was found to be significantly higher than it is in the lower UTI ( p < 0.001 ) . Also , significantly higher serum proinflammatory cytokines ( IL-1β , IL-6 and TNF-α ) levels were detected in those with acute pyelonephritis than those with lower UTI ( p < 0.001 ) . We conclude that both serum PCT and proinflammatory cytokine levels may be used as accurate markers for diagnosis of acute pyelonephritis Four recent prospect i ve studies have suggested that procalcitonin ( PCT ) , a polypeptide produced by the macrophage-monocyte system during severe bacterial infection , might be more specific than leukocyte count or C-reactive protein ( CRP ) in predicting acute renal involvement during an episode of febrile urinary tract infection ( UTI ) [ 1 , 2 , 3 , 5 ] . The aim of our prospect i ve study was to confirm such findings OBJECTIVE Febrile urinary tract infection ( UTI ) is a common problem among children . The diagnosis and management of acute pyelonephritis is a challenge , particularly during infancy . The distinction between acute pyelonephritis and UTI without renal involvement is very important , because renal infection may cause parenchymal scarring and thus requires more aggressive investigation and follow-up monitoring . However , this distinction is not easy among children , because common clinical findings and laboratory parameters are nonspecific , especially among young children . In an attempt to differentiate acute pyelonephritis from febrile UTI without renal lesions in a group of 100 children , we measured serum levels of procalcitonin ( PCT ) , a new marker of infection . The objective of the study was to determine the accuracy of PCT measurements , compared with C-reactive protein ( CRP ) measurements , in diagnosing acute renal involvement during febrile UTI and in predicting subsequent scars , as assessed with 99mTc-dimercaptosuccinic acid ( DMSA ) scintigraphy . DESIGN Serum CRP levels , erythrocyte sedimentation rates , leukocyte counts , and PCT levels were measured for 100 children , 1 month to 13 years of age , admitted for suspected febrile UTI ( first episode ) . Renal parenchymal involvement was evaluated with DMSA scintigraphy within 5 days after admission . The DMSA study was repeated 6 months later if the initial results were abnormal . RESULTS The mean PCT level was significantly higher in acute pyelonephritis than in UTI without renal lesions ( 4.48 + /- 5.84 ng/mL vs 0.44 + /- 0.30 ng/mL ) . In these 2 groups , the mean CRP levels were 106 + /- 68.8 mg/L and 36.4 + /- 26 mg/L , mean erythrocyte sedimentation rates were 79.1 + /- 33 mm/hour and 58.5 + /- 33 mm/hour , and leukocyte counts were 18 492 + /- 6839 cells/mm3 and 16 741 + /- 5302 cells/mm3 , respectively . For the prediction of acute pyelonephritis , the sensitivity and specificity of PCT measurements were 83.3 % and 93.6 % , respectively ; CRP measurements had a sensitivity of 94.4 % but a specificity of only 31.9 % . Positive and negative predictive values for prediction of renal involvement with PCT measurements were 93.7 % and 83 % and those with CRP measurements were 61.4 % and 83.3 % , respectively . When inflammatory markers were correlated with the severity of the renal lesions , as assessed with DMSA scintigraphy , a highly significant correlation with both PCT and CRP levels was found . However , when the 2 parameters were correlated with renal scarring in follow-up scans , a significant positive association was found only for PCT levels . CONCLUSIONS Serum PCT levels may be a sensitive and specific measure for early diagnosis of acute pyelonephritis and determination of the severity of renal parenchymal involvement . Therefore , this measurement could be useful for the treatment of children with febrile UTIs , allowing prediction of patients at risk of permanent parenchymal renal lesions OBJECTIVES . The American Academy of Pediatrics recommendation for febrile infants and young children suspected of having a urinary tract infection is early antibiotic treatment , given parenterally if necessary . In support of this recommendation , data suggesting that delay in treatment of acute pyelonephritis increases the risk of kidney damage are cited . Because the risk was not well defined , we investigated renal scarring associated with delayed versus early treatment of acute pyelonephritis in children . METHODS . The research findings are derived from 2 multicenter , prospect i ve , r and omized , controlled studies , Italian Renal Infection Study 1 and 2 , whose primary outcomes dealt with initial antibiotic treatment and subsequent prophylaxis , respectively . From the 2 studies , we selected the 287 children with confirmed pyelonephritis on acute technetium-99m-dimercaptosuccinic acid scans who underwent repeat scanning to detect scarring 12 months later . The children were 1 month to < 7 years of age when they presented with their first recognized episode of acute pyelonephritis in northeast Italy . RESULTS . Progressive delay in antibiotic treatment of acute pyelonephritis from < 1 to ≥5 days after the onset of fever was not associated with any significant increase in the risk of scarring on technetium-99m-dimercaptosuccinic acid scans obtained 1 year later . The risk of scarring remained relatively constant at 30.7 ± 7 % . Clinical and laboratory indices of inflammation were comparable in all groups , as was the incidence of vesicoureteric reflux . CONCLUSIONS . Early treatment of acute pyelonephritis in infants and young children had no significant effect on the incidence of subsequent renal scarring . Furthermore , there was no significant difference in the rate of scarring after acute pyelonephritis when infants and young children were compared with Output:	The ESR test does not appear to be sufficiently accurate to be helpful in differentiating children with cystitis from children with pyelonephritis . A low CRP value ( < 20 mg/L ) appears to be somewhat useful in ruling out pyelonephritis ( decreasing the probability of pyelonephritis to < 20 % ) , but unexplained heterogeneity in the data prevents us from making recommendations at this time . Thus , at present , we do not find any compelling evidence to recommend the routine use of any of these tests in clinical practice
MS22514	*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 determine the effects of raloxifene on sexual function in postmenopausal women with pre-existing vaginal atrophy treated with vaginal estrogen cream . Methods : A total of 187 naturally postmenopausal women , 42 - 80 years of age , with signs of genitourinary atrophy were enrolled in this 6-month , multicenter , parallel-group study . Subjects were r and omized to oral raloxifene HCl 60 mg daily or matching placebo ; the same subjects were also r and omized to receive one application of either vaginal conjugated estrogen cream 0.5 g twice weekly for 6 months or non-hormonal vaginal moisturizer twice weekly for 3 months , followed by conjugated estrogen cream for 3 months . Both investigators and subjects were masked to the identity of the oral medication . The vaginal preparations were administered in an open-label fashion . The Sexual Activity Question naire ( SAQ ) was administered at baseline and at 3 and 6 months . Safety was assessed throughout the study . Results : A total of 102 women were sexually active at baseline and , of these , 82 were also sexually active at the 6-month end-point . At 6 months , raloxifene and placebo , in the presence of vaginal conjugated estrogen cream , were both associated with improvement from baseline in vaginal dryness and reduced discomfort during sexual activity . There were no significant differences between raloxifene and placebo groups in any SAQ item . Enjoyment of sexual activity significantly increased from baseline with raloxifene but not with placebo . No difference in adverse events was observed between groups . Conclusion : Raloxifene had no negative effects on sexual function in postmenopausal women with vaginal atrophy who were treated concomitantly with vaginal estrogen cream Silicone vaginal rings for the continuous release of 17 beta-oestradiol ( E2 ) with 2 constant in vitro release rates were used for the treatment of symptoms of urogenital atrophy in 2 groups of postmenopausal women . The very low dose of 7 micrograms/24 h was found to alleviate atrophic symptoms effectively and to induce significant maturation of vaginal and urethral epithelium . After a brief initial peak , the serum levels of E2 over 3 mth of treatment remained close to the detection limit . The ' undetectable ' E2 release pattern was reflected only in increased levels of oestrone sulphate . There was no evidence of a systemic metabolic response and patient acceptance of the method was excellent . Continuous low-dose release of E2 via vaginal rings consequently offers an alternative means of administering local oestrogen therapy which may be particularly suitable for geriatric patients OBJECTIVE : To evaluate the efficacy of two vaginal doses of estradiol ( E2 ) compared with placebo in the treatment of atrophic vaginitis . METHODS : In a multi-center , r and omized , double-blind , parallel-group study , 230 postmenopausal women received treatment with 25 mcg or 10 mcg E2 or placebo for 12 weeks . Efficacy was measured through composite score of three vaginal symptoms and grading of vaginal health . Additional analyses included maturation of vaginal and urethral mucosa . Safety assessment s included endometrial biopsy , adverse events , changes in laboratory tests , and physical examinations . After 12 weeks of treatment , all patients were switched to the open-label extension and received treatment with 25 mcg E2 up to week 52 . RESULTS : Vaginal tablets with 25 mcg and 10 mcg E2 showed significant ( P<.001 ) improvement in composite score of vaginal health . Other results with 10 mcg E2 were not entirely consistent with those for 25 mcg E2 . Over 12 weeks , both active treatments result ed in greater decreases in vaginal pH than placebo . There were no significant differences between the 25 mcg and 10 mcg E2 groups in terms of improvements in maturation value or composite score of three vaginal symptoms . The efficacy was maintained to week 52 with 25 mcg E2 . CONCLUSION : Vaginal tablets with 25 mcg and 10 mcg E2 provided relief of vaginal symptoms , improved urogenital atrophy , decreased vaginal pH , and increased maturation of the vaginal and urethral epithelium . Those improvements were greater with 25 mcg than with 10 mcg E2 . Both doses were effective in the treatment of atrophic vaginitis . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00465192 and NCT00464971 LEVEL OF EVIDENCE : Objective : The aim of this study was to evaluate the efficacy and safety of low-dose conjugated estrogens ( CE ) cream for treatment of atrophic vaginitis . Methods : Postmenopausal women ( N = 423 ) with moderate-to-severe vaginal atrophy were r and omized to CE cream 0.3 mg or placebo once daily ( 21 days on/7 days off ) or twice weekly for 12 weeks , followed by open-label treatment with CE cream for 40 weeks consistent with their prior regimen . Primary endpoints were changes in vaginal maturation index ( VMI ; percentage of superficial cells ) , vaginal pH , and severity of participant-reported most bothersome symptom ( vaginal dryness , itching , burning , or dyspareunia ) at week 12 . Endometrial safety was assessed by transvaginal ultrasound and endometrial biopsy for 52 weeks . Results : At week 12 , improvements in VMI with daily and twice-weekly use of low-dose CE cream ( 27.9 % and 25.8 % , respectively ) were significantly greater compared with placebo ( 3.0 % and 1.0 % , respectively ; P < 0.001 ) . Improvements in vaginal pH with daily and twice-weekly CE cream ( −1.6 for both ) were also significantly greater relative to placebo ( −0.4 and −0.3 , respectively ; P < 0.001 ) . VMI and vaginal pH responses were sustained through 52 weeks . Both CE cream regimens significantly reduced most bothersome symptom scores compared with placebo ( P ≤ 0.001 ) , including those for dyspareunia ( P ≤ 0.01 ) . There was no report of endometrial hyperplasia or carcinoma . Adverse events occurred with similar frequency among the active and placebo groups during the double-blind phase . Conclusions : Daily and twice-weekly use of low-dose CE cream was equally effective in relieving symptoms of vulvovaginal atrophy . Both regimens showed endometrial safety and sustained efficacy during 1 year of therapy Objective To assess the efficacy and safety of intravaginal estriol administration on urinary incontinence , urogenital atrophy , and recurrent urinary tract infections in postmenopausal women . Design Eighty-eight postmenopausal women with urogenital aging symptoms were enrolled in this prospect i ve , r and omized , placebo-controlled study . Participants were r and omly divided into two groups , with each group consisting of 44 women . Women in the treatment group received intravaginal estriol ovules : 1 ovule ( 1 mg ) once daily for 2 weeks and then 2 ovules once weekly for a total of 6 months as maintenance therapy . Women in the control group received inert placebo vaginal suppositories in a similar regimen . We evaluated urogenital symptomatology , urine cultures , colposcopic findings , urethral cytologic findings , urethral pressure profiles , and urethrocystometry before as well as after 6 months of treatment . Results After therapy , the symptoms and signs of urogenital atrophy significantly improved in the treatment group in comparison with the control group . Thirty ( 68 % ) of the treated participants , and only seven ( 16 % ) of the control participants registered a subjective improvement of their incontinence . In the treated participants , we observed significant improvements of colposcopic findings , and there were statistically significant increases in mean maximum urethral pressure , in mean urethral closure pressure as well as in the abdominal pressure transmission ratio to the proximal urethra . Urethrocystometry showed positive but not statistically significant modifications . Conclusions Our results show that intravaginal administration of estriol may represent a satisfactory therapeutic choice for those postmenopausal women with urogenital tract disturbances who have contraindications or refuse to undergo st and ard hormone therapy Fifty-one post-menopausal women suffering from symptoms of oestrogen deficiency-derived atrophic vaginitis were treated intravaginally with two therapeutic regimens based on doses of 25 micrograms 17 beta-oestradiol ( E2 ) in an open , controlled study . All the patients received treatment daily for 2 weeks by way of induction therapy . They were then r and omly allocated to either once-weekly ( 17 patients ) or twice-weekly ( 34 patients ) vaginal administration for a further 50 weeks as maintenance treatment . Endometrial histopathology was evaluated before and after 1 year of treatment . The effects on symptoms and oestrogen/gonadotrophin levels were determined before and after 2 , 12 , 24 , 36 and 52 weeks of therapy . Nine women continued twice-weekly treatment for a further year , meaning that they underwent treatment for a total period of 2 years . Endometrial biopsies were obtained after 2 years of treatment . All the pretreatment endometrial biopsies indicated an atrophic endometrium . One patient out of the 14 who completed 1 year of therapy in the group treated once weekly showed weak proliferation of the endometrium , while the other 13 had an atrophic endometrium . In the group treated twice weekly , 2 out of the 31 patients who completed the study showed weak proliferation of the endometrium . The other 29 had an atrophic endometrium . All 9 women who received treatment for 2 years had an atrophic endometrium at the end of the treatment period . The twice-weekly dosage regimen gave complete relief of symptoms in almost all patients , whereas the majority of the patients in the group treated once weekly still had mild symptoms . No adverse effects were reported . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE The objective of this study was to compare the efficacy of locally administered low-dose estrogens ( 0.625 mg of conjugated estrogens ) and orally administered tibolone in postmenopausal women with symptoms and signs of atrophic vaginitis . Vaginal ultrasound was performed for the evaluation of endometrial or ovarian abnormalities . METHODS A 6-month comparative r and omised prospect i ve study of women taking tibolone and locally administered low-dose estrogens . Seventy two postmenopausal women with symptoms of atrophic vaginitis were examined with vaginal ultrasound . The endometrial thickness , the endometrial volume , the uterus and the ovaries were measured before and after 6 months of treatment with low-dose estrogens or tibolone . RESULTS In group A ( low-dose estrogens treatment ) the mean endometrial thickness , before and after treatment , was 3.0 + /- 0.1 mm and 2.9 + /- 0.8 mm , respectively . The mean ovarian volume was 3.9 ml . There were no changes in uterine volume during the treatment period . In group B ( treated with tibolone ) endometrial thickness was 3.2 + /- 0.3 mm and 3.2 + /- 0.7 mm , respectively . One women experienced vaginal bleeding . The volume of corpus uteri was unchanged after treatment . The volume of both ovaries was 4.2 ml and 3.9 ml , respectively . The overall acceptability of both types of administration was good . CONCLUSIONS This study , using vaginal ultrasound , has shown that either hormone replacement therapy with tibolone or symptomatic treatment with low-dose estrogens , gives no sign of endometrial proliferation measured as endometrial thickness Vaginal atrophy can be reversed for most women through systemic hormones . Those women who can not take systemic hormones can get relief of symptoms with local estrogen therapy , which ideally should be locally effective without significant systemic absorption and without endometrial stimulation . An estradiol-releasing vaginal ring was therefore tested for efficacy , safety and patient acceptability in a 15-week open-label , r and omized parallel group trial with blinded evaluations of the cytological response data . Conjugated estrogen vaginal cream was used as a reference control . The primary objectives of the study were to evaluate whether the two treatments were equivalent regarding improvement in urogenital atrophy , improvement in physicians 's overall evaluation of product performance on urinary and /or vaginal changes , and improvement in patient 's assessment of urinary and /or vaginal symptoms . A secondary objective was to assess frequency of endometrial overstimulation during estrogen replacement therapy , to be measured by a progestogen challenge test . The ring and cream treatment produced an equivalent effect on the vaginal mucosa , and equivalence was also found in physician 's and patient 's assessment s of both vaginal and urinary symptomatology . Both treatments were equally effective in improving the vaginal pH toward levels normally seen in fertile women ( < 5.0 ) . With regard to end Output:	Compared with placebo , vaginal estrogens improved dryness , dyspareunia , urinary urgency , frequency , and stress urinary incontinence ( SUI ) and urgency urinary incontinence ( UUI ) . Urinary tract infection rates decreased . The various estrogen preparations had similar efficacy and safety ; serum estradiol levels remained within postmenopausal norms for all except high-dose conjugated equine estrogen cream . Endometrial hyperplasia and adenocarcinoma were extremely rare among those receiving vaginal estrogen . Comparing vaginal estrogen with nonhormonal moisturizers , patients with two or more symptoms of vulvovaginal atrophy were substantially more improved using vaginal estrogens , but those with one or minor complaints had similar symptom resolution with either estrogen or nonhormonal moisturizer . : All commercially available vaginal estrogens effectively relieve common vulvovaginal atrophy-related complaints and have additional utility in patients with urinary urgency , frequency or nocturia , SUI and UUI , and recurrent UTIs . Nonhormonal moisturizers are a beneficial alternative for those with few or minor atrophy-related symptoms and in patients at risk for estrogen-related neoplasia .
MS22515	*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 Latent trigger points in the upper trapezius muscle may disrupt muscle movement patterns and cause problems such as cramping and decreased muscle strength . Because latent trigger points may spontaneously become active trigger points , they should be addressed and treated to prevent further problems . In this study we compared the short-term effect of kinesiotaping versus friction massage on latent trigger points in the upper trapezius muscle . Methods Fifty-eight male students enrolled with a stratified sampling method participated in this single-blind r and omized clinical trial ( Registration ID : I RCT 2016080126674N3 ) in 2016 . Pressure pain threshold was recorded with a pressure algometer and grip strength was recorded with a Collin dynamometer . The participants were r and omly assigned to two different treatment groups : kinesiotape or friction massage . Friction massage was performed daily for 3 sessions and kinesiotape was used for 72 h. One hour after the last session of friction massage or removal of the kinesiotape , pressure pain threshold and grip strength were evaluated again . Results Pressure pain threshold decreased significantly after both friction massage ( 2.66 ± 0.89 to 2.25 ± 0.76 ; P = 0.02 ) and kinesiotaping ( 2.00 ± 0.74 to 1.71 ± 0.65 ; P = 0.01 ) . Grip strength increased significantly after friction massage ( 40.78 ± 9.55 to 42.17 ± 10.68 ; P = 0.03 ) ; however there was no significant change in the kinesiotape group ( 39.72 ± 6.42 to 40.65 ± 7.3 ; P = 0.197 ) . There were no significant differences in pressure pain threshold ( 2.10 ± 0.11 & 1.87 ± 0.11 ; P = 0.66 ) or grip strength ( 42.17 ± 10.68 & 40.65 ± 7.3 ; P = 0.53 ) between the two study groups . Conclusions Friction massage and kinesiotaping had identical short-term effects on latent trigger points in the upper trapezius . Three sessions of either of these two interventions did not improve latent trigger points . Trial registration Registration ID in I RCT : I RCT 2016080126674N3 Study Design : R and omized clinical trial . Introduction : KinesioTape ( KT ) is a noninvasive method to treat pain and muscular dysfunction . Purpose : To investigate the effect of KT with and without tension on pain intensity , pain pressure threshold , grip strength and disability in individuals with lateral epicondylitis , and myofacial trigger points in forearm muscles . Methods : Thirty women with lateral epicondylitis and myofacial trigger point in forearm muscles were r and omly assigned to KT with tension and placebo ( KT without tension ) . The treatment was provided 3 times in one week , and outcome measures were assess pre‐post treatment . Results : The mean score of visual analogue scale ( VAS ) during activity decreased significantly from 6.4 and 6 pretest to 2.53 and 4.66 posttest , respectively , for the KT with and without tension groups . The mean score of Disabilities of the Arm , Shoulder and H and decreased significantly from 16.82 and 22.79 pretest to 8.65 and 8.29 posttest , respectively , for the KT with and without tension groups . A paired t‐test revealed a significant reduction in VAS during activity and Disabilities of the Arm , Shoulder and H and before and after treatment in both groups ( P < .05 ) . Pain pressure threshold , grip strength , and VAS using an algometer revealed no significant differences . The study showed no significant difference in variables immediately after intervention . Discussion : Improvements in functional disability were superior when KT was used with tension , than obtained with a placebo‐no tension application . Conclusion : The application of KT produces an improvement in pain intensity and upper extremity disability in subjects with LE and MTP in forearm muscles , and KT with tension was more effective than placebo group . Level of Evidence : NA . Trial Registration Number : 100‐216 [ Purpose ] The purpose of this study was to identify the changes in the myofascial pain and range of the motion of temporom and ibular joint when Kinesio taping is applied to patients with latent myofascial trigger points of the sternocleidomastoid muscle . [ Subjects and Methods ] The subjects were 42 males and females aged 20 to 30 years ( male 17 , female 25 ) . They were r and omly divided into the control group and the experimental group , which would receive Kinesio taping . Kinesio taping was applied to the sternocleidomastoid muscle three times per week for two weeks . The pain triggered when the taut b and or nodule was palpated was measured . Pain intensity was measured using the visual analog scale ( VAS ) and pressure pain threshold ( PPT ) . The range of motion of the temporom and ibular joint was measured . In all subjects , VAS , PPT , and range of motion of the temporom and ibular joint were measured before and after the intervention . [ Results ] In the experimental group , it was found that pain in the SCM was relived , as the VAS and PPT score decrease significantly and range of motion of temporom and ibular joint increase significantly . In comparison between the groups , significant differences were shown in the VAS and PPT scores and in the range of motion of the temporom and ibular joint . [ Conclusion ] Kinesio taping is thought to be an intervention method that can be applied to latent myofascial trigger points STUDY DESIGN R and omized controlled trial . INTRODUCTION Myofascial pain syndrome is characterized by myofascial trigger points ( MTrPs ) and fascia tenderness . PURPOSE OF THE STUDY We investigated the effects of manual pressure release ( MPR ) alone or in combination with taping ( MPR/MKT ) in subjects with MTrPs . METHODS Fifteen and 16 subjects received MPR and MPR/MKT respectively . Outcomes including Pressure pain threshold , muscle stiffness , mechanomyography were assessed at baseline , post-intervention and 7-days later . RESULTS Pressure pain threshold improved significantly ( d = 1.79 , p < 0.005 ) in both groups . Significant improvement in muscle stiffness in the MPR/MKT group ( 0.27 - 0.49 mm ) as compared to the MPR group ( -0.02 - 0.23 mm ) . Mechanomyography amplitude in the MPR/MKT group was significantly higher than that of the MPR group ( p < 0.05 ) . CONCLUSION MPR and MPR/MKT are effective in reducing pain in these subjects . MPR/MKT has a greater effect on muscle stiffness and contraction amplitude . LEVEL OF EVIDENCE IV OBJECTIVES Verbally administered numerical rating scales ( NRSs ) from 0 to 10 are often used to measure pain , but they have not been vali date d in the emergency department ( ED ) setting . The authors wished to assess the comparability of the NRS and visual analog scale ( VAS ) as measures of acute pain , and to identify the minimum clinical ly significant difference in pain that could be detected on the NRS . METHODS This was a prospect i ve cohort study of a convenience sample of adults presenting with acute pain to an urban ED . Patients verbally rated pain intensity as an integer from 0 to 10 ( 0 = no pain , 10 = worst possible pain ) , and marked a 10-cm horizontal VAS bounded by these descriptors . VAS and NRS data were obtained at presentation , 30 minutes later , and 60 minutes later . At 30 and 60 minutes , patients were asked whether their pain was " much less , " " a little less , " " about the same , " " a little more , " or " much more . " Differences between consecutive pairs of measurements on the VAS and NRS obtained at 30-minute intervals were calculated for each of the five categories of pain descriptor . The association between VAS and NRS scores was expressed as a correlation coefficient . The VAS scores were regressed on the NRS scores in order to assess the equivalence of the measures . The mean changes associated with descriptors " a little less " or " a little more " were combined to define the minimum clinical ly significant difference in pain measured on the VAS and NRS . RESULTS Of 108 patients entered , 103 provided data at 30 minutes and 86 at 60 minutes . NRS scores were strongly correlated to VAS scores at all time periods ( r = 0.94 , 95 % CI = 0.93 to 0.95 ) . The slope of the regression line was 1.01 ( 95 % CI = 0.97 to 1.06 ) and the y-intercept was -0.34 ( 95 % CI = -0.67 to -0.01 ) . The minimum clinical ly significant difference in pain was 1.3 ( 95 % CI = 1.0 to 1.5 ) on the NRS and 1.4 ( 95 % CI = 1.1 to 1.7 ) on the VAS . CONCLUSIONS The findings suggest that the verbally administered NRS can be substituted for the VAS in acute pain measurement BACKGROUND Although there are several studies of Transcutaneous Electrical Nerve Stimulation ( TENS ) and exercise in myofascial pain syndrome , there are no studies comparing the effectiveness of Kinesio Taping ( KT ) and TENS in myofascial pain syndrome patients . OBJECTIVE To compare the early and late effects of TENS and KT on pain , disability and range of motion in myofascial pain syndrome patients . METHODS Sixty-nine patients were divided into three groups r and omly as TENS+Exercise , KT+Exercise and exercise groups . Visual Analogue Scale ( VAS ) , pain threshold , Neck Disability Index and cervical contralateral lateral flexion were employed in the evaluation of the patients performed before treatment , after treatment and 3rd month after treatment . RESULTS The VAS , pain threshold , Neck Disability Index and contralateral lateral flexion values were improved in all groups both in after treatment and 3rd month after treatment ( p < 0.01 ) . In the comparison of after treatment vs. before treatment evaluations , VAS score was decreased in KT group compared to the TENS and control group ( p= 0.001 ) , in the TENS group compared to control group ( p= 0.011 ) . In the comparison of 3rd month and before treatment evaluations , VAS score was decreased in the TENS group compared to control group ( p= 0.001 ) and in the KT group compared to the control group ( p= 0.001 ) . There was no significant difference between TENS and KT groups . All other parameters did not differ between the groups . CONCLUSIONS TENS and KT added exercises can decrease pain severity and increase pain threshold , function and cervical range of motion in myofascial pain syndrome patients . Addition of TENS or KT to the exercise therapy result ed in more significant improvement compared to exercise therapy alone with a more pronounced improvement in KT group compared to the TENS group in the early period . Because KT was found to be more effective in decreasing the pain and had the advantage of being used in every 3 days , it seems to be beneficial in acute painful periods in myofascial pain syndrome patients Objective To investigate the histopathological nature of myofascial trigger points ( MTrPs ) or spots ( MTrSs ) at different stages of recovery from injury in a rat model . Methods Forty Sprague – Dawley rats were r and omly divided into two groups : a control group ( CG ) and experimental group ( EG ) . The CG was further r and omly subdivided into CG1 and CG2 subgroups . The CG2 was used for palpating the taut b and and CG1 as a blank . EG was subdivided into three groups according to recovery times : 4 weeks ( 4W ) , 8 weeks ( 8W ) and 12 weeks ( 12W ) ; these groups consisted of eight rats each . All CG rats received no intervention , whereas the intervention in EG rats was by a blunt strike to the vastus medialis and eccentric exercise for 8 weeks . The taut b and s with spontaneous electrical activity were then detected in the muscle to guide a muscle biopsy . The histopathological findings were investigated under optical and electron microscopes in all groups . Results Under optical microscopy , the differently augmented sizes of round fibres ( contracture knots ) with deep staining in the transverse section and fusiform shapes in a longitudinal view were clearly seen in CG2 and EGs with a large diameter ; the number of contracture knots was significantly more in EGs than in CGs . Under an electron microscope , the mitochondria in EGs significantly decreased with abnormal structures . The sarcomeres were significantly shortened in the 8W and 12W EGs . Conclusion An injury can cause activation of MTrSs in a muscle and an activated level of MTrPs depending on the number of contracture knots in muscle with impaired energy production Objective The aims of this study are to investigate the changes in spontaneous electrical activities ( SEAs ) and in acetylcholine ( ACh ) , acetylcholine receptor ( AChR ) , and acetylcholine esterase ( AChE ) levels after dry needling at myofascial trigger spots in model rats . Material s and Methods Forty-eight male Sprague-Dawley rats were divided into four groups . Thirty-six rats were assigned to three model groups , which underwent MTrSs modeling intervention . Twelve rats were assigned to the blank control ( BC ) group . After model construction , the 36 model rats were r and omly subdivided into three groups according to treatment : M Output:	However , there was no detectable effect on disability or function . Conclusion : Statistical evidence showed that kinesio taping could be recommended to relieve pain intensity and range of motion for patients with myofascial pain syndrome at post-intervention
MS22516	*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 : Some argued that clinical efficacy of Chondroitin Sulfate ( CS ) could vary upon the product origin . The objective of this trial is to compare the effect of 2 CS medicinal products from different origin : Structum ® ( avian , 1000mg/day ) and Chondrosulf ® ( bovine , 1200mg/day ) . Methods : This was a r and omized , double-blind , double placebo , active-controlled , parallel-group study using a non-inferiority design . Symptomatic osteoarthritis of the knee patients , according to American College of Rheumatology criteria , aged 50 - 80 years received either Structum ® ( 500 mg BID ) or Chondrosulf ® ( 400 mg TID ) during 24 weeks . Inclusion criteria were : global pain in the target knee ≥ 40 mm on a Visual Analog Scale ( VAS 0 - 100 ) , a Lequesne ’s Algofunctional Index ( LFI ) score ≥ 7 ( range : 0 - 24 ) and a radiological Kellgren-Lawrence grade 2 or 3 . Primary outcome was the mean change over 24 weeks of pain VAS and LFI score . Secondary outcomes were patient ’s and physician ’s global assessment s , Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International responders rate , analgesics intake and Medical Outcomes Survey Short-Form 12 ( SF-12 ) . Safety was assessed by recording adverse events . A non-inferiority test was performed on the Structum ® -Chondrosulf ® difference for VAS and LFI score changes . Predefined non inferiority limit was settled as the lower limit of the 95 % CI above -5 mm and -1pt for pain VAS and LFI score respectively . Results : 837 patients were r and omized : 817 available for the full analysis data set ( FAS ) , 692 for the per protocol ( PP ) analysis . No statistical and clinical differences were observed for demographics and disease characteristics between the 2 groups . PP analysis showed no difference between groups on mean variations of pain VAS or LFI scores over 24 weeks . Mean Pain VAS decreased by 23.9 mm ( 17.5 ) in Structum ® group and 23.8 mm ( 17.2 ) in Chondrosulf ® group ( difference : 0.012 [ CI95 % : -2.6 ; 2.6 ] ) . Mean LFI score decreased by 3.2 ( 2.4 ) and 3.1 ( 2.4 ) respectively ( difference : 0.139 [ CI95 % : -0.2 ; 0.5 ] ) . The lower limits of the 2 CI were above predefined non inferiority margin , which demonstrated the non inferiority of Structum ® in comparison with Chondrosulf ® . FAS analysis gave similar results . Secondary efficacy outcomes analysis showed the same trends . Responders rate were 76.3 % and 73.8 % respectively ( PP , W24 ) . Treatments were well tolerated : 2.4 % in Structum ® group and 4.5 % in Chondrosulf ® group withdrew from the study for safety reasons . Conclusion : Structum ® and Chondrosulf ® were equally effective in reducing functional impairment and relieving pain over 6 months in knee osteoarthritis patients , without any safety concerns . Trial Registration : http://www.controlled-trials.com Number : IS RCT N04305346 BACKGROUND Glucosamine and chondroitin sulfate are used to treat osteoarthritis . The multicenter , double-blind , placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial ( GAIT ) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis . METHODS We r and omly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily , 1200 mg of chondroitin sulfate daily , both glucosamine and chondroitin sulfate , 200 mg of celecoxib daily , or placebo for 24 weeks . Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia . Assignment was stratified according to the severity of knee pain ( mild [ N=1229 ] vs. moderate to severe [ N=354 ] ) . The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24 . RESULTS The mean age of the patients was 59 years , and 64 percent were women . Overall , glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent . As compared with the rate of response to placebo ( 60.1 percent ) , the rate of response to glucosamine was 3.9 percentage points higher ( P=0.30 ) , the rate of response to chondroitin sulfate was 5.3 percentage points higher ( P=0.17 ) , and the rate of response to combined treatment was 6.5 percentage points higher ( P=0.09 ) . The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group ( P=0.008 ) . For patients with moderate-to-severe pain at baseline , the rate of response was significantly higher with combined therapy than with placebo ( 79.2 percent vs. 54.3 percent , P=0.002 ) . Adverse events were mild , infrequent , and evenly distributed among the groups . CONCLUSIONS Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee . Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain . ( Clinical Trials.gov number , NCT00032890 . ) OBJECTIVE To evaluate the symptomatic effects of highly purified chondroitin 4 and chondroitin 6 sulfate ( CS ) therapy in patients with osteoarthritis ( OA ) of the h and . METHODS This investigator-initiated , single-center , r and omized , double-blind , placebo-controlled clinical trial included 162 symptomatic patients with radiographic evidence of h and OA ( American College of Rheumatology criteria ) . Inclusion criteria included patient 's assessment of global spontaneous h and pain of at least 40 mm on a 0 - 100-mm visual analog scale ( VAS ) and functional impairment of at least 6 ( 0 - 30 scale ) on the Functional Index for H and OA ( FIHOA ) in the most symptomatic h and . Patients received either 800 mg of CS ( n = 80 patients ) or placebo ( n = 82 patients ) once daily for 6 months and were analyzed in an intent-to-treat approach . The two primary outcomes were the change in the patient 's assessment of global spontaneous h and pain and in h and function ( by FIHOA score ) from baseline to month 6 . Secondary outcomes were improvement in grip strength , duration of morning stiffness , acetaminophen consumption , and the investigator 's global impression of treatment efficacy . RESULTS There was a significantly more pronounced decrease in the patient 's global assessment of h and pain in the CS group than in the placebo group ( difference VAS scores -8.7 mm ; P = 0.016 ) . H and function improved significantly more in the CS group than in the placebo group ( difference in FIHOA scores -2.14 ; P = 0.008 ) . There was a statistically significant between-group difference in favor of CS for the duration of morning stiffness and for the investigator 's global impression of treatment efficacy . Changes in grip strength , acetaminophen consumption , and safety end points were not significantly different between the two groups . CONCLUSION This study demonstrates that CS improves h and pain and function in patients with symptomatic OA of the h and and shows a good safety profile AIM To determine the minimum clinical ly important difference ( MCID ) in joint space width ( JSW ) progression in patients with hip osteoarthritis ( OA ) , based upon evaluation by a panel of clinical experts as a gold st and ard . METHODS A sample of 298 patients with hip OA was selected from a multicentre , prospect i ve , longitudinal , 3-yr follow-up study . A pelvic radiograph was obtained at entry and after 3 yr . For each film , the narrowest JSW was measured using a 0.1-mm graduated magnifying glass . The difference between baseline and 3-yr follow-up JSW was calculated . Two senior rheumatologists , who were experts in osteoarthritis , evaluated each pair of films and noted whether a clinical ly relevant deterioration in osteoarthritis stage occurred at 3 yr compared with baseline . Interobserver reliabilities were evaluated using the kappa coefficient and proportions of agreements . Then , for each measured difference in JSW ( 0.1 mm per 0.1 mm ) , the sensitivity and specificity for MCID , defined as the assessment of expert 1 , expert 2 or a combination of both , were calculated . This allowed us to obtain , from graphic representations of the correct classification probabilities , the best measured JSW threshold , with the maximal true positive and the minimal false positive results . RESULTS The mean measured change in JSW was -0.63 + /- 0.74 mm . Experts 1 and 2 considered the decrease in JSW to be clinical ly relevant in 122 ( 40.9 % ) and 100 pairs ( 33.6 % ) respectively . The proportion of agreements between the experts was 79.9 % , with a kappa coefficient of 0.572 . The best measured JSW threshold was -0.4 mm for expert 1 , expert 2 and the combination of both ; sensitivity and specificity were 0.75 and 0.8 , 0.71 and 0.72 , and 0.75 and 0.7 respectively . CONCLUSION This study suggests that a change of at least 0.4 mm in the radiological JSW could be considered clinical ly relevant . Other studies using other sets of patients and other methods are needed for validation Objective To determine the effect of chondroitin sulphate ( CS ) treatment on cartilage volume loss , subchondral bone marrow lesions ( BML ) , synovitis and disease symptoms in patients with knee osteoarthritis ( OA ) . Methods In this pilot multicentre , r and omised , double-blind , controlled trial in primary knee OA , 69 patients with clinical signs of synovitis were r and omised to receive CS 800 mg or placebo once daily for 6 months followed by an open-label phase of 6 months in which patients in both groups received CS 800 mg once daily . Cartilage volume and BML were assessed by MRI at baseline and at 6 and 12 months ; synovial membrane thickness was assessed at baseline and at 6 months . Results The CS group showed significantly less cartilage volume loss than the placebo group as early as 6 months for the global knee ( p=0.030 ) , lateral compartment ( p=0.015 ) and tibial plateaus ( p=0.002 ) , with significance persisting at 12 months . Significantly lower BML scores were found for the CS group at 12 months in the lateral compartment ( p=0.035 ) and the lateral femoral condyle ( p=0.044 ) . Disease symptoms were similar between the two groups . Conclusion CS treatment significantly reduced the cartilage volume loss in knee OA starting at 6 months of treatment , and BML at 12 months . These findings suggest a joint structure protective effect of CS and provide new in vivo information on its mode of action in knee OA BACKGROUND Osteoarthritis ( OA ) is the most common joint disease encountered throughout Europe . A task force for the EULAR St and ing Committee for Clinical Trials met in 1998 to determine the method ological and logistical approach required for the development of evidence based guidelines for treatment of knee OA . The guidelines were restricted to cover all currently available treatments for knee OA diagnosed either clinical ly and /or radiographically affecting any compartment of the knee . METHODS The first stage was the selection of treatment modalities to be considered . The second stage comprised a search of the electronic data bases Medline and Embase using a combination of subject headings and keywords . All European language publications in the form of systematic review s , meta-analyses , r and omised controlled trials , controlled trials , and observational studies were included . During stage three all the relevant studies were quality scored . The summary statistics for vali date d outcome measures , when available , were recorded and , where practical , the numbers needed to treat and the effect size for each treatment were calculated . In the fourth stage key clinical propositions were determined by expert consensus employing a Delphi approach . The final stage ranked these propositions according to the available evidence . A second set of propositions relating to a future research agenda was determined by expert consensus using a Delphi approach . RESULTS Over 2400 English language publications and 400 non-English language publications were identified . Seven hundred and forty four studies presented outcome data of the effects of specific treatments on knee OA . Quantitative analysis of treatment effect was possible in only 61 studies . Recommendations for the management of knee OA based on currently available data and expert opinion are presented . Proposals for a future research agenda are highlighted . CONCLUSIONS These are the first clinical guidelines on knee OA to combine an evidence based approach and a consensus approach across a wide range of treatment modalities . It is apparent that certain clinical propositions are supported by substantial research based evidence , while others are not . There is thus an urgent need for Output:	Chondroitin did not result in statistically significant numbers of adverse events or withdrawals due to adverse events compared with placebo or another drug . The beneficial effects of chondroitin in pain and Lequesne 's index persisted when evidence was limited to studies with adequate blinding or studies that used appropriate intention to treat ( ITT ) analyses . These beneficial effects were uncertain when we limited data to studies with appropriate allocation concealment or a large study sample ( > 200 ) or to studies without pharmaceutical funding . A review of r and omized trials of mostly low quality reveals that chondroitin ( alone or in combination with glucosamine ) was better than placebo in improving pain in participants with osteoarthritis in short-term studies . Chondroitin had a lower risk of serious adverse events compared with control . The combination of some efficacy and low risk associated with chondroitin may explain its popularity among patients as an over-the-counter supplement
MS22517	*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 study is to compare the remission and complication rates of actinomycin D ( Act-D ) and methotrexate-folinic acid ( MTX-FA ) as single-agent treatments of stage I , low-risk gestational trophoblastic neoplasia ( GTN ) . From 1994 to 2005 , all women with International Federation of Gynecology and Obstetrics stage I , low-risk GTN were r and omly assigned to received either intravenous Act-D 10 & mgr;g/kg per day for 5 days every 2 weeks or intramuscular methotrexate 1 mg/kg per day on days 1 , 3 , 5 , and 7 with intramuscular folinic acid 0.1 mg/kg per day on days 2 , 4 , 6 , and 8 every 2 weeks . Forty-nine women met the eligibility criteria . Age , human chorionic gonadotropin level , and International Federation of Gynecology and Obstetrics score were similar in both treatment groups . Of the 22 women who received Act-D , 2 were lost to follow-up . Among the 27 women who received MTX-FA , 2 were lost to follow-up , and 6 had to switch to Act-D because of the rising levels of liver enzymes . All 20 women ( 100 % ) in the Act-D arm achieved remission compared with 14 ( 73.6 % ) in 19 women in the MTX-FA arm ( P = 0.02 ) . Mucositis and alopecia were reported more frequently in the Act-D group , whereas elevations of liver enzyme levels were more frequent in the MTX-FA group . Actinomycin D seems to be more effective than MTX-FA in the treatment of stage I , low-risk GTN . Larger multicenter r and omized controlled trials should be conducted to establish the most appropriate regimen for these patients OBJECTIVE To evaluate the efficacy of the FAEV regimen ( floxuridine , actinomycin D , etoposide , vincristine ) in the treatment of high-risk , drug-resistant gestational trophoblastic tumor ( GTT ) . STUDY DESIGN From October 2001 to May 2004 , 11 cases of high-risk , drug-resistant GTT were treated with the FAEV regimen . All cases were referred to Peking Union Medical College Hospital because of previous failure of chemotherapy . The patients ' ages ranged from 21 to 60 ( median , 32 ) years . The International Federation of Gynecologists and Obstetricians score was 7 - 13 ( median , 9 ) . All cases were followed for 15 - 42 months after FAEV treatment . RESULTS Seven cases ( 63.6 % , 7 of 11 ) were cured by the FAEV regimen . The median course number for serum human chorionic gonadotropin reaching a normal level was 3 . Four cases ( 36 % , 4 of 11 ) showed drug resistance to the FAEV regimen . The major side effect of FAEV regimen is myelosuppression . Granulocyte colony-stimulating factor support was needed after 98.4 % ( 63 of 64 ) of the courses . CONCLUSION For high-risk , drug-resistant GTT cases , FAEV regimen could be an effective treatment OBJECTIVE To evaluate the results of etoposide/ methotrexate/actinomycin D/etoposide/cisplatin ( EMA/ EP ) chemotherapy in patients with chemorefractory gestational trophoblastic tumor ( GTT ) . STUDY DESIGN Fifteen patients with chemorefractory GTT were treated with EMA/EP . RESULTS Twelve of the 15 cases were choriocarcinoma , and the last 3 were metastatic placental site trophoblastic tumor ( PSTT ) : International Federation of Gynecology and Obstetrics ( FIGO ) stage I , 2 cases ; stage III , 10 cases ; stage IV , 3 cases . Seven cases have FIGO score 7 - 10 ; the scores of the remaining 8 cases were > 10 . Fifteen patients received a total of 93 cycles of the study regimen . The median number of courses for each patient was 6.2 . Eleven cases ( 73.3 % ) achieved complete remission , while 3 ( 20 % ) had partial remission ; 1 case ( 6.7 % ) showed no response . The main complications of EMA/EP chemotherapy were myelosuppression and gastrointestinal symptoms . CONCLUSION The EMA/EP regimen is effective for chemorefractory GTT , and the chemotherapeutic results can be improved when combined with surgery and arterial infusion chemotherapy in selected patients . The EMA/EP regimen should be considered for primary management of metastatic PSTT PURPOSE There is no consensus on the best regimen for the primary treatment of low-risk gestational trophoblastic neoplasia ( GTN ) . PATIENTS AND METHODS Two commonly used single-drug regimens were compared with respect to the proportion of patients meeting the criteria for a complete response ( CR ) in a r and omized phase III trial conducted by the Gynecologic Oncology Group . Eligibility was purpose fully broad to maximize the generalizability of the results and included patients with a WHO risk score of 0 to 6 and patients with metastatic disease ( limited to lung lesions < 2 cm , adnexa , or vagina ) or choriocarcinoma . RESULTS Two hundred forty women were enrolled , and 216 were deemed eligible . Biweekly intravenous dactinomycin 1.25 mg/m² was statistically superior to weekly intramuscular ( IM ) methotrexate 30 mg/m² ( CR : 70 % v 53 % ; P = .01 ) . Similarly , in patients with low-risk GTN as defined before the 2002 WHO risk score revisions ( risk score of 0 to 4 and excluding choriocarcinoma ) , response was 58 % and 73 % in the methotrexate and dactinomycin arms , respectively ( P = .03 ) . Both regimens were less effective if the WHO risk score was 5 or 6 or if the diagnosis was choriocarcinoma ( CR : 9 % and 42 % , respectively ) . There were two potential recurrences ; one at 4 months ( dactinomycin ) and one at 22 months ( methotrexate ) . Not all patients completed follow-up . Both regimens were well tolerated . CONCLUSION The biweekly dactinomycin regimen has a higher CR rate than the weekly IM methotrexate regimen in low-risk GTN , a generally curable disease OBJECTIVE To compare the efficacy of methotrexate and actinomycin D as single agents in first-line chemotherapy for women with low-risk gestational trophoblastic neoplasia ( LR-GTN ) . METHODS A total of 131 women with LR-GTN were r and omized to receive a weekly pulsed dose of 30 mg/m(2 ) of methotrexate intramuscularly ( n=81 ) or a pulsed intravenous bolus of 1.25 mg/m(2 ) of actinomycin D every 2 weeks ( n=50 ) . An additional cycle was administered as consolidation treatment following normalization of the serum level of beta-human chorionic gonadotropin ( < 5 IU/L ) . RESULTS Complete remission was achieved in 48.14 % of patients in the methotrexate group and 90.00 % in the actinomycin D group ( P<0.001 ) . The mean number of treatment cycles needed to achieve response was lower in the actinomycin D group ( 4.8 vs 6.8 ) . The risk of treatment failure was 26.4 greater with methotrexate than with actinomycin D ( 95 % confidence interval , 5.7 - 22.6 ; P<0.001 ) . CONCLUSION Actinomycin D may be a better option than methotrexate as a first-line chemotherapy agent for patients with LR-GTN The purpose of the study was to determine the activity and toxicity of pulse dactinomycin as salvage treatment of patients with low‐risk gestational trophoblastic neoplasia ( GTN ) who failed methotrexate therapy OBJECTIVE To evaluate the efficacy and safety of etoposide/methotrexate/actinomycin D ( MEA regimen ) as initial chemotherapy and 5-fluorouracil/actinomycin D ( FA regimen ) as salvage chemotherapy for high-risk gestational trophoblastic tumor ( GTT ) . STUDY DESIGN From 1985 to 2001 , 36 patients with World Health Organization (WHO)--defined high-risk GTT were treated with MEA or FA at Chiba University Hospital . Thirty-three patients were initially treated with MEA . FA was administered to 11 patients ; 1 had had no previous chemotherapy , 7 had developed drug resistance to MEA , 1 had relapsed following MEA , and 2 had relapsed following etoposide/methotrexate/actinomycin D/ cyclophosphamide/vincristine ( EMA/CO ) combination chemotherapy . RESULTS The primary remission rate with MEA was 69.7 % ( 23 of 33 ) . With FA the survival rate was 81.8 % ( 9 of 11 ) for a mean follow-up period of 11.5 years . Two patients died due to multidrug resistance , and 2 patients relapsed subsequently . The 2 relapse cases were successfully salvaged again with MEA . The toxicity of FA was evaluated in 89 cycles . Myelosuppression seemed to be the dose-limiting toxicity , and the incidence of WHO grade 4 leukocytopenia and thrombocytopenia were 5.6 % and 3.4 % , respectively . CONCLUSION Although etoposide-containing chemotherapy is currently the most effective and well tolerated regimen for high-risk GTT , 20 - 30 % of patients develop drug resistance to these regimens . Salvage combination chemotherapy with FA is effective for refractory patients , and the toxicity is predictable and manageable Multiple agent chemotherapy in high-risk metastatic gestational trophoblastic tumor patients is a problem for any medical team . In this study , EMA-EP chemotherapy ( etoposide , methotrexate , actinomycin , and cisplatinum ) was evaluated as firstline chemotherapy to manage high-risk GTT metastatic patients . Seventeen high-risk metastatic patients , including 14 without and 3 with brain metastasis , who were c and i date s to firstline multiple agent chemotherapy between April 2000 and March 2003 in Vali-e-Asr hospital took part in a prospect i ve study under EMA-EP regimen . EMA-EP was prescribed in two periods : EMA in two consecutive days in week 1 and EP in 1 day in the following week with a week interval between these two ( each cycle was repeated every 2 weeks ) . In brain metastasis group , patients got high-dose medication ( methotrexate ) together with brain radiotherapy . Remission , toxicity , full dose tolerance , and recurrences of patients were evaluated . Median age of patients was 30 ( 15–49 ) , and they received 100 courses of chemotherapy including 75 low-dose courses and 25 high-dose courses . 71 % of courses were done in full dosage ( 83 % in low dose and 36 % in high dose ) . The most common cause for dosage reduction was leukopenia . Two patients did not complete the regimen , one due to hypersensitivity and the other due to fever and leukopenia leading to death . All others , who received complete courses , achieved remission . In the group without brain metastasis , one case of recurrence was observed . Grade 3 anemia , grade 3 and 4 leukopenia , and grade 3 and 4 thrombocytopenia were observed in 3 , 12 , and 3 % of patients , respectively . In current study , EMA-EP regimen in patients with high-risk metastatic GTN patients ( with or without brain metastasis ) lead to remission in all patients who completed the treatment courses OBJECTIVE To evaluate the effectiveness of the etoposide and cisplatin/etoposide , methotrexate and actinomycin D ( EP-EMA ) regimen in patients with gestational trophoblastic neoplasia who had been successfully treated with the etoposide , methotrexate , and actinomycin D/cyclophosphamide and vincristine ( EMA-CO ) regimen but experienced a relapse , or who became refractory to EMA-CO treatment . METHODS From January 1999 to December 2005 , 18 patients with gestational trophoblastic neoplasia who had been successfully treated with the EMA-CO regimen but sustained a relapse ( n=7 ) or who became refractory to it ( n=11 ) were treated with the EP-EMA regimen . The effectiveness , adverse effects , and tolerated dose intensity of the EP-EMA regimen were retrospectively analyzed . RESULTS The 18 patients received a total of 74 cycles of the EP-EMA regimen and 12 ( 66.7 % ) achieved complete remission . Nine of the 11 patients ( 81.8 % ) apparently resistant to the EMA-CO regimen achieved complete remission . However , only 3 of the 7 patients ( 42.9 % ) who experienced a relapse after Output:	RCTs in GTN are scarce owing to the low prevalence of this disease and its highly chemosensitive nature . However , five-day dactinomycin is associated with more side effects than pulsed dactinomycin , therefore an RCT comparing the relative efficacy and safety of these two regimens in the context of failed primary methotrexate treatment is desirable .
MS22518	*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 determine whether a limited oxygen strategy ( LOX ) versus a high oxygen strategy ( HOX ) during delivery room resuscitation decreases oxidative stress in preterm neonates . METHODS : A r and omized trial of neonates of 24 to 34 weeks ’ gestational age ( GA ) who received resuscitation was performed . LOX neonates received room air as the initial resuscitation gas , and fraction of inspired oxygen ( Fio2 ) was adjusted by 10 % every 30 seconds to achieve target preductal oxygen saturations ( Spo2 ) as described by the 2010 Neonatal Resuscitation Program guidelines . HOX neonates received 100 % O2 as initial resuscitation gas , and Fio2 was adjusted by 10 % to keep preductal Spo2 at 85 % to 94 % . Total hydroperoxide ( TH ) , biological antioxidant potential ( BAP ) , and the oxidative balance ratio ( BAP/TH ) were analyzed in cord blood and the first hour of life . Secondary outcomes included delivery room interventions , respiratory support on NICU admission , and short-term morbidities . RESULTS : Forty-four LOX ( GA : 30 ± 3 weeks ; birth weight : 1678 ± 634 g ) and 44 HOX ( GA : 30 ± 3 weeks ; birth weight : 1463 ± 606 g ) neonates were included . LOX decreased integrated excess oxygen ( ∑Fio2 × time [ min ] ) in the delivery room compared with HOX ( 401 ± 151 vs 662 ± 249 ; P < .01 ) . At 1 hour of life , BAP/TH was 60 % higher for LOX versus HOX neonates ( 13 [ 9–16 ] vs 8 [ 6–9 ] ) µM/U.CARR , P < .01 ) . LOX decreased ventilator days ( 3 [ 0–64 ] vs 8 [ 0–96 ] ; P < .05 ) and reduced the incidence of bronchopulmonary dysplasia ( 7 % vs 25 % ; P < .05 ) . CONCLUSIONS : LOX is feasible and results in less oxygen exposure , lower oxidative stress , and decreased respiratory morbidities and thus is a reasonable alternative for resuscitation of preterm neonates in the delivery room OBJECTIVE : To determine if practice s related to the use of pulse oximetry in the first 2 weeks following birth and after 2 weeks of age have a relationship to the rate of retinopathy of prematurity ( ROP ) and retinal ablation surgery in infants ≤1500 g. STUDY DESIGN : A question naire was mailed in July 2001 to 318 neonatal intensive care units ( NICUs ) in the United States and information was collected regarding SpO2 guidelines and the rate of both severe ROP and retinal ablation surgery . RESULTS : A total of 142 surveys were returned ( 45 % ) . In all , 87 % of the NICUs had SpO2 guidelines , and 60 % of these centers maintained a different range of SpO2 for infants ≤ or > 2 weeks of age . The range of SpO2 was 82 to 100 % with an average minimum ( min ) and maximum ( max ) of 89 and 95 % , respectively . In the NICUs with an SpO2 max of > 98 % in the first 2 weeks following birth , the rate of retinal ablation surgery was 5.5 vs 3 % in those units with a max SpO2 > 98 % ( p<0.05 ) . After 2 weeks of age , the rate of retinal ablation surgery was 3.3 % when max SpO2 was > 92 vs 1.3 % when the max SpO2 was ≤92 % ( p<0.00001 ) . The rate of ≥stage 3 ROP after 2 weeks of age was 5.5 % when max SpO2 was > 92 vs 2.4 % when max SpO2 was ≤92 % ( p<0.0005 ) . CONCLUSION : NICUs in the US today have a wide range of SpO2 guidelines . The results of this survey show a “ gradient of risk ” towards less retinal ablation surgery when the max SpO2 is < 98 % in the first 2 weeks following birth ( p<0.05 ) . There was a statistically significant lower rate of ≥stage 3 ROP and retinal ablation surgery when the max SpO2 was ≤92 % after the first 2 weeks of age . A r and omized , controlled trial is needed to establish a safe upper limit of SpO2 in the premature infant at risk for developing ROP BACKGROUND Previous studies have suggested that the incidence of retinopathy is lower in preterm infants with exposure to reduced levels of oxygenation than in those exposed to higher levels of oxygenation . However , it is unclear what range of oxygen saturation is appropriate to minimize retinopathy without increasing adverse outcomes . METHODS We performed a r and omized trial with a 2-by-2 factorial design to compare target ranges of oxygen saturation of 85 to 89 % or 91 to 95 % among 1316 infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation . The primary outcome was a composite of severe retinopathy of prematurity ( defined as the presence of threshold retinopathy , the need for surgical ophthalmologic intervention , or the use of bevacizumab ) , death before discharge from the hospital , or both . All infants were also r and omly assigned to continuous positive airway pressure or intubation and surfactant . RESULTS The rates of severe retinopathy or death did not differ significantly between the lower-oxygen-saturation group and the higher-oxygen-saturation group ( 28.3 % and 32.1 % , respectively ; relative risk with lower oxygen saturation , 0.90 ; 95 % confidence interval [ CI ] , 0.76 to 1.06 ; P=0.21 ) . Death before discharge occurred more frequently in the lower-oxygen-saturation group ( in 19.9 % of infants vs. 16.2 % ; relative risk , 1.27 ; 95 % CI , 1.01 to 1.60 ; P=0.04 ) , whereas severe retinopathy among survivors occurred less often in this group ( 8.6 % vs. 17.9 % ; relative risk , 0.52 ; 95 % CI , 0.37 to 0.73 ; P<0.001 ) . There were no significant differences in the rates of other adverse events . CONCLUSIONS A lower target range of oxygenation ( 85 to 89 % ) , as compared with a higher range ( 91 to 95 % ) , did not significantly decrease the composite outcome of severe retinopathy or death , but it result ed in an increase in mortality and a substantial decrease in severe retinopathy among survivors . The increase in mortality is a major concern , since a lower target range of oxygen saturation is increasingly being advocated to prevent retinopathy of prematurity . ( Clinical Trials.gov number , NCT00233324 . OBJECTIVE : The goal was to reduce adverse pulmonary adverse outcomes , oxidative stress , and inflammation in neonates of 24 to 28 weeks of gestation initially resuscitated with fractions of inspired oxygen of 30 % or 90 % . METHODS : R and omized assignment to receive 30 % ( N = 37 ) or 90 % ( N = 41 ) oxygen was performed . Targeted oxygen saturation values were 75 % at 5 minutes and 85 % at 10 minutes . Blood oxidized glutathione (GSSG)/reduced glutathione ratio and urinary o-tyrosine , 8-oxo-dihydroxyguanosine , and isoprostane levels , isofuran elimination , and plasma interleukin 8 and tumor necrosis factor α levels were determined . RESULTS : The low-oxygen group needed fewer days of oxygen supplementation ( 6 vs 22 days ; P < .01 ) and fewer days of mechanical ventilation ( 13 vs 27 days ; P < .01 ) and had a lower incidence of bronchopulmonary dysplasia at discharge ( 15.4 % vs 31.7 % ; P < .05 ) . GSSG/reduced glutathione × 100 ratios at day 1 and 3 were significantly higher in the high-oxygen group ( day 1 : high-oxygen group : 13.36 ± 5.25 ; low-oxygen group : 8.46 ± 3.87 ; P < .01 ; day 3 : high-oxygen group : 8.87 ± 4.40 ; low-oxygen group : 6.97 ± 3.11 ; P < .05 ) . Urinary markers of oxidative stress were increased significantly in the high-oxygen group , compared with the low-oxygen group , in the first week after birth . GSSG levels on day 3 and urinary isofuran , o-tyrosine , and 8-hydroxy-2′-deoxyguanosine levels on day 7 were correlated significantly with development of chronic lung disease . CONCLUSIONS : Resuscitation of preterm neonates with 30 % oxygen causes less oxidative stress , inflammation , need for oxygen , and risk of bronchopulmonary dysplasia OBJECTIVE To assess whether an oxygen saturation ( Spo2 ) target of 85%-89 % compared with 91%-95 % reduced the incidence of the composite outcome of death or major disability at 2 years of age in infants born at < 28 weeks ' gestation . STUDY DESIGN A total 340 infants were r and omized to a lower or higher target from < 24 hours of age until 36 weeks ' gestational age . Blinding was achieved by targeting a displayed Spo2 of 88%-92 % using a saturation monitor offset by ±3 % within the range 85%-95 % . True saturations were displayed outside this range . Follow-up at 2 years ' corrected age was by pediatric examination and formal neurodevelopmental assessment . Major disability was gross motor disability , cognitive or language delay , severe hearing loss , or blindness . RESULTS The primary outcome was known for 335 infants with 33 using surrogate language information . Targeting a lower compared with a higher Spo2 target range had no significant effect on the rate of death or major disability at 2 years ' corrected age ( 65/167 [ 38.9 % ] vs 76/168 [ 45.2 % ] ; relative risk 1.15 , 95 % CI 0.90 - 1.47 ) or any secondary outcomes . Death occurred in 25 ( 14.7 % ) and 27 ( 15.9 % ) of those r and omized to the lower and higher target , respectively , and blindness in 0 % and 0.7 % . CONCLUSIONS Although there was no benefit or harm from targeting a lower compared with a higher saturation in this trial , further information will become available from the prospect ively planned meta- analysis of this and 4 other trials comprising a total of nearly 5000 infants The relation between PaO2 and retrolental fibroplasia ( RLF ) was studied prospect ively in 719 premature infants born in or treated in the intensive care units of a group of university hospitals . Blood gas studies were performed on 589 of these infants , 66 of whom had a diagnosis of RLF ; in 27 of these 66 , some grade of mostly nonblinding cicatricial disease developed . The frequency of RLF was highest among infants of lowest birth weight . A multivariate statistical method was used to analyze simultaneously the effect of possible etiologic factors associated with RLF . The occurrence of RLF was found to be unrelated to PaO2 , as determined by the limited information available from intermittent sampling . RLF is associated with concentration of oxygen administered in the lightest birth weight group , but the strongest association , aside from birth weight , was with time in oxygen . None of the other variables involving blood chemical values appeared to be associated with RLF . The severity of cicatricial RLF is clearly greater in infants weighing less than 1,200 g at birth . Conservative administration of oxygen may have been responsible for failure to demonstrate quantitative association between PaO2 levels and disease . Agreement between the observed and predicted numbers of infants with RLF demonstrate the strength of the multivariate technique employed in making the statistical analyses AIMS : To determine if decreasing arterial blood saturation from 95 % to 90 % could cause vasoconstriction of the pulmonary vasculature and dilatation of a patent ductus arteriosus in preterm newborn infants with respiratory distress syndrome ( RDS ) . METHODS : Doppler echocardiographic studies were compared at 95 % and 90 % pulse oxygen saturation ( SpO2 ) in 13 preterm infants aged 61.7 ( 4.3 ) hours with RDS and Doppler echocardiographic evidence of tricuspid regurgitation . RESULTS : The mean (SD)Doppler echocardiographic indices determined at 95 % were heart rate ( 146 ( 3.60 ) beats per minute ) , acceleration time of the velocity wave forms of the pulmonary artery ( PAAT ) ( 51.8 ( 2.5 ) milliseconds ) , ratio of PAAT to right ventricular ejection time ( ET ) ( Output:	In extremely preterm infants , targeting lower ( 85 % to 89 % ) SpO₂ compared to higher ( 91 % to 95 % ) SpO₂ had no significant effect on the composite outcome of death or major disability or on major disability alone , including blindness , but increased the average risk of mortality by 28 per 1000 infants treated .
MS22519	*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 Prospect i ve studies indicate that baseline levels of C-reactive protein ( CRP ) , the prototypic marker of inflammation , are associated with an increased risk for cardiovascular events . Limited studies have examined therapies that influence high-sensitive CRP ( hs-CRP ) levels , especially in hyperlipidemic patients . Thus , we tested the effects of 3 hydroxymethyl glutaryl coenzyme A reductase inhibitors ( statins ) , simvastatin ( 20 mg/d ) , pravastatin ( 40 mg/d ) , and atorvastatin ( 10 mg/d ) , on levels of hs-CRP in a r and omized , double-blind , crossover trial of 22 patients with combined hyperlipidemia ( LDL cholesterol > 130 mg/dL and triglycerides of 200 to 600 mg/dL ) . Methods and Results After 6 weeks of an American Heart Association Step 1 diet , fasting blood sample s were drawn at baseline and after 6 weeks of therapy with each drug . hs-CRP levels were significantly decreased after treatment with all 3 statins compared with baseline ( median values : baseline , 2.6 mg/L ; atorvastatin , 1.7 mg/L ; simvastatin , 1.7 mg/L ; and pravastatin , 1.9 mg/L;P < 0.025 ) . The reductions obtained with the 3 statins were similar . In addition , there was no significant effect on either plasma interleukin-6 or interleukin-6 soluble receptor levels . There was no relationship between reductions in hs-CRP and LDL cholesterol . Conclusions Pravastatin , simvastatin , and atorvastatin significantly decreased levels of hs-CRP . These data support an anti-inflammatory effect of these drugs Our objective was to examine the influence of various demographic , clinical , and enrollment biochemical variables on the long-term survival of continuous ambulatory peritoneal dialysis ( CAPD ) patients . This was a prospect i ve cohort study investigating the relationship between demographics and enrollment biochemical markers and mortality in CAPD patients in a CAPD unit in a large tertiary care teaching hospital . One hundred and sixtynine patients in the CAPD program were enrolled between 1989 and 1994 , and were followed up to 60 months . Independent predictors of mortality determined by Cox proportional hazards model included age , diabetes , serum albumin and creatinine . Enrollment level of serum albumin , and creatinine can predict mortality in CAPD patients up to 60 months . Markers of visceral and somatic nutrition at enrollment are important predictors of mortality in CAPD patients up to five years Statins are first-line pharmacotherapeutic agents for hypercholesterolemia treatment in humans . However the effects of statins in animal models of atherosclerosis are not very consistent . Thus we wanted to evaluate whether atorvastatin possesses hypolipidemic and anti-inflammatory effects in mice lacking apolipoprotein E/low-density lipoprotein receptor ( apoE/LDLR-deficient mice ) . Two-month-old female apoE/LDLR-deficient mice ( n=24 ) were r and omly subdivided into 3 groups . The control group of animals ( n=8 ) was fed with the western type diet ( atherogenic diet ) and in other two groups atorvastatin was added to the atherogenic diet at the dosage of either 10 mg/kg or 100 mg/kg per day for a period of 2 months . Biochemical analysis of lipids , ELISA analysis of monocyte chemotactic protein-1 ( MCP-1 ) in blood , quantification of lesion size and expression of vascular cell adhesion molecule-1 ( VCAM-1 ) and intercellular cell adhesion molecule-1 ( ICAM-1 ) in the atherosclerotic lesion by means of immunohistochemistry and Western blot analysis were performed . The biochemical analysis showed that administration of atorvastatin ( 100 mg/kg/day ) significantly decreased level of total cholesterol , lipoproteins ( VLDL and LDL ) , triacylglycerol , and moreover significantly increased level of HDL . ELISA analysis showed that atorvastatin significantly decreased levels of MCP-1 in blood and immunohistochemical and Western blot analysis showed significant reduction of VCAM-1 and ICAM-1 expression in the vessel wall after atorvastatin treatment ( 100 mg/kg/day ) . In conclusion , we demonstrated here for the first time strong hypolipidemic and anti-inflammatory effects of atorvastatin in apoE/LDLR-deficient mice . Thus , we propose that apoE/LDLR-deficient mice might be a good animal model for the study of statin effects on potential novel markers involved in atherogenesis and for the testing of potential combination treatment of new hypolipidemic substances with statins BACKGROUND Atherosclerosis , a major problem in patients on chronic hemodialysis , has been characterized as an inflammatory disease . C-reactive protein ( CRP ) , the prototypical acute phase protein in humans , is a predictor of cardiovascular mortality in the general population . We hypothesize that several of the classic , as well as nontraditional , cardiovascular risk factors may respond to acute phase reactions . An activated acute phase response may influence or predict cardiovascular risk . METHODS In 280 stable hemodialysis patients , serum lipids , apolipoproteins ( apo ) A-I and B , lipoprotein(a ) [ Lp(a ) ] , fibrinogen , and serum albumin ( Salb ) were determined in relation to CRP and serum amyloid A ( SAA ) , two sensitive markers of an acute phase response . Mortality was monitored prospect ively over a two year period . RESULTS Serum CRP and SAA were found to be elevated ( more than 8 and more than 10 mg/liter , respectively ) in 46 % and 47 % of the patients in the absence of clinical ly apparent infection . Patients with elevated CRP or SAA had significantly higher serum levels of Lp(a ) , higher plasma fibrinogen , and lower serum levels of high-density lipoprotein cholesterol , apo A-I , and Salb than patients with normal CRP or SAA . The rise in Lp(a ) concentration was restricted to patients exhibiting high molecular weight apo(a ) isoforms . During follow-up , 72 patients ( 25.7 % ) had died , mostly due to cardiovascular events ( 58 % ) . Overall mortality and cardiovascular mortality were significantly higher in patients with elevated CRP ( 31 % vs. 16 % , P < 0.0001 , and 23 % vs. 5 % , P < 0.0001 , respectively ) or SAA ( 29 % vs. 19 % , P = 0.004 , and 20 vs. 10 % , P = 0.008 , respectively ) and were also higher in patients with Salb of lower than 40 g/liter ( 44 % vs. 14 % , P < 0.0001 , and 34 % vs. 6 % , P < 0.0001 , respectively ) . Univariate Cox regression analysis demonstrated that age , diabetes , pre-existing cardiovascular disease , body mass index , CRP , SAA , Salb , fibrinogen , apo A-I , and Lp(a ) were significantly associated with the risk of all-cause and cardiovascular mortality . During multivariate regression analysis , SAA , fibrinogen , apo A-I , and Lp(a ) lost their predictive values , but age and CRP remained powerful independent predictors of both overall death and cardiovascular death . CONCLUSION These results suggest that a considerable number of hemodialysis patients exhibit an activated acute phase response , which is closely related to high levels of atherogenic vascular risk factors and cardiovascular death . The mechanisms of activated acute phase reaction in patients on chronic hemodialysis remain to be identified . A successful treatment of the inflammatory condition may improve long-term survival in these patients BACKGROUND Arterial stiffness assessed by pulse wave velocity ( PWV ) predicts all-cause and cardiovascular mortality in diabetic patients with end-stage renal disease . We studied the preventive effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor , fluvastatin , on arterial PWV values in this population . METHODS Twenty-two patients with normal serum lipid levels received fluvastatin ( 20 mg/day p.o . ) or a placebo for 6 months . Their serum lipid levels , serum levels of C-reactive protein ( CRP ) , arterial PWV , and ankle brachial indexes ( ABI ) were determined before , and 3 and 6 months after taking the medication to evaluate arterial stiffness . RESULTS At the beginning of the follow-up , there were no differences in age , blood pressure , body mass index , serum haemoglobin A1c level , serum CRP level , serum lipid levels , PWV or ABI between the placebo- ( n=10 ) and the fluvastatin-treated patients ( n=12 ) . After 6 months , the PWV and the serum oxidized low-density lipoprotein cholesterol ( LDL-C ) level increased significantly ( from 1969+/-140 to 2326+/-190 cm/s and 70.4+/-13.8 to 91.8+/-15.5 U/l , respectively ) in the placebo-treated patients . However , the fluvastatin group had a significantly reduced PWV ( from 1991+/-162 to 1709+/-134 cm/s ) , oxidized LDL-C serum levels ( from 89.0+/-9.6 to 73.0+/-5.8 U/l ) and CRP serum levels ( from 0.97+/-0.32 to 0.26+/-0.16 mg/dl ) compared with those in the placebo group . CONCLUSIONS Long-term administration of fluvastatin prevents further worsening of arterial biomechanics in haemodialysis patients with type 2 diabetes mellitus , even in the presence of serum lipid levels in the normal range BACKGROUND Cardiovascular disease is the most common cause of mortality in patients with end-stage renal disease . Cardiovascular benefits of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) have been clearly established in the general population , but not in dialysis patients . This study examined statin prescription patterns and assessed the relationship between statin prescription and clinical outcomes in hemodialysis ( HD ) patients . METHODS Data were analyzed from the Dialysis Outcomes and Practice Patterns Study , a prospect i ve observational study of HD patients r and omly selected from representative dialysis facilities in France , Germany , Italy , Spain , the United Kingdom , Japan , and the United States . Predictors of statin prescription were investigated by means of logistic regression . Cox regression models tested the association between statin prescription and risk for mortality and cardiac events , with adjustments for common demographic factors and comorbid conditions . RESULTS Statins were prescribed for 11.8 % of HD patients overall . Most facilities ( 81.2 % ) prescribed statins to less than 20 % of their patients . Patients prescribed statins had a 31 % lower relative risk for death compared with those not prescribed statins ( P < 0.0001 ) . Statins were associated with a 23 % lower cardiac mortality risk ( P = 0.03 ) and a 44 % lower noncardiac mortality risk ( P < 0.0001 ) . At a facility level , prescribing statins was associated with lower overall mortality rate , with a 5 % lower risk for every 10 % increase in number of patients prescribed statins within the facility ( P = 0.02 ) . CONCLUSION Statin prescription is associated with reduced mortality in HD patients , providing additional support for the value of statin therapy in this patient group Background : Dialysis patients have many underlying traditional and nontraditional risk factors that may predispose them to a high prevalence of cardiovascular disease . The effects of statins ( eg , atorvastatin ) on altering nontraditional lipoprotein measures in dialysis patients have not been extensively investigated . Objective : To evaluate the efficacy of atorvastatin compared with a control group in inducing changes in lipoprotein(a ) [ Lp(a ) ] , apolipoprotein ( Apo ) A-1 , Apo-B , and fibrinogen levels , as well as the conventional lipoprotein profile , in hemodialysis patients over 36 weeks ; secondary objectives were to assess changes in C-reactive protein , albumin , and safety measures . Methods : Forty-five hemodialysis patients with low-density lipoprotein cholesterol ( LDL-C ) levels greater than 100 mg/dL were r and omized to parallel groups : atorvastatin ( n = 19 ) or no treatment ( n = 26 ) . The atorvastatin dose was titrated from 10 mg to achieve an LDL-C goal of 100 mg/dL or less and therapy was continued for 36 weeks . Biochemical and lipoprotein laboratory tests for efficacy outcomes were obtained at baseline , 12 weeks , and 36 weeks . Results : The atorvastatin group exhibited clinical ly significant reductions ( Output:	CONCLUSIONS Statins can improve the chronic inflammation status reflected by the decreasing of serum CRP and hs-CRP levels , whereas there is no conclusive evidence that it can improve the nutrition status .
MS22520	*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 : Mild therapeutic hypothermia after out-of-hospital cardiac arrest is usually achieved either by surface cooling or by core cooling via the patient 's bloodstream . We compared modern core ( Coolgard ) and surface ( A rct ic Sun ) cooling devices with a zero hypothesis of equal cooling , complications , and neurologic outcomes . Design : Single-center observational study . Setting : University hospital medical and cardiac intensive care units . Patients : One hundred sixty-seven consecutive patients comatose after out-of-hospital cardiac arrest of all causes treated with mild therapeutic hypothermia in a 5-yr period . Interventions : Nonr and omized allocation to core or surface cooling depending on availability and physician preference . Measurements and Main Results : All out-of-hospital cardiac arrest patients ' records were review ed for relevant data regarding medical history , cardiac arrest event , prehospital care , in-hospital treatment , and complications . Survivor neurologic function was reassessed at follow-up after 6 to 12 months . Baseline patient and arrest episode characteristics were similar in the treatment groups . There was no significant difference in survival with good neurologic function , either to hospital discharge ( surface , 34/90 , 38 % ; core , 34/75 , 45 % ; p = .345 ) or at follow-up ( surface , 34/88 , 39 % ; core , 34/75 , 45 % ; p = .387 ) . Time from cardiac arrest to achieving mild therapeutic hypothermia was equal with both devices ( surface , 273 min , interquartile range 158–330 ; core , 270 min , interquartile range 190–360 ; p = .479 ) . There were significantly more episodes of sustained hyperglycemia among the surface-cooled patients ( surface , 64/92 , 70 % ; core , 36/75 , 48 % ; p = .005 ) and significantly more hypomagnesaemia among core-cooled patients ( surface , 16/87 , 18 % ; core , 27/74 , 37 % ; p = .01 ) . Conclusions : In this study , surface and core cooling of out-of-hospital cardiac arrest patients following the same established postresuscitation treatment protocol result ed in similar survival to hospital discharge and comparable neurologic function at follow-up Introduction Mild induced hypothermia ( MIH ) is indicated for comatose survivors of sudden cardiac arrest ( SCA ) to improve clinical outcome . In this study , we compared the efficacy of two different cooling devices for temperature management in SCA survivors . Methods Between April 2008 and August 2009 , 80 patients after survived in-hospital ( IHCA ) and out-of-hospital cardiac arrest ( OHCA ) were included in this prospect i ve , r and omized , single center study . Hypothermia was induced after r and omization by either invasive Coolgard ® cooling or non-invasive A rct icSun ® surface cooling at 33.0 ° C core body temperature for 24 h followed by active rewarming . The primary endpoint was defined as the efficacy of both cooling systems , measured by neuron-specific enolase ( NSE ) levels as a surrogate parameter for brain damage . Secondary efficacy endpoints were the clinical and neurological outcome , time to start of cooling and reaching the target temperature , target temperature-maintenance and hypothermia-associated complications . Results NSE at 72 h did not differ significantly between the 2 groups with 16.5 ng/ml , interquartile range 11.8–46.5 in surface-cooled patients versus 19.0 ng/ml , interquartile range 11.0–42.0 in invasive-cooled patients , p = 0.99 . Neurological and clinical outcome was similar in both groups . Target temperature of 33.0 ° C was maintained more stable in the invasive group ( 33.0 versus 32.7 ° C , p < 0.001 ) . Bleeding complications were more frequent with invasive cooling ( n = 17 [ 43.6 % ] versus n = 7 [ 17.9 % ] ; p = 0.03 ) . Conclusion Invasive cooling has advantages with respect to temperature management over surface cooling ; however , did not result in different outcome as measured by NSE release in SCA survivors . Bleeding complications were more frequently encountered by invasive cooling BACKGROUND Therapeutic hypothermia is currently the best-documented method of improving neurological outcomes in patients after cardiac arrest and successful resuscitation . There is a variety of methods for lowering body temperature . However , there are no data showing that any specific method of cooling improves the results or increases survival . A simple method involving surface cooling and ice-cold intravenous fluids , as well as more technologically advanced methods , are used in clinical practice . One of the more advanced methods is intravascular hypothermia , during which cooling is carried out with the use of a special catheter located in the central vein . AIM To compare cooling with the use of intravascular hypothermia and cooling using the traditional method . METHODS A prospect i ve study was performed in 41 patients with acute coronary syndromes who did not regain consciousness after out-of-hospital or in-hospital cardiac arrest and restoration of spontaneous circulation . Therapeutic hypothermia ( 32 - 34 ° C ) was obtained with the use of an intravascular method ( group A , n = 20 ) or a traditional method ( group B , n = 21 ) for a period of 24 hours . Intravascular cooling involved the use of a catheter inserted in the femoral vein connected to a heat exchanger ( Alsius Coolgard , Zoll , Chelmsford , MA , USA ) . Traditional cooling was carried out using uncontrolled surface cooling , ice-cold intravenous fluids and ice-cold gastric lavage . Nasopharyngeal and urinary bladder temperatures were recorded hourly . The main analysed temperature was the urinary bladder temperature , as the heat exchanger in the intravascular hypothermia group was controlled by the readings taken from this site . Temperature profiles were compared . RESULTS Temperature < 34 ° C was reached in 19 ( 95.0 % ) patients in group A and in 11 ( 52.4 % ) patients in group B ( p = 0.004 ) . Stable temperature profile ( temperature in the range 32 - 34 ° C during the final 12 h of cooling ) was reached in 16 ( 80 % ) patients in group A and in three ( 14.3 % ) patients in group B ( p < 0.001 ) . Periods of inadequate cooling ( temperature > 34 ° C ) and temperature overshoots ( temperature < 32 ° C ) were significantly more frequent in group B. Temperature profiles were significantly different in both groups in the readings taken from both sites . CONCLUSIONS The presented technique of intravascular hypothermia provides more precise temperature control in comparison with the traditional method BACKGROUND Mild therapeutic hypothermia ( 32 - 36 ° C ) is associated with improved outcomes in patients with brain injury after cardiac arrest ( CA ) . Various devices are available to induce and maintain hypothermia , but few studies have compared the performance of these devices . We performed a prospect i ve study to compare four frequently used cooling systems in inducing and maintaining hypothermia followed by controlled rewarming . METHODS We performed a prospect i ve multi-centered study in ten ICU 's in three hospitals within the UPMC health system . Four different cooling technologies ( seven cooling methods in total ) were studied : two external water-circulating cooling blankets ( Meditherm ® and Blanketrol ® ) , gel-coated adhesive cooling pads ( A rct ic Sun ® ) , and endovascular cooling catheters with balloons circulating ice-cold saline ( Thermogard ® ) . For the latter system we studied three different types of catheter with two , three or four water-circulating balloons , respectively . In contrast to previous studies , we not only studied the cooling rate ( i.e. , time to target temperature ) in the induction phase , but also the percentage of the time during the maintenance phase that temperature was on target ±0.5 ° C , and the efficacy of devices to control rewarming . We believe that these are more important indicators of device performance than induction speed alone . RESULTS 129 consecutive patients admitted after CA and treated with hypothermia were screened , and 120 were enrolled in the study . Two research ers dedicated fulltime to this study monitored TH treatment in all patients , including antishivering measures , additional cooling measures used ( e.g. icepacks and cold fluid infusion ) , and all other issues related to temperature management . Baseline characteristics were similar for all groups . Cooling rates were 2.06 ± 1.12 ° C/h for endovascular cooling , 1.49 ± 0.82 for A rct ic sun , 0.61 ± 0.36 for Meditherm and 1.22 ± 1.12 for Blanketrol . Time within target range ±0.5 ° C was 97.3 ± 6.0 % for Thermogard , 81.8 ± 25.2 % for A rct ic Sun , 57.4 ± 29.3 % for Meditherm , and 64.5 ± 20.1 % for Blanketrol . The following differences were significant : Thermogard vs. Meditherm ( p < 0.01 ) , Thermogard vs. Blanketrol ( p < 0.01 ) , and A rct ic Sun vs. Meditherm ( p < 0.02 ) . No major complications occurred with any device . CONCLUSIONS Endovascular cooling and gel-adhesive pads provide more rapid hypothermia induction and more effective temperature maintenance compared to water-circulating cooling blankets . This applied to induction speed , but ( more importantly ) also to time within target range during maintenance Background and Purpose — Recently 2 r and omized trials in comatose survivors of cardiac arrest documented that therapeutic hypothermia improved neurological recovery . The narrow inclusion criteria result ed in an international recommendation to cool only a restricted group of primary cardiac arrest survivors . In this retrospective cohort study we investigated the efficacy and safety of endovascular cooling in unselected survivors of cardiac arrest . Methods — Consecutive comatose survivors of cardiac arrest , who were either cooled for 24 hours to 33 ° C with endovascular cooling or treated with st and ard postresuscitation therapy , were analyzed . Complication data were obtained by retrospective chart review . Results — Patients in the endovascular cooling group had 2-fold increased odds of survival ( 67/97 patients versus 466/941 patients ; odds ratio 2.28 , 95 % CI , 1.45 to 3.57 ; P<0.001 ) . After adjustment for baseline imbalances the odds ratio was 1.96 ( 95 % CI , 1.19 to 3.23 ; P=0.008 ) . When discounting the observational data in a Bayesian analysis by using a sceptical prior the posterior odds ratio was 1.61 ( 95 % credible interval , 1.06 to 2.44 ) . In the endovascular cooling group , 51/97 patients ( 53 % ) survived with favorable neurology as compared with 320/941 ( 34 % ) in the control group ( odds ratio 2.15 , 95 % CI , 1.38 to 3.35 ; P=0.0003 ; adjusted odds ratio 2.56 , 1.57 to 4.17 ) . There was no difference in the rate of complications except for bradycardia . Conclusion — Endovascular cooling improved survival and short-term neurological recovery compared with st and ard treatment in comatose adult survivors of cardiac arrest . Temperature control was effective and safe with this device BACKGROUND Cardiac arrest with widespread cerebral ischemia frequently leads to severe neurologic impairment . We studied whether mild systemic hypothermia increases the rate of neurologic recovery after resuscitation from cardiac arrest due to ventricular fibrillation . METHODS In this multicenter trial with blinded assessment of the outcome , patients who had been resuscitated after cardiac arrest due to ventricular fibrillation were r and omly assigned to undergo therapeutic hypothermia ( target temperature , 32 degrees C to 34 degrees C , measured in the bladder ) over a period of 24 hours or to receive st and ard treatment with normothermia . The primary end point was a favorable neurologic outcome within six months after cardiac arrest ; secondary end points were mortality within six months and the rate of complications within seven days . RESULTS Seventy-five of the 136 patients in the hypothermia group for whom data were available ( 55 percent ) had a favorable neurologic outcome ( cerebral-performance category , 1 [ good recovery ] or 2 [ moderate disability ] ) , as compared with 54 of 137 ( 39 percent ) in the normothermia group ( risk ratio , 1.40 ; 95 percent confidence interval , 1.08 to 1.81 ) . Mortality at six months was 41 percent in the hypothermia group ( 56 of 137 patients died ) , as compared with 55 percent in the normothermia group ( 76 of 138 patients ; risk ratio , 0.74 ; 95 percent confidence interval , 0.58 to 0.95 ) . The comp Output:	Among adult patients receiving cardiopulmonary resuscitation , although there is no significant difference between the two cooling methods in the time from the start of cardiac arrest to achieve the target temperature , the faster cooling rate and more stable cooling process in EC shorten patients ’ ICU hospitalization time and help more patients obtain good neurological prognosis compared with patients receiving SC . Meanwhile , although EC has no significant difference in patient outcomes compared with A rct icSun , EC has improved rates of neurologically intact survival
MS22521	*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 fecal microbiota is a rich source of biomarkers that have previously been shown to be predictive of numerous disease states . Less well studied is the effect of immunomodulatory therapy on the microbiota and its role in response to therapy . This study explored associations between the fecal microbiota and therapeutic response of Crohn ’s disease ( CD ) patients treated with ustekinumab ( UST ; Stelara ) in the phase 2 CERTIFI study . Using stool sample s collected over the course of 22 weeks , the composition of these subjects ’ fecal bacterial communities was characterized by sequencing the 16S rRNA gene . Subjects in remission could be distinguished from those with active disease 6 weeks after treatment using r and om forest models trained on subjects ’ baseline microbiota and clinical data ( area under the curve [ AUC ] of 0.844 , specificity of 0.831 , sensitivity of 0.774 ) . The most predictive operational taxonomic units ( OTUs ) that were ubiquitous among subjects were affiliated with Faecalibacterium and Escherichia or Shigella . The median baseline community diversity in subjects in remission 6 weeks after treatment was 1.7 times higher than that in treated subjects with active disease ( P = 0.020 ) . Their baseline community structures were also significantly different ( P = 0.017 ) . Two OTUs affiliated with Faecalibacterium ( P = 0.003 ) and Bacteroides ( P = 0.022 ) were significantly more abundant at baseline in subjects who were in remission 6 weeks after treatment than those with active CD . The microbiota diversity of UST-treated clinical responders increased over the 22 weeks of the study , in contrast to nonresponsive subjects ( P = 0.012 ) . The observed baseline differences in fecal microbiota and changes due to therapeutic response support the potential for the microbiota as a response biomarker . IMPORTANCE CD is a global health concern , with increasing incidence and prevalence , causing large economic and health care impacts . Finding prognostic biomarkers that give clinicians the ability to identify patients more likely to respond to CD treatment at diagnosis will reduce the time subjects receive drugs that are unlikely to be beneficial . OTUs associated with remission after treatment induction , especially Faecalibacterium , could be biomarkers for successful UST treatment of anti-tumor necrosis factor alpha ( anti-TNF-α ) refractory CD patients . More broadly , these results suggest that the fecal microbiota could be a useful noninvasive biomarker for directing or monitoring the treatment of gastrointestinal diseases . IMPORTANCE CD is a global health concern , with increasing incidence and prevalence , causing large economic and health care impacts . Finding prognostic biomarkers that give clinicians the ability to identify patients more likely to respond to CD treatment at diagnosis will reduce the time subjects receive drugs that are unlikely to be beneficial . OTUs associated with remission after treatment induction , especially Faecalibacterium , could be biomarkers for successful UST treatment of anti-tumor necrosis factor alpha ( anti-TNF-α ) refractory CD patients . More broadly , these results suggest that the fecal microbiota could be a useful noninvasive biomarker for directing or monitoring the treatment of gastrointestinal diseases Background : Multiple sclerosis has an extremely variable natural course . In most patients , disease starts with a relapsing-remitting ( RR ) phase , which proceeds to a secondary progressive ( SP ) form . The duration of the RR phase is hard to predict , and to date predictions on the rate of disease progression remain suboptimal . This limits the opportunity to tailor therapy on an individual patient 's prognosis , in spite of the choice of several therapeutic options . Approaches to improve clinical decisions , such as collective intelligence of human groups and machine learning algorithms are widely investigated . Methods : Medical students and a machine learning algorithm predicted the course of disease on the basis of r and omly chosen clinical records of patients that attended at the Multiple Sclerosis service of Sant ' And rea hospital in Rome . Results : A significant improvement of predictive ability was obtained when predictions were combined with a weight that depends on the consistence of human ( or algorithm ) forecasts on a given clinical record . Conclusions : In this work we present proof-of-principle that human-machine hybrid predictions yield better prognoses than machine learning algorithms or groups of humans alone . To strengthen this preliminary result , we propose a crowdsourcing initiative to collect prognoses by physicians on an exp and ed set of patients BACKGROUND AND AIM Knowledge of long-term outcomes following an index episode of acute severe colitis ( ASC ) can help informed decision making at a time of acute exacerbation especially when colectomy is an option . We aim ed to identify long-term outcomes and their predictors after a first episode of ASC in a large North Indian cohort . METHODS Hospitalized patients satisfying Truelove and Witts ' criteria under follow-up at a single center from January 2003 to December 2013 were included . Patients avoiding colectomy at index admission were categorized as complete ( ≤ 3 non bloody stool per day ) or incomplete responders , based upon response to corticosteroids at day 7 . R and om Forest-based machine learning models were constructed to predict the long-term risk of colectomy or steroid dependence following an index episode of ASC . RESULTS Of 1731 patients with ulcerative colitis , 179 ( 10 % ) had an index episode of ASC . Nineteen ( 11 % ) patients underwent colectomy at index admission and 42 ( 26 % ) over a median follow-up of 56 ( 1 - 159 ) months . Hazard ratio for colectomy for incomplete responder was 3.6 ( 1.7 - 7.5 , P = 0.001 ) compared with complete responder . Modeling based on four variables , response at day 7 of hospitalization , steroid use during the first year of diagnosis , longer disease duration before ASC , and number of extra-intestinal manifestations , was able to predict colectomy with an accuracy of 77 % . CONCLUSIONS Disease behavior of ASC in India is similar to the West , with a third undergoing colectomy at 10 years . Clinical features , especially response at day 7 hospitalization for index ASC , can predict both colectomy and steroid dependence with reasonable accuracy Background : In type 1 diabetes mellitus ( T1DM ) , patients play an active role in their own care and need to have the knowledge to adapt decisions to their daily living conditions . Artificial intelligence applications can help people with type 1 diabetes in decision making and allow them to react at time scales shorter than the scheduled face-to-face visits . This work presents a decision support system ( DSS ) , based on glucose prediction , to assist patients in a mobile environment . Methods : The system ’s impact on therapeutic corrective actions has been evaluated in a r and omized crossover pilot study focused on interpr and ial periods . Twelve people with type 1 diabetes treated with insulin pump participated in two phases : In the experimental phase ( EP ) patients used the DSS to modify initial corrective decisions in presence of hypoglycemia or hyperglycemia events . In the control phase ( CP ) patients were asked to follow decisions without knowing the glucose prediction . A telemedicine platform allowed participants to register monitoring data and decisions and allowed endocrinologists to supervise data at the hospital . The study period was defined as a postprediction ( PP ) time window . Results : After knowing the glucose prediction , participants modified the initial decision in 20 % of the situations . No statistically significant differences were found in the PP Kovatchev ’s risk index change ( –1.23 ± 11.85 in EP vs –0.56 ± 6.06 in CP ) . Participants had a positive opinion about the DSS with an average score higher than 7 in a usability question naire . Conclusion : The DSS had a relevant impact in the participants ’ decision making while dealing with T1DM and showed a high confidence of patients in the use of glucose prediction Background and Aims Big data analytics leverage patterns in data to harvest valuable information , but are rarely implemented in clinical care . Optimising thiopurine therapy for inflammatory bowel disease [ IBD ] has proved difficult . Current methods using 6-thioguanine nucleotide [ 6-TGN ] metabolites have failed in r and omized controlled trials [ RCTs ] , and have not been used to predict objective remission [ OR ] . Our aims were to : 1 ) develop machine learning algorithms [ MLA ] using laboratory values and age to identify patients in objective remission on thiopurines ; and 2 ) determine whether achieving algorithm-predicted objective remission result ed in fewer clinical events per year . Methods Objective remission was defined as the absence of objective evidence of intestinal inflammation . MLAs were developed to predict three outcomes : objective remission , non-adherence , and preferential shunting to 6-methylmercaptopurine [ 6-MMP ] . The performance of the algorithms was evaluated using the area under the receiver operating characteristic curve [ AuROC ] . Clinical event rates of new steroid prescriptions , hospitalisations , and abdominal surgeries were measured . Results Retrospective review was performed on medical records of 1080 IBD patients on thiopurines . The AuROC for algorithm-predicted remission in the validation set was 0.79 vs 0.49 for 6-TGN . The mean number of clinical events per year in patients with sustained algorithm-predicted remission [ APR ] was 1.08 vs 3.95 in those that did not have sustained APR [ p < 1 x 10 - 5 ] . Reductions in the individual endpoints of steroid prescriptions/year [ -1.63 , p < 1 x 10 - 5 ] , hospitalisations/year [ -1.05 , p < 1 x 10 - 5 ] , and surgeries/year [ -0.19 , p = 0.065 ] were seen with algorithm-predicted remission . Conclusions A machine learning algorithm was able to identify IBD patients on thiopurines with algorithm-predicted objective remission , a state associated with significant clinical benefits , including decreased steroid prescriptions , hospitalisations , and surgeries Primary sclerosing cholangitis ( PSC ) is a liver disease known for its frequent concurrence with inflammatory bowel disease . Dysbiosis of the gut microbiota in PSC was reported in several studies , but the microbiological features of the salivary microbiota in PSC have not been established . Here we compared the salivary microbial communities of 24 pediatric-onset PSC patients , 16 age-matched ulcerative colitis ( UC ) patients , and 24 healthy controls ( HCs ) by analyzing the bacterial 16S rRNA gene sequence data . The species-richness ( α-diversity ) showed no significant between-group differences , whereas the overall salivary microbiota structure ( β-diversity ) showed significant differences among the three groups . Taxonomic assignment revealed that the PSC salivary microbiota were characterized by significant decreases in the abundance of Rothia and Haemophilus compared to the HC group , and significantly decreased Haemophilus and increased Oribacterium compared to the UC group . By combining the genera selected by the r and om forest algorithm in machine learning , followed by confirmation with 10-fold cross-validation , we were able to distinguish the PSC group from the HC group with the area under the curve ( AUC ) of 0.7423 , and from the UC group with the AUC of 0.8756 . Our results indicate the potential of salivary microbiota as biomarkers for a noninvasive diagnosis of PSC Background Identifying patients with certain clinical criteria based on manual chart review of doctors ’ notes is a daunting task given the massive amounts of text notes in the electronic health records ( EHR ) . This task can be automated using text classifiers based on Natural Language Processing ( NLP ) techniques along with pattern recognition machine learning ( ML ) algorithms . The aim of this research is to evaluate the performance of traditional classifiers for identifying patients with Systemic Lupus Erythematosus ( SLE ) in comparison with a newer Bayesian word vector method . Methods We obtained clinical notes for patients with SLE diagnosis along with controls from the Rheumatology Clinic ( 662 total patients ) . Sparse bag-of-words ( BOWs ) and Unified Medical Language System ( UMLS ) Concept Unique Identifiers ( CUIs ) matrices were produced using NLP pipelines . These matrices were subjected to several different NLP classifiers : neural networks , r and om forests , naïve Bayes , support vector machines , and Word2Vec inversion , a Bayesian inversion method . Performance was measured by calculating accuracy and area under the Receiver Operating Characteristic ( ROC ) curve ( AUC ) of a cross-vali date d ( CV ) set and a separate testing set . Results We calculated the accuracy of the ICD-9 billing codes as a baseline to be 90.00 % with an AUC of 0.900 , the shallow neural network with CUIs to be 92.10 % with an AUC of 0.970 , the r and om forest with BOWs to be 95.25 % with an AUC of 0.994 , the r and om forest with CUIs to be 95.00 % with an AUC of 0.979 , and the Word2Vec inversion to be 90.03 % with an AUC of 0.905 . Conclusions Our results suggest that a shallow neural network with CUIs and r and om forests with both CUIs and BOWs are the best classifiers for this lupus phenotyping task . The Word2Vec inversion method failed to significantly beat the ICD-9 code classification , but yielded promising results . This method does not require explicit features and is more adaptable to non-binary classification tasks . The Word2Vec inversion is hypothesized to become more powerful with access to more data . Therefore , currently , the shallow neural networks and r and om forests are the desirable class Output:	Many models achieved good predictive results in simple scenarios ( e.g. classification of cases and controls ) .
MS22522	*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 compare the outcomes of the current practice of liberally or routinely employing episiotomy to prevent perineal tears and pelvic floor relaxation ( control group ) to a policy of restricting episiotomy use to specific fetal and maternal indications ( experimental group ) . DESIGN : A r and omized controlled trial ( RCT ) . SETTING : Three university hospitals in Montreal . SUBJECTS : Seven hundred three low-risk women enrolled at 30 to 34 weeks of gestation were r and omized late in labor to the design ated trial arm , by parity , and followed up to 3 months postpartum . MAIN OUTCOME MEASURES : Antepartum and postpartum information on perineal trauma and pain , pelvic floor symptoms ( urinary incontinence ) , and sexual activity was collected through the use of st and ard question naires ; pelvic floor function was measured by electromyographic ( EMG ) perineometry . RESULTS : Restricting episiotomy use in primiparous women was associated with similar sutured perineal trauma to the liberal or routine approach . Multiparous women in the restricted episiotomy group more often gave birth with an intact perineum ( 31 % compared with 19 % , odds ratio ( OR ) = 1.85 , 95 % confidence interval ( CI ) = 1.09 to 3.16 ) . All but one 3rd/4th-degree perineal tear was associated with median episiotomy ( 46 of 47 in primiparous women and 6 of 6 among multiparous women ) . No difference between trial groups was found in postpartum perineal pain , antepartum and 3-month postpartum EMG perineometry , and urinary and pelvic floor symptoms . CONCLUSIONS : We found no evidence that liberal or routine use of episiotomy prevents perineal trauma or pelvic floor relaxation . Virtually all severe perineal trauma was associated with median episiotomy . Restriction of episiotomy use among multiparous women result ed in significantly more intact perineums and less perineal suturing Episiotomy is a widely-done intervention in childbirth , regardless of poor scientific evidence of its benefits . This r and omised controlled trial compares selective with routine use of a mediolateral episiotomy for women having first and second deliveries in 8 public maternity units in Argentina . 2606 women participated ; 1555 were nulliparous ( 778 in the selective group and 777 in the routine group ) and 1051 primiparous ( 520 in the selective group and 531 in the routine group ) . The two interventions compared were selective ( limited to specified maternal or fetal indications ) , and routine episiotomy ( following the hospital 's previous policy ) . Episiotomy was done in 30.1 % of deliveries in the selective , and 82.6 % in the routine group . The main outcome measure was severe perineal trauma . Severe perineal trauma was uncommon in both groups but was slightly less frequent in the selective group ( 1.2 % vs 1.5 % ) . Anterior perineal trauma was more common in the selective group but posterior perineal surgical repair , perineal pain , healing complications , and dehiscence were all less frequent in the selective group . Routine episiotomy should be ab and oned and episiotomy rates above 30 % can not be justified Women who had participated in a r and omised controlled trial of policies of restricted ( 10 % ) versus liberal ( 51 % ) episiotomy during spontaneous vaginal delivery were recontacted by postal question naire three years after delivery . Altogether 674 out of 1000 responded , and there was no evidence of a differential response rate between the two trial groups . Similar numbers of women in the two groups reported further deliveries , almost all of which had been vaginal and spontaneous . Fewer women allocated to restrictive use of episiotomy required perineal suturing after subsequent delivery , but this difference was not significant . Pain during sexual intercourse and incontinence of urine were equally reported in the two groups . The similarity in incontinence rates persisted when severity , type of incontinence , and subsequent deliveries were taken into account . Liberal use of episiotomy does not seem to prevent urinary incontinence or increase long term dyspareunia 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 OBJECTIVE : To evaluate the effect of mediolateral episiotomy on puerperal pelvic floor strength and dysfunction ( urinary and anal incontinence , genital prolapse ) . METHODS : Five hundred nineteen primiparous women were enrolled 3 months after vaginal delivery . Puerperae were divided in 2 groups : group A ( 254 women ) comprised the women who received mediolateral episiotomy and group B ( 265 women ) the women with intact perineum and first- and second-degree spontaneous perineal lacerations . Each woman was question ed about urogynecological symptoms and examined by digital test , vaginal perineometry , and uroflowmetric stop test score . Data were subjected to Student t test and Fisher exact test to assess , respectively , the difference between the mean values and the proportions within the sub population s. Using a simple logistic regression model to test an estimate of relative risk , we expressed the odds ratios of the variables considered with respect to the control population ( group B ) . RESULTS : No significant difference was found with regard to the incidence of urinary and anal incontinence and genital prolapse , whereas dyspareunia and perineal pain were significantly higher in the episiotomy group ( 7.9 % versus 3.4 % , P = .026 ; 6.7 % versus 2.3 % , P = .014 , respectively ) . Episiotomy was associated with significantly lower values , both in digital test ( 2.2 versus 2.6 ; P < .001 ) and in vaginal manometry ( 12.2 versus 13.8 cm water ; P < .001 ) , but not in uroflowmetric stop test . CONCLUSION : Mediolateral episiotomy does not protect against urinary and anal incontinence and genital prolapse and is associated with a lower pelvic floor muscle strength compared with spontaneous perineal lacerations and with more dyspareunia and perineal pain . LEVEL OF EVIDENCE : OBJECTIVE In 1999 , three r and omized controlled trials concluded that high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation ( HDC/HCT ) is no better than conventional chemotherapy for women with breast cancer . This study documents the impact of the trials on use of HDC/HCT and describes how hospitals reacted to the trials . DATA SOURCE We used patient-level data on 15,847 HDC/HCTs reported to the Center for International Blood and Marrow Transplant Research between 1994 and 2005 . STUDY DESIGN We report trends in total HDC/HCT procedure volume , compare the time to hospitals ' exit from the HDC/HCT market between research and non research hospitals , and document trends in hospital-specific volumes in the 2 years before exit . PRINCIPAL FINDINGS HDC/HCT volume declined from 3,108 in 1998 to 1,363 the year after trial results were released . In 2002 , only 76 procedures were performed . Teaching hospitals and the hospitals that participated in the trials were no slower to discontinue the procedure compared with nonteaching , nonparticipating hospitals . At the hospital level , volume declined steadily in the months before ab and onment . CONCLUSION The results suggest that comparative effectiveness research studies that report negative results can reduce spending , but specialists may be reluctant to relinquish cutting-edge technologies Output:	Mixed effects models estimated negative correlation between cross-time and cross-hospital variations in episiotomy rates , indicating reduced cross-hospital variation over time . Conclusions Our results suggested that there has been a gradual decline in episiotomy rates over the period 2003–2008 , and that synthesis of evidence showing harms from routine episiotomy had limited impact on practice patterns in the case of episiotomy .
MS22523	*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 study attempted to determine the best method of treatment for patients with recurrent preterm labor : administration of terbutaline via an automated , programmable , subcutaneous infusion pump or oral terbutaline . In this retrospective , controlled study , 32 patients diagnosed with recurrent preterm labor , as determined by persistent uterine contractions with cervical change , were treated with a programmable infusion pump adjusted to control uterine contraction frequency to < or = 4 contractions per hour . Patients in this group were matched for age , race , parity , gestational age and cervical dilation at diagnosis of recurrent preterm labor in subjects taking oral terbutaline . The patients receiving oral terbutaline were given an average of 6.5 mg every four to six hours to maintain uterine quiescence , while those in the pump group were given basal rates of terbutaline and in addition received four to six boluses per day ( < 3 mg/d total dose ) to achieve this outcome . Patients using the pump were more likely to reach term and less likely to fail tocolytic therapy than were those taking oral terbutaline . The terbutaline pump appeared to be more successful in prolonging pregnancies to term after the diagnosis of recurrent preterm labor than did oral terbutaline PURPOSE To compare the clinical benefit and cost-effectiveness of utilizing continuous subcutaneous terbutaline versus oral tocolytics following recurrent preterm labor . DESIGN Retrospective , 1:1 matched cohort . METHODOLOGY From prospect ively collected data in a nationwide , perinatal data base of women receiving outpatient services , we identified singleton gestations having recurrent preterm labor , stabilized during hospitalization , and subsequently treated with oral tocolytics ( PO group ) or continuous subcutaneous terbutaline infusion ( SQ group ) . Those without medically indicated delivery were eligible for inclusion . Each woman in the PO group was matched 1:1 by gestational age at recurrent preterm labor to a woman in the SQ group . A st and ardized cost model was applied to compare total antepartum hospital , nursery , and outpatient charges . Wilcoxon Signed Rank , paired t , and McNemar 's C2 test statistics were used for comparisons . PRINCIPAL FINDINGS 558 women were studied ( 279 per group ) . The PO group had less gestational gain following recurrent preterm labor than the SQ group ( 28.4 + /- 19.8 days vs. 33.9 + /- 19.0 days , respectively , P < .001 ) . The SQ group had less per patient charges ( $ ) for antepartum hospitalization ( 3,986 + /- 6,895 vs. 5,495 + /- 7,131 , P = .009 ) , and nursery ( 7,143 + /- 20,048 vs. 15,050 + /- 32,648 , P < .001 ) . Outpatient charges were less for the PO group ( 1,390 + /- 1,152 vs. 5,520 + /- 3,292 , P < .001 ) . Overall costs for those in the SQ group were $ 5,286 less per pregnancy compared to the PO group . CONCLUSION In this population , continuous subcutaneous terbutaline infusion was both a clinical ly beneficial and cost-effective treatment following recurrent preterm labor OBJECTIVE Our hypothesis was that use of the subcutaneous terbutaline pump does not affect maternal glucose tolerance . STUDY DESIGN With the 1-hour glucose tolerance test , we examined the incidence of glucose intolerance in 37 patients using the pump compared with that of 54 patients receiving oral terbutaline and 634 control subjects without risk factors for gestational diabetes . The frequency of gestational diabetes and the need for insulin to maintain glycemic control were subjected to chi 2 analysis . RESULTS The incidence of gestational diabetes was 6 % in the control subjects , 5 % in patients using the pump ( p = 0.8 ) , and 11 % in those on the oral therapy regimen ( p = 0.4 ) . A total of 8 % of controls who had gestational diabetes required both insulin and diet , compared with 100 % using the pump ( p less than 0.01 ) and 50 % on the oral terbutaline regimen ( p = 0.03 ) . CONCLUSION The incidence of gestational diabetes is not increased in patients receiving terbutaline via the subcutaneous pump . The use of terbutaline by any route significantly increases the need for insulin to achieve glycemic control To determine the efficacy of the terbutaline pump for the prevention of preterm delivery , patients in preterm labor defined by progressive cervical change underwent intravenous magnesium sulfate tocolysis ( with or without oral indomethacin , as necessary ) , and once labor was arrested , were r and omized to one of three treatment arms : terbutaline by pump , saline by pump ( blinded ) , or oral terbutaline . If recurrent preterm labor occurred despite maximization of therapy , the treatment arm was determined and therapy was changed ; saline pump and oral terbutaline were switched to terbutaline pump , terbutaline pump was switched to oral terbutaline . Patients who continued to labor were readmitted for aggressive intravenous therapy . Women r and omized to the terbutaline pump ( n = 15 ) , saline pump ( n = 12 ) , and oral terbutaline ( n = 15 ) groups were similar in terms of gravidity , parity , days of tocolysis before study entry , gestational age at entry , and cervical dilatation at entry . The mean gestational age at delivery was the same in all three groups ( 35 weeks ) , as were neonatal outcomes . Terbutaline by pump , saline by pump , and oral terbutaline appear equivalent for the prevention of preterm delivery . The terbutaline pump should remain experimental We examined pregnancy outcomes in women receiving nifedipine tocolysis having recurrent preterm labor ( RPTL ) . Singleton gestations enrolled for outpatient nursing surveillance and prescribed nifedipine tocolysis were identified ( N = 4748 ) . Women hospitalized for RPTL at < 35 weeks then resuming outpatient surveillance were included ( N = 1366 ) . Pregnancy outcomes of women resuming nifedipine ( N = 830 ) were compared with those having an alteration in treatment to continuous subcutaneous terbutaline ( N = 536 ) . Overall , 56.7 % ( 2692/4748 ) experienced RPTL . Half ( 50.7 % ) were stabilized and resumed outpatient surveillance with nifedipine or continuous subcutaneous terbutaline . Infants from women resuming nifedipine versus those with alteration of treatment to terbutaline were more likely to deliver at < 35 weeks ( 28.0 % versus 13.8 % ) , weigh < 2500 g ( 32.9 % versus 20.3 % ) , and require a stay in the neonatal intensive care unit ( 34.0 % versus 23.1 % ) , all P < 0.001 . Alteration of tocolytic treatment following RPTL result ed in a decreased incidence of preterm birth and low birth weight , result ing in less admission to the neonatal intensive care unit and fewer nursery days Output:	The authors conclude that subcutaneous terbutaline pump is beneficial and safe for maintenance of tocolysis based on all the available evidence . Although we found that the pump was beneficial for some outcomes ( i.e. , neonatal death , incidence of delivery < 32 weeks and < 37 weeks , and prolonging pregnancy ) , importantly , these benefits were rated as having low strength of evidence , which means that we have low confidence that the evidence reflects the true effect [ 22 ] .
MS22524	*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 Stepping impairments are associated with physical and cognitive decline in older adults and increased fall risk . Exercise interventions can reduce fall risk , but adherence is often low . A new exergame involving step training may provide an enjoyable exercise alternative for preventing falls in older people . Purpose To assess the feasibility and safety of unsupervised , home-based step pad training and determine the effectiveness of this intervention on stepping performance and associated fall risk in older people . Design Single-blinded two-arm r and omized controlled trial comparing step pad training with control ( no-intervention ) . Setting / Participants Thirty-seven older adults residing in independent-living units of a retirement village in Sydney , Australia . Intervention Intervention group ( IG ) participants were provided with a computerized step pad system connected to their TVs and played a step game as often as they liked ( with a recommended dose of 2–3 sessions per week for 15–20 minutes each ) for eight weeks . In addition , IG participants were asked to complete a choice stepping reaction time ( CSRT ) task once each week . Main Outcome Measures CSRT , the Physiological Profile Assessment ( PPA ) , neuropsychological and functional mobility measures were assessed at baseline and eight week follow-up . Results Thirty-two participants completed the study ( 86.5 % ) . IG participants played a median 2.75 sessions/week and no adverse events were reported . Compared to the control group , the IG significantly improved their CSRT ( F31,1 = 18.203 , p<.001 ) , PPA composite scores ( F31,1 = 12.706 , p = 0.001 ) , as well as the postural sway ( F31,1 = 4.226 , p = 0.049 ) and contrast sensitivity ( F31,1 = 4.415 , p = 0.044 ) PPA sub-component scores . In addition , the IG improved significantly in their dual-task ability as assessed by a timed up and go test/verbal fluency task ( F31,1 = 4.226 , p = 0.049 ) . Conclusions Step pad training can be safely undertaken at home to improve physical and cognitive parameters of fall risk in older people without major cognitive and physical impairments . Trial Registration Australian New Zeal and Clinical Trials Registry ACTRN12611001081909 Loss to follow-up is often hard to avoid in r and omised trials . This article suggests a framework for intention to treat analysis that depends on making plausible assumptions about the missing data and including all participants in sensitivity Background Computer-based interventions have demonstrated consistent positive effects on various physical abilities in older adults . This study aims to compare two training groups that achieve similar amounts of strength and balance exercise where one group receives an intervention that includes additional dance video gaming . The aim is to investigate the different effects of the training programs on physical and psychological parameters in older adults . Methods Thirty-one participants ( mean age ± SD : 86.2 ± 4.6 years ) , residents of two Swiss hostels for the aged , were r and omly assigned to either the dance group ( n = 15 ) or the control group ( n = 16 ) . The dance group absolved a twelve-week cognitive-motor exercise program twice weekly that comprised progressive strength and balance training supplemented with additional dance video gaming . The control group performed only the strength and balance exercises during this period . Outcome measures were foot placement accuracy , gait performance under single and dual task conditions , and falls efficacy . Results After the intervention between-group comparison revealed significant differences for gait velocity ( U = 26 , P = .041 , r = .45 ) and for single support time ( U = 24 , P = .029 , r = .48 ) during the fast walking dual task condition in favor of the dance group . No significant between-group differences were observed either in the foot placement accuracy test or in falls efficacy . Conclusions There was a significant interaction in favor of the dance video game group for improvements in step time . Significant improved fast walking performance under dual task conditions ( velocity , double support time , step length ) was observed for the dance video game group only . These findings suggest that in older adults a cognitive-motor intervention may result in more improved gait under dual task conditions in comparison to a traditional strength and balance exercise program . Trial registration This trial has been registered under IS RCT N05350123 ( http://www.controlled-trials.com BACKGROUND Older adults show increased risk of falling and major risk factors include impaired lower extremity muscle strength and postural balance . However , the potential positive effect of biofeedback-based Nintendo Wii training on muscle strength and postural balance in older adults is unknown . METHODS This r and omized controlled trial examined postural balance and muscle strength in community-dwelling older adults ( 75±6 years ) pre- and post-10 weeks of biofeedback-based Nintendo Wii training ( WII , n = 28 ) or daily use of ethylene vinyl acetate copolymer insoles ( controls [ CON ] , n = 30 ) . Primary end points were maximal muscle strength ( maximal voluntary contraction ) and center of pressure velocity moment during bilateral static stance . RESULTS Intention-to-treat analysis with adjustment for age , sex , and baseline level showed that the WII group had higher maximal voluntary contraction strength ( 18 % ) than the control group at follow up ( between-group difference = 269 N , 95 % CI = 122 ; 416 , and p = .001 ) . In contrast , the center of pressure velocity moment did not differ ( 1 % ) between WII and CON at follow-up ( between-group difference = 0.23 mm(2)/s , 95 % CI = -4.1 ; 4.6 , and p = .92 ) . For secondary end points , pre-to-post changes favoring the WII group were evident in the rate of force development ( p = .03 ) , Timed Up and Go test ( p = .01 ) , short Falls Efficacy Scale-International ( p = .03 ) , and 30-second repeated Chair St and Test ( p = .01 ) . Finally , participants rated the Wii training highly motivating at 5 and 10 weeks into the intervention . CONCLUSIONS Biofeedback-based Wii training led to marked improvements in maximal leg muscle strength ( maximal voluntary contraction ; rate of force development ) and overall functional performance in community-dwelling older adults . Unexpectedly , static bilateral postural balance remained unaltered with Wii training . The high level of participant motivation suggests that biofeedback-based Wii exercise may ensure a high degree of compliance to home- and /or community-based training in community-dwelling older adults Poor balance is considered a challenging risk factor for falls in older adults . Therefore , innovative interventions for balance improvement in this population are greatly needed . The aim of this study was to evaluate the effect of a new virtual-reality system ( the Balance Rehabilitation Unit [ BRU ] ) on balance , falls , and fear of falling in a population of community-dwelling older subjects with a known history of falls . In this study , 60 community-dwelling older subjects were recruited after being diagnosed with poor balance at the Falls and Fractures Clinic , Nepean Hospital ( Penrith , NSW , Australia ) . Subjects were r and omly assigned to either the BRU-training or control groups . Both groups received the usual falls prevention care . The BRU-training group attended balance training ( two sessions/week for 6 weeks ) using an established protocol . Change in balance parameters was assessed in the BRU-training group at the end of their 6-week training program . Both groups were assessed 9 months after their initial assessment ( month 0 ) . Adherence to the BRU-training program was 97 % . Balance parameters were significantly improved in the BRU-training group ( P < 0.01 ) . This effect was also associated with a significant reduction in falls and lower levels of fear of falling ( P < 0.01 ) . Some components of balance that were improved by BRU training showed a decline after 9 months post-training . In conclusion , BRU training is an effective and well-accepted intervention to improve balance , increase confidence , and prevent falls in the elderly Background and purpose Numerous interventions have been proposed to improve balance in older adults with varying degrees of success . A novel approach may be to use an off-the-shelf video game system utilizing real-time force feedback to train older adults . The purpose of this study is to investigate the feasibility of using Nintendo ’s Wii Fit for training to improve clinical measures of balance in older adults and to retain the improvements after a period of time . Methods Twelve healthy older adults ( aged > 70 years ) were r and omly divided into two groups . The experimental group completed training using Nintendo ’s Wii Fit game three times a week for 3 weeks while the control group continued with normal activities . Four clinical measures of balance were assessed before training , 1 week after training , and 1 month after training : Berg Balance Scale ( BBS ) , Fullerton Advanced Balance ( FAB ) scale , Functional Reach ( FR ) , and Timed Up and Go ( TUG ) . Friedman two-way analysis of variance by ranks was conducted on the control and experimental group to determine if training using the Wii Balance Board with Wii Fit had an influence on clinical measures of balance . Results Nine older adults completed the study ( experimental group n = 4 , control group n = 5 ) . The experimental group significantly increased their BBS after training while the control group did not . There was no significant change for either group with FAB , FR , and TUG . Conclusion Balance training with Nintendo ’s Wii Fit may be a novel way for older adults to improve balance as measured by the BBS OBJECTIVES To determine the long-term effects of three strength and balance exercise interventions on physical performance , fall-related psychological outcomes , and falls in older people . DESIGN A single-blinded , four-group , r and omized controlled trial . SETTING Community , Germany . PARTICIPANTS Community-dwelling adults aged 70 to 90 who had fallen in the past 6 months or reported fear of falling . INTERVENTION After baseline assessment , 280 participants were r and omly assigned to the control group ( CG ; no intervention ; n = 80 ) or one of three strength and balance exercise interventions ( the strength and balance group ( SBG ; strength and balance only ; n = 63 ) , the fitness group ( FG ; strength and balance plus endurance training ; n = 64 ) , or the multifaceted group ( MG ; strength and balance plus fall risk education ; n = 73 ) . The interventions consisted of 32 one-hour group sessions in 16 weeks . MEASUREMENTS Data on physical performance , fall-related psychological outcomes , and falls were collected for 24 months . RESULTS Mixed-effects regression analyses showed improved short- and long-term ( 12 and 24 months , respectively ) physical performance for the SBG and FG , particularly regarding mobility , balance , and walking speed ( P < .05 ) . The improvements in physical performance outcomes were most prominent in the FG . Fall-related psychological outcomes , number of falls , and injurious falls were not significantly different from in the control group . CONCLUSION Training focusing on strength , balance , and endurance can enhance physical performance for up to 24 months in community-dwelling older adults . These findings did not translate to improved fall-related psychological outcomes or reduced incidence of falls . This demonstrates the need for a different approach ( e.g. , regarding intervention dose and components ) to gain intervention benefits in the multiple domains that contribute to independence and well-being in older adults OBJECTIVE To compare the impacts of Tai Chi , a st and ard balance exercise program , and a video game balance board program on postural control and perceived falls risk . DESIGN R and omized controlled trial . SETTING Research laboratory . PARTICIPANTS Independent seniors ( N=40 ; 72.5±8.40 ) began the training , 27 completed . INTERVENTIONS Tai Chi , a st and ard balance exercise program , and a video game balance board program . MAIN OUTCOME MEASURES The following were used as measures : Timed Up & Go , One-Leg Stance , functional reach , Tinetti Performance Oriented Mobility Assessment , force plate center of pressure ( COP ) and time to boundary , dynamic posturography ( DP ) , Falls Risk for Older People-Community Setting , and Falls Efficacy Scale . RESULTS No significant differences were seen between groups for any outcome measures at baseline , nor were significant time or group × time differences for any field test or question naire . No group × time differences were seen for any COP measures ; however , significant time differences were seen for total COP , 3 of 4 anterior/posterior displacement and both velocity , and 1 displacement and 1 velocity medial/lateral measure across time for the entire sample . For DP , significant improvements in the overall score ( dynamic movement analysis score ) , and in 2 of the 3 linear and angular measures were seen for the sample . CONCLUSIONS The video game balance board program , which can be performed at home , was as effective as Tai Chi and the st and ard balance exercise program in improving postural control and balance dictated by the force plate postural sway and DP measures . This finding may have implication s for exercise adherence because the at-home nature of the intervention eliminates many obstacles to exercise training BACKGROUND physical therapy interventions that increase functional strength and balance have been shown to reduce falls in older adults . AIM this study compared a virtual reality group ( VRG ) and a control group ( CG ) . DESIGN r and omised controlled 6-week intervention with pre- and post-test evaluations . SETTING outpatient geriatric orthopaedic and balance physical therapy clinic . POPULATION forty participants were r and omised into two groups . METHOD the VRG received three different Nintendo ® Wii FIT balance interventions three times per week for 6 weeks and the CG received no intervention . RESULTS compared with the CG , post-intervention measurements showed significant improvements for the VRG in the 8-foot Up & Go test [ median decrease of 1.0 versus -0.2 s , ( P=0.038 ) and the Activities-specific Output:	However , a consensus between studies is the positive motivational aspect that the use of exergames provides .
MS22525	*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 provide evidence regarding the clinical efficacy of cognitive rehabilitation ( CR ) in early-stage Alzheimer disease ( AD ) . DESIGN Single-blind r and omized controlled trial comparing CR with relaxation therapy and no treatment . SETTING Outpatient , community-based setting . PARTICIPANTS Sixty-nine individuals ( 41 women , 28 men ; mean age 77.78 years , st and ard deviation 6.32 , range = 56 - 89 ) with a diagnosis of AD or mixed AD and vascular dementia and a Mini-Mental State Examination score of 18 or above , and receiving a stable dose of acetylcholinesterase-inhibiting medication . Forty-four family carers also contributed . INTERVENTION Eight weekly individual sessions of CR consisting of personalized interventions to address individually relevant goals supported by components addressing practical aids and strategies , techniques for learning new information , practice in maintaining attention and concentration , and techniques for stress management . MEASUREMENTS The primary outcomes were goal performance and satisfaction , assessed using the Canadian Occupational Performance Measure . Question naires assessing mood , quality of life and career strain , and a brief neuropsychological test battery were also administered . A subset of participants underwent functional magnetic resonance imaging ( fMRI ) . RESULTS CR produced significant improvement in ratings of goal performance and satisfaction , whereas scores in the other two groups did not change . Behavioral changes in the CR group were supported by fMRI data for a subset of participants . CONCLUSIONS The findings support the clinical efficacy of CR in early-stage AD . CR offers a means of assisting people with early-stage AD and their families in managing the effects of the condition The efficacy of a cognitive intervention consisting of training in face-name associations , spaced retrieval , and cognitive stimulation was tested in a sample of 37 patients ( 16 men , 21 women ) with probable Alzheimer disease ( AD ) . Patients with AD were r and omly assigned to receive either the cognitive intervention or a mock ( placebo ) intervention for 5 weeks . The placebo group then crossed over to receive the intervention . During the intervention , AD patients showed significant improvement in recall of personal information , face-name recall , and performance on the Verbal Series Attention Test . Improvement did not generalize to additional neuropsychologic measures of dementia severity , verbal memory , visual memory , word generation , or motor speed , or to caregiver-assessed patient quality of life . Results suggest that although face-name training , spaced retrieval , and cognitive stimulation may produce small gains in learning personal information and on a measure of attention , improvement does not generalize to overall neuropsychologic functioning or patient quality of life BACKGROUND Psychological therapy groups for people with dementia are widely used , but their cost-effectiveness has not been explored . AIMS To investigate the cost-effectiveness of an evidence -based cognitive stimulation therapy ( CST ) programme for people with dementia as part of a r and omised controlled trial . METHOD A total of 91 people with dementia , living in care homes or the community , received a CST group intervention twice weekly for 8 weeks ; 70 participants with dementia received treatment as usual . Service use was recorded 8 weeks before and during the 8-week intervention and costs were calculated . A cost-effectiveness analysis was conducted with cognition as the primary outcome , and quality of life as the secondary outcome . Cost-effectiveness acceptability curves were plotted . RESULTS Cognitive stimulation therapy has benefits for cognition and quality of life in dementia , and costs were not different between the groups . Under reasonable assumptions , there is a high probability that CST is more cost-effective than treatment as usual , with regard to both outcome measures . CONCLUSIONS Cognitive stimulation therapy for people with dementia has effectiveness advantages over , and may be more cost-effective than , treatment as usual OBJECTIVE The authors evaluated the efficacy of a new cognitive rehabilitation program on memory and functional performance of mildly impaired Alzheimer disease ( AD ) patients receiving a cholinesterase inhibitor . METHODS Twenty-five participants in the Cognitive Rehabilitation ( CR ) condition participated in two 45-minute sessions twice per week for 24 total sessions . CR training included face-name association tasks , object recall training , functional tasks ( e.g. , making change , paying bills ) , orientation to time and place , visuo-motor speed of processing , and the use of a memory notebook . Nineteen participants in the Mental Stimulation ( MS ) condition had equivalent therapist contact and number of sessions , which consisted of interactive computer games involving memory , concentration , and problem-solving skills . RESULTS Compared with the MS condition , participants in CR demonstrated improved performance on tasks that were similar to those used in training . Gains in recall of face-name associations , orientation , cognitive processing speed , and specific functional tasks were present post-intervention and at a 3-month follow-up . CONCLUSION A systematic program of cognitive rehabilitation can result in maintained improvement in performance on specific cognitive and functional tasks in mildly impaired AD patients The efficacy of a memory-training program to improve word-list recall and recognition was evaluated in 34 patients with probable Alzheimer 's disease ( AD ) . The patients , who were all taking donepezil throughout the 6-week intervention , were r and omly assigned to a cognitive intervention group or a control group . The Control group received didactic presentations but no formal memory training . Patients were assessed on neuropsychological tests before the 6-week training program , immediately after the training , and 8 weeks after completion of the training . Caregivers , who were blind to group assignment , completed activities of daily living ( ADLs ) and everyday memory question naires at all three timepoints . No significant main effects of group ( training vs. control ) or time were observed on any outcome measures , nor were any significant interactions found . In terms of " process " measures during the 6-week training program , the patients demonstrated modest improvement on recall and recognition of test material presented during the training sessions . These results suggest that although modest gains in learning and memory may be evident in AD patients who are taught specific strategies , the benefits do not generalize to other measures of neuropsychological functioning after a brief intervention 70 patients with probable Alzheimer 's disease were r and omly allocated to four groups : 17 patients received only social support , 18 cognitive training twice a week , in 17 cognitive training was combined with pyritinol 2 x 600 mg/day and in 18 cognitive training was combined with phosphatidylserine 2 x 200 mg/day . Treatment duration was 6 months . Before and after treatment , the patients underwent neuropsychological testing as well as measurement of the regional cerebral metabolic rate for glucose using positron emission tomography and 18F-2-fluoro-2-deoxy-D-glucose . Before treatment the groups were comparable in respect to resting and activated glucose pattern achieved by a visual recognition task . Electrophysiological changes were assessed as EEG power , globally and in 4 frequency b and s. This 6-month study in four groups of patients with Alzheimer 's disease indicated that phosphatidylserine treatment has an effect on different measures of brain function . Since neuropsychological improvements were best documented after 8 and 16 weeks and faded towards the end of the treatment period , it must be concluded that this symptomatic therapy is mainly of short-term benefit and was overcome by the progressive pathological changes at the end of the treatment period BACKGROUND Cholinesterase inhibitors produce small improvements in cognitive and global assessment s in Alzheimer 's disease . We aim ed to determine whether donepezil produces worthwhile improvements in disability , dependency , behavioural and psychological symptoms , carers ' psychological wellbeing , or delay in institutionalisation . If so , which patients benefit , from what dose , and for how long ? METHODS 565 community-resident patients with mild to moderate Alzheimer 's disease entered a 12-week run-in period in which they were r and omly allocated donepezil ( 5 mg/day ) or placebo . 486 who completed this period were rer and omised to either donepezil ( 5 or 10 mg/day ) or placebo , with double-blind treatment continuing as long as judged appropriate . Primary endpoints were entry to institutional care and progression of disability , defined by loss of either two of four basic , or six of 11 instrumental , activities on the Bristol activities of daily living scale ( BADLS ) . Outcome assessment s were sought for all patients and analysed by logrank and multilevel models . FINDINGS Cognition averaged 0.8 MMSE ( mini-mental state examination ) points better ( 95 % CI 0.5 - 1.2 ; p<0.0001 ) and functionality 1.0 BADLS points better ( 0.5 - 1.6 ; p<0.0001 ) with donepezil over the first 2 years . No significant benefits were seen with donepezil compared with placebo in institutionalisation ( 42 % vs 44 % at 3 years ; p=0.4 ) or progression of disability ( 58 % vs 59 % at 3 years ; p=0.4 ) . The relative risk of entering institutional care in the donepezil group compared with placebo was 0.97 ( 95 % CI 0.72 - 1.30 ; p=0.8 ) ; the relative risk of progression of disability or entering institutional care was 0.96 ( 95 % CI 0.74 - 1.24 ; p=0.7 ) . Similarly , no significant differences were seen between donepezil and placebo in behavioural and psychological symptoms , carer psychopathology , formal care costs , unpaid caregiver time , adverse events or deaths , or between 5 mg and 10 mg donepezil . INTERPRETATION Donepezil is not cost effective , with benefits below minimally relevant thresholds . More effective treatments than cholinesterase inhibitors are needed for Alzheimer 's disease Objective : To determine the efficacy of cognitive stimulation therapy ( CST ) in the treatment of neuropsychiatric symptoms in patients with Alzheimer ’s disease . Design : A r and omized , controlled , rater-blind clinical trial . Setting : The military sanatorium . Subjects : Thirty-two patients with mild to moderate Alzheimer ’s disease exhibiting marked neuropsychiatric symptoms were included in the study . Intervention : All 32 patients were r and omly assigned to a cognitive stimulation therapy group ( n = 16 ) or a control group ( n = 16 ) for 10 weeks . Main measure : The efficacy measures included the Mini Mental State Examination and the Neuropsychiatric Inventory . Results : Patients receiving cognitive stimulation therapy showed a greater improvement in the Neuropsychiatric Inventory total score ( mean change — 2.06 points versus 0.00 points , t = -4.766 , P<0.001 ) and in the Mini Mental State Examination total score ( mean change 0.81 points versus —0.19 points , t = 3.106 , P = 0.004 ) compared to control at week 10 . Analysis of the individual Neuropsychiatric Inventory domains revealed a statistically significant benefit for cognitive stimulation therapy-treated patients in the areas of apathy ( mean change —1.06 points versus —0.31 points , P = 0.017 ) and depression/dysphoria ( mean change —0.50 points versus 0.06 points , P = 0.047 ) . There were no statistically significant benefits for cognitive stimulation therapy-treated patients in the other individual Neuropsychiatric Inventory domains or in the caregiver distress score . Conclusions : Cognitive stimulation therapy has significant efficacy in lowering apathy and depression symptomatology and in the Mini Mental State Examination in patients with mild to moderate Alzheimer ’s disease R and omised controlled trials are widely accepted as the most reliable method of determining effectiveness , but most trials have evaluated the effects of a single intervention such as a drug . Recognition is increasing that other , non-pharmacological interventions should also be rigorously evaluated.1 - 3 This paper examines the design and execution of research required to address the additional problems result ing from evaluation of complex interventions —that is , those “ made up of various interconnecting parts.”4 The issues dealt with are discussed in a longer Medical Research Council paper ( www.mrc.ac.uk/complex_packages.html ) . We focus on r and omised trials but believe that this approach could be adapted to other design s when they are more appropriate . # # # # Summary points Complex interventions are those that include several components The evaluation of complex interventions is difficult because of problems of developing , identifying , documenting , and reproducing the intervention A phased approach to the development and evaluation of complex interventions is proposed to help research ers define clearly where they are in the research process Evaluation of complex interventions requires use of qualitative and quantitative evidence There are specific difficulties in defining , developing , documenting , and reproducing complex interventions that are subject to more variation than a drug . A typical example would be the design of a trial to evaluate the benefits of specialist stroke units . Such a trial would have to consider the expertise of various health professionals as well as investigations , drugs , treatment guidelines , and arrangements for discharge and follow up . Stroke units may also vary in terms of organisation , management , and skill mix . The active components of the stroke unit may be difficult to specify , making it difficult to replicate the intervention . The box gives other examples of complex interventions . # # # # Examples of complex interventions Service delivery and organisation : Stroke units Hospital at home Interventions directed at health professionals ' behaviour : Strategies for implementing guidelines Computerised decision support Community interventions : Community Output:	Only the domain of global cognitive functioning , as measured by Mini-Mental State Examination , showed significant intervention effects . No effects were observed in the remaining domains .
MS22526	*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 cross-over trial of herpes simplex virus type 2 (HSV-2)-suppressive therapy ( valacyclovir , 500 mg twice daily , or placebo for 8 weeks , a 2-week washout period , then the alternative therapy for 8 weeks ) was conducted among 20 Peruvian women coinfected with HSV-2 and human immunodeficiency virus type 1 ( HIV-1 ) who were not on antiretroviral therapy . Plasma sample s ( obtained weekly ) and endocervical swab specimens ( obtained thrice weekly ) were collected for HIV-1 RNA polymerase chain reaction . Plasma HIV-1 level was significantly lower during the valacyclovir arm , compared with the placebo arm ( -0.26 log10 copies/mL , a 45 % decrease [ P < .001 ] ) , as was cervical HIV-1 level ( -0.35 log10 copies/swab , a 55 % decrease [ P < .001 ] ) . Suppressive HSV-2 therapy has the potential to reduce HIV-1 infectiousness and slow HIV-1 disease progression BACKGROUND Epidemiologic data suggest that infection with herpes simplex virus type 2 ( HSV-2 ) is associated with increased genital shedding of human immunodeficiency virus type 1 ( HIV-1 ) RNA and HIV-1 transmissibility . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of HSV suppressive therapy with valacyclovir ( at a dose of 500 mg twice daily ) in Burkina Faso among women who were seropositive for HIV-1 and HSV-2 ; all were ineligible for highly active antiretroviral therapy . The patients were followed for 24 weeks ( 12 weeks before and 12 weeks after r and omization ) . Regression models were used to assess the effect of valacyclovir on the presence and quantity of genital and plasma HIV-1 RNA and genital HSV-2 DNA during treatment , adjusting for baseline values , and to evaluate the effect over time . RESULTS A total of 140 women were r and omly assigned to treatment groups ; 136 were included in the analyses . At enrollment , the median CD4 cell count was 446 cells per cubic millimeter , and the mean plasma viral load was 4.44 log10 copies per milliliter . With the use of summary - measures analysis , valacyclovir therapy was found to be associated with a significant decrease in the frequency of genital HIV-1 RNA ( odds ratio , 0.41 ; 95 % confidence interval [ CI ] , 0.21 to 0.80 ) and in the mean quantity of the virus ( log(10 ) copies per milliliter , -0.29 ; 95 % CI , -0.44 to -0.15 ) . However , there was no significant decrease in detection of HIV ( risk ratio , 0.93 ; 95 % CI , 0.81 to 1.07 ) . HSV suppressive therapy also reduced the mean plasma HIV-1 RNA level by 0.53 log(10 ) copy per milliliter ( 95 % CI , -0.72 to -0.35 ) . Repeated- measures analysis showed that these effects became significantly stronger during the 3 months of follow-up . CONCLUSIONS HSV suppressive therapy significantly reduces genital and plasma HIV-1 RNA levels in dually infected women . This finding may have important implication s for HIV control . ( Clinical Trials.gov number , NCT00158509 [ Clinical Trials.gov ] . ) BACKGROUND Herpes simplex virus ( HSV ) suppressive therapy reduces genital and plasma human immunodeficiency virus type 1 ( HIV-1 ) RNA over periods up to 3 months , but the long-term effect is unknown . METHODS A total of 484 HIV-1 and HSV type 2 seropositive Tanzanian women aged 16 - 35 years were enrolled in a r and omized placebo-controlled trial of acyclovir administered at a dosage of 400 mg twice daily . Cervico-vaginal lavage and blood sample s were collected at 6 months , 12 months , and 24 months for quantification of genital and plasma HIV-1 RNA and genital HSV DNA . Primary outcomes were detection and quantity of cervico-vaginal HIV-1 RNA at 6 months . RESULTS At 6 months , there was little difference between the acyclovir and placebo arms for cervico-vaginal HIV-1 RNA detection ( 88 [ 41 .3 % ] of 213 vs 84 [ 44 .0 % ] of 191 ; odds ratio [ OR ] , 0.90 ; 95 % confidence interval [ CI ] , 0.60 - 1.33 ) , HSV DNA detection ( 20 [ 9 .4 % ] of 213 vs 22 [ 11 .5 % ] of 191 ; OR , 0.80 ; 95 % CI , 0.42 - 1.51 ) , genital HIV or HSV loads , or plasma HIV-1 RNA load . Estimated median adherence was 91 % . There was a suggestion of an impact on cervico-vaginal HIV-1 RNA detection among women with estimated adherence 90 % ( OR , 0.74 ; 95 % CI , 0.50 - 1.09 ) when data from all 3 visits were included . CONCLUSIONS Acyclovir administered at a dosage of 400 mg twice daily is unlikely to be a useful long-term intervention to reduce HIV transmission . The lack of effect on HIV may be attributable to suboptimal adherence or treatment regimen Genital HIV-1 RNA quantity predicts risk of heterosexual HIV-1 transmission independently of plasma HIV-1 concentration . Elucidating the Insidious Transmission of a Deadly Pathogen The deadly HIV-1 retrovirus that causes AIDS has been a scourge of humanity for nearly 30 years . Although combination therapy with antiretroviral drugs has proved successful , the complex drug regimen and great cost have prevented their widespread use in the developing world where they are most needed . The goal of developing a vaccine that would protect individuals from becoming infected with HIV-1 has remained elusive . Given that 90 % of all HIV infections worldwide are due to sexual transmission , there has been much interest in developing new strategies that could block HIV infection through the genital mucosa . However , the mechanisms underlying mucosal transmission of HIV are still poorly understood . Higher amounts of HIV-1 in genital secretions are thought to reflect a greater chance of sexual transmission , but testing this correlation is a difficult undertaking . Baeten and colleagues have taken on this challenge with their prospect i ve study in Africa of 2521 heterosexual serodiscordant couples ( one partner is HIV-infected and the other partner is not ) . These investigators evaluated the relationship between the quantity of HIV-1 RNA in the genital secretions of the infected partner and the risk of HIV-1 transmission to the uninfected partner in each couple . They tested the amount of HIV-1 RNA in endocervical swabs from 1805 HIV-1–infected women including 46 women known to have transmitted the virus to their male partners . They also tested the amount of HIV-1 RNA in semen from 716 men , including 32 who had transmitted HIV-1 to their female partners . The authors demonstrate that higher concentrations of HIV-1 RNA in genital secretions are associated with a greater risk of heterosexual transmission of HIV-1 , and that these concentrations provide a new biomarker for predicting the infectiousness of HIV-1–infected individuals . The authors propose that HIV-1 RNA concentrations in genital secretions could also be used as a biomarker to monitor the efficacy of new microbicides and other interventions design ed to block mucosal transmission of the virus . High plasma HIV-1 RNA concentrations are associated with an increased risk of HIV-1 transmission . Although plasma and genital HIV-1 RNA concentrations are correlated , no study has evaluated the relationship between genital HIV-1 RNA and the risk of heterosexual HIV-1 transmission . In a prospect i ve study of 2521 African HIV-1 serodiscordant couples , we assessed genital HIV-1 RNA quantity and HIV-1 transmission risk . HIV-1 transmission linkage was established within the partnership by viral sequence analysis . We tested endocervical sample s from 1805 women , including 46 who transmitted HIV-1 to their partner , and semen sample s from 716 men , including 32 who transmitted HIV-1 to their partner . There was a correlation between genital and plasma HIV-1 RNA concentrations : For endocervical swabs , Spearman ’s rank correlation coefficient ρ was 0.56 , and for semen , ρ was 0.55 . Each 1.0 log10 increase in genital HIV-1 RNA was associated with a 2.20-fold ( for endocervical swabs : 95 % confidence interval , 1.60 to 3.04 ) and a 1.79-fold ( for semen : 95 % confidence interval , 1.30 to 2.47 ) increased risk of HIV-1 transmission . Genital HIV-1 RNA independently predicted HIV-1 transmission risk after adjusting for plasma HIV-1 quantity ( hazard ratio , 1.67 for endocervical swabs and 1.68 for semen ) . Seven female-to-male and four male-to-female HIV-1 transmissions ( incidence < 1 % per year ) occurred from persons with undetectable genital HIV-1 RNA , but in all 11 cases , plasma HIV-1 RNA was detected . Thus , higher genital HIV-1 RNA concentrations are associated with greater risk of heterosexual HIV-1 transmission , and this effect was independent of plasma HIV-1 concentrations . These data suggest that HIV-1 RNA in genital secretions could be used as a marker of HIV-1 sexual transmission risk To explore the mechanism by which herpes simplex virus (HSV)-2 infection is related to HIV-1 acquisition , we conducted in situ analysis of the cellular infiltrate from sequential biopsies of HSV-2 lesions from patients on and off antiviral therapy . CD4 + and CD8 + T cells and a mixed population of plasmacytoid and myeloid dendritic cells ( DCs ) , including cells expressing the C-type lectin receptor DC-SIGN , persisted at sites of HSV-2 reactivation for months after healing , even with daily antiviral therapy . The CD4 + T cells that persisted reacted to HSV-2 antigen , were enriched for expression of the chemokine receptor CCR5 , and were contiguous to DCs expressing the interleukin-3 receptor CD123 or DC-SIGN . Ex vivo infection with a CCR5-tropic strain of HIV-1 revealed greater concentrations of integrated HIV-1 DNA in cells derived from healed genital lesion biopsies than in cells from control skin biopsies . The persistence and enrichment of HIV receptor – positive inflammatory cells in the genitalia help explain the inability of anti – HSV-2 therapy to reduce HIV acquisition Background Retrospective cohort studies of tuberculosis suggest that active tuberculosis accelerates the progression of HIV infection . The validity of these findings has been question ed because of their retrospective design , diverse study population s , variable compliance with anti-tuberculous therapy and use of anti-retroviral medication . To assess the impact of tuberculosis on survival in HIV infection we performed a prospect i ve study among HIV-infected Ug and an adults with and without tuberculosis . Methods In a prospect i ve cohort study , 230 patients with HIV-associated tuberculosis and 442 HIV-infected subjects without tuberculosis were followed for a mean duration of 19 months for survival . To assess changes in viral load over 1 year , 20 pairs of tuberculosis cases and controls were selected and matched according to baseline CD4 lymphocyte count , age , sex and tuberculin skin test status . Results During the follow-up period , 63 out of of 230 tuberculosis cases ( 28 % ) died compared with 85 out of 442 controls ( 19 % ) , with a crude risk ratio of 1.4 [ 95 % confidence interval ( CI ) , 1.07–1.87 ] . Most deaths occurred in patients with CD4 lymphocyte counts < 200 × 106 cells/l at baseline ( n = 99 ) and occurred with similar frequency in the tuberculosis cases ( 46 % ) and the controls ( 44 % ) . When the CD4 lymphocyte count was > 200 × 106 /l , however , the relative risk of death in HIV-associated tuberculosis was 2.1 ( 95 % CI , 1.27–3.62 ) compared with subjects without tuberculosis . For subjects with a CD4 lymphocyte count > 200 × 106/l , the 1-year survival proportion was slightly lower in the cases than in the controls ( 0.91 versus 0.96 ) , but by 2 years the survival proportion was significantly lower in the cases than in the controls ( 0.84 versus 0.91;P < 0.02 ; log-rank test ) . For subjects with a CD4 lymphocyte count of 200 × 106 cells/l or fewer , the survival proportion at 1 year for the controls was lower than cases ( 0.59 versus 0.64 Output:	Coinfections may increase HIV viral load in population s where they are prevalent , thereby facilitating HIV transmission . These effects may be reversed with treatment .
MS22527	*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 present study tested the extent to which age and obesity predicted impulsive choices for food and monetary outcomes and tested how a brief mindful-eating training would alter delay discounting for food and money choices compared with control groups . Method : First , 172 adolescents ( Mage = 13.13 years ) and 176 ( Mage = 23.33 years ) adults completed the Food Choice Question naire ( FCQ ) and Monetary Choice Question naire ( MCQ ) as measures of food and money delay discounting , respectively . Then , participants returned to the lab and were r and omly assigned to complete a brief mindful-eating training , watch a DVD on nutrition , or serve as a control . Participants completed the FCQ and MCQ again as a postmanipulation measure . Results : Participants with high percent body fat ( PBF ) were more impulsive for food than those with low PBF . Adults with high PBF were also more impulsive for money compared with adults with low PBF ; no PBF-related differences were found for adolescents . Participants in the mindful-eating group exhibited more self-controlled choices for food , but not for money . The control conditions did not exhibit changes . Conclusion : The study suggests that individuals with high PBF make more impulsive food choices relative to those with low PBF , which could increase the risk of obesity over time . It also is the first to demonstrate shifts in choice patterns for food and money using a brief mindful-eating training with adolescents . Mindful eating is a beneficial strategy to reduce impulsive food choice , at least temporarily , that may impede weight gain Obese individuals tend to behave more impulsively than healthy weight individuals across a variety of measures , but it is unclear whether this pattern can be altered . The present study examined the effects of a mindful eating behavioral strategy on impulsive and risky choice patterns for hypothetical food and money . In Experiment 1 , 304 participants completed computerized delay and probability discounting tasks for food-related and monetary outcomes . High percent body fat ( PBF ) predicted more impulsive choice for food , but not small-value money , replicating previous work . In Experiment 2 , 102 r and omly selected participants from Experiment 1 were assigned to participate in a 50-min workshop on mindful eating or to watch an educational video . They then completed the discounting tasks again . Participants who completed the mindful eating session showed more self-controlled and less risk-averse discounting patterns for food compared to baseline ; those in the control condition discounted similarly to baseline rates . There were no changes in discounting for money for either group , suggesting stimulus specificity for food for the mindful eating condition Obesity and cigarette smoking are often cited separately as the top two preventable causes of death in the United States ; however , little research has explored the factors associated with being both obese and a smoker . Delay discounting is a behavioral characteristic that may underlie both of these conditions/behaviors . Delay discounting describes the extent to which an individual discounts the value of an outcome because of a delay in its occurrence . Higher rates of discounting are often considered as an index of impulsivity and have been linked with obesity and cigarette smoking . No research to date has explored delay discounting in a sample of obese smokers . For this study , adolescent smokers classified as obese ( body mass index > 95th percentile ) and healthy weight ( body mass index between the 5th and 85th percentiles ) were compared on a laboratory assessment of delay discounting . Obese smokers discounted significantly more by delay than healthy weight smokers . This difference remained statistically significant even after controlling for demographic variables that differed across groups . These findings suggest that the relationships between delay discounting and obesity and cigarette smoking may be additive , such that extreme discounting might proportionally increase the risk of becoming an obese smoker . However , future prospect i ve study is needed to fully determine the veracity of this hypothesis Output:	Conclusions This review suggests that the mixed evidence to date is a result of method ological heterogeneity , and that future studies should utilise ‘ best practice ’ methods
MS22528	*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 Our purpose was to determine whether intracervical placement of laminaria stalks would improve the effectiveness of inducing termination of pregnancies in the second trimester by intra-amniotic injection of prostagl and in F(2)alpha . STUDY DESIGN This is a prospect i ve r and omized clinical trial conducted at Gynecology Department , Lis Maternity Hospital . Fifty women admitted for indicated second trimester pregnancy termination were r and omly assigned to receive either intracervical placement of laminaria ( n = 25 ) or not ( n = 25 ) , with concurrent use of intra-amniotic injection of prostagl and in F(2)alpha and concentrated oxytocin . The outcome measures were : time from induction to delivery and the side effects and complications of treatment . RESULTS There was no significant difference in the mean interval from induction to delivery in the laminaria and no laminaria groups , being 20 + /- 1.3 ( 8 - 30 ) h versus 19 + /- 1.0 ( 8 - 26 ) h , respectively . In addition , this interval was not different in subgroups of primiparas or multiparas . Other outcome measures such as retained placenta ( 4 % in both groups ) , post-partum hemorrhage ( 4 % in both groups ) gastro-intestinal side effects , fever , and use of analgesia were not significantly different between both groups . CONCLUSION We found no additional value in placing laminaria stalks when using intra-amniotic injection of prostagl and in F(2)alpha followed by concentrated oxytocin infusion for second trimester termination of pregnancy Objective The aim of this r and omized prospect i ve study was to compare efficacy and side effects of saline moistened misoprostol with dry misoprostol , administered 800 μg intravaginally every 6 h up to a maximum of 3 doses in 24 h for second trimester pregnancy termination . Material s and methods A total of 81 women seeking termination of second trimester pregnancy ( 55 fetal death , 17 fetal structural anomaly , 5 chromosomal abnormality , 4 other reasons ) were r and omly assigned to one of two treatment groups : ( 1 ) intravaginal non-moistened ( dry ) misoprostol in group A ( n = 40 ) or ( 2 ) misoprostol moistened with 3 ml of saline in group B ( n = 41 ) . Results All of the patients in either group aborted within 48 h ( 100 % success rate ) . Delivery was achieved in a median ( interquartile range ) of 13 ( 40 ) h with the group A protocol and 12 ( 36 ) h with the group B protocol ( P = 0.652 ) . Delivery with first dose , delivery within 12 h and delivery within 24 h were similar ( P > 0.05 ) in group B ( 34.1 , 87.5 and 60 % , respectively ) and group A ( 25 , 82.9 , 46.3 , respectively ) . Both treatment regimens were tolerable and with similar side effects . Conclusion Misoprostol moistened with saline was not more effective than dry misoprostol for second trimester pregnancy termination BACKGROUND When compared with the conventional surgical evacuation for the treatment of miscarriage , medical evacuation has been largely accepted as an effective and safe management . However , there is a lack of data on the long-term reproductive outcome of these two treatment modalities , which is crucial in patient counselling . The current study evaluates and compares the long-term fertility and pregnancy outcome following these two treatments . METHODS A cohort of 604 women enrolled in a previous r and omized controlled trial comparing medical and surgical evacuation for miscarriage were followed up prospect ively by telephone interview at a median of 6 ( range 4 - 9 ) years using a structured question naire . RESULTS A total of 423 women were contacted and four declined to participate ( response rate 69.4 % ) . Of these , 261 women ( 131 medical and 130 surgical evacuations ) had attempted to become pregnant since the miscarriage . There were no differences in their baseline characteristics including age , reproductive and contraceptive history . The natural conception rates were the same ( 97.7 % , P = 0.99 ) and the cumulative pregnancy rates were similar between groups , being 60 and 80 % at 12 and 24 months respectively . The median time-to-pregnancy was 8 months in both groups ( P = 0.97 ) and the subsequent live birth rates ( 85.2 versus 88.2 % , P = 0.72 ) result ing from the immediate pregnancy following previous treatment were similar . CONCLUSIONS The long-term conception rate and pregnancy outcome are not different following medical or surgical evacuation for miscarriage . Women should be reassured that their long-term fertility potential will not be compromised after medical treatment Two doses , 200 and 400 micrograms , of misoprostol , administered vaginally every 12 hours , up to four times , were tested in 101 and 133 healthy women , respectively , for interruption of pregnancies with 35 through 77 days of amenorrhea . The proportion of women who aborted increased with longer duration of treatment and was significantly higher with 400 than with 200 micrograms ( 66 versus 46 percent at 48 hours ) . Significance was maintained after controlling by age , body weight , parity , previous abortion and gestational age . Abortions were classified as incomplete or complete , according to the presence or not of embryonic tissue in the uterine cavity , diagnosed by vaginal sonography . Vacuum aspiration was carried out in all cases not classified as complete abortion 48 hours after the initiation of treatment , or earlier in case of persistent bleeding or woman 's request . The possibility of increasing effectiveness by using higher dose , shorter intervals or longer duration of treatment is discussed OBJECTIVE The purpose of this study was to estimate whether the efficacy of treatment with intravaginal misoprostol for first-trimester pregnancy failure is enhanced by the addition of saline solution . STUDY DESIGN Eighty women with embryonic/fetal death or anembryonic pregnancy were assigned r and omly to receive either 800 microg of misoprostol with saline solution ( group I , 41 women ) or without ( group II , 39 women ) . Treatment was repeated on day 3 if the gestational sac remained . Curettage was performed if the gestational sac remained on day 8 or as necessary during at least 30 days of follow-up . Data were analyzed with the Student t test and the chi(2 ) or Fisher exact test . RESULTS By the first follow-up visit , 73 % ( group I ) and 64 % ( group II ) of women passed the gestational sac ( P=.38 ) . By the second follow-up visit , expulsion rates were 83 % and 87 % , respectively ( P=.59 ) . Five subjects in each group underwent curettage . CONCLUSION Misoprostol is effective for the treatment of failed first-trimester pregnancy . The expulsion rate is not improved by adding saline solution BACKGROUND We aim ed to compare patients ' health-related quality of life after a misoprostol strategy to a curettage in women with early pregnancy failure after failed expectant management . METHODS A multicentre r and omized clinical trial was performed in The Netherl and s. In all , 154 women with early pregnancy failure confirmed at ultrasonography who had been managed expectantly unsuccessfully for > or = 1 week were r and omly assigned to undergo either treatment with misoprostol ( n=79 ) or curettage ( n=75 ) . The main outcome measures were health-related quality of life and satisfaction with treatment . RESULTS In the misoprostol strategy 47 % of the women needed additional curettage , as compared to 4 % after curettage . In both groups , health-related quality of life was impaired most severely 2 days after treatment . In the misoprostol group , health-related quality of life was more severely impaired ; after 2 days this was due to more pain and after 2 and 6 weeks this was due to a worse general health perception . Health-related quality of life was temporarily significantly more impaired in women in whom misoprostol failed as compared to women in whom misoprostol treatment was successful . In both treatment groups , an equal percentage of women ( 58 % ) would choose the same treatment in the future . In women treated with misoprostol , however , this choice depended on the initial success of misoprostol : in cases where misoprostol had caused complete evacuation , 76 % of the women would opt for the same treatment , whereas only 38 % of women who needed curettage after unsuccessful misoprostol would do so ( P<0.01 ) . CONCLUSION Our study shows that , although both the misoprostol strategy and the curettage strategy result ed in complete evacuation in the end , women are willing to accept some disadvantages of misoprostol to avoid curettage . A treatment inconvenience using misoprostol is accepted as long as initial evacuation rate is high . This finding should be an integral part of counselling women when deciding upon management of early pregnancy failure A total of 85 women with antepartum fetal death between 14 and 42 weeks gestation was r and omly assigned to one of two regimens of intravenous infusion of the prostagl and in analogue 16‐phenoxy‐17 , 18 , 19 , 20‐tetranor‐PGE2‐methylsulphonamide ( sulprostone ) for inducing labour . Women received either 1 μg/min until delivery or the commonly recommended treatment of 1500 μg in 8 h followed by another , identical course of treatment if delivery did not occur within 24 h. The 1 μg/min dose schedule used half the amount of prostagl and in and result ed in statistically significantly fewer gastrointestinal side‐effects compared with the conventional treatment . All women were delivered vaginally and there were no differences in induction‐to‐delivery intervals between the two treatments . Sulprostone infused at a rate of 1 μg/min result ed in a 50 % chance of being delivered within 12 h and a 90 % chance of being delivered within 24 h , with an overall frequency of side‐effects of 20 % OBJECTIVE To compare the efficacy of intramuscular methotrexate plus vaginal misoprostol to vaginal misoprostol alone in completing abortion in women with non-viable early first trimester pregnancy . METHOD Twenty-one women with non-viable pregnancy up to 49 days gestation were r and omized to receive intramuscular methotrexate , followed 2 days later by vaginal misoprostol or misoprostol alone . We also collected patient satisfaction information . RESULT Complete abortion occurred in all 12 ( 100 % ) women in the combined group and eight of nine ( 89 % , RR = 1.13 , CI 0.89 - 1.42 ) women in the misoprostol only group . Of the women , 75 % rated their experience as good and would choose medical management again . CONCLUSION Either methotrexate plus misoprostol or misoprostol alone effectively completed abortion in women with non-viable early pregnancy and represent acceptable medical alternatives to surgery or expectant management BACKGROUND Dilatation and curettage ( D&C ) has been the usual treatment for early pregnancy failure ( EPF ) . Medical management with misoprostol may be an effective alternative . Bleeding patterns during and after medical management of EPF are unknown . METHODS A prospect i ve cohort study was conducted at University-based clinics and physician offices . Eighty women < 11 weeks estimated gestational age with a diagnosis of missed abortion or fetal demise were enrolled . Treatment consisted of either 800 micro g of moistened ( 2 ml of saline ) or dry vaginal misoprostol . Self-reported bleeding and sanitary product usage were recorded in a daily 2 week diary . Haemoglobin was assessed at enrollment and 2 weeks later . RESULTS After misoprostol treatment , patients reported bleeding or spotting every day for the 14 days observed . Self-assessed heavy bleeding days were few ( median 3 ) and usually occurred immediately after treatment . Sanitary pad use was highly variable ( mean 30.5 , range 2 - 125 pads over the 2 week period ) and not related to changes in haemoglobin . The mean decrease in haemoglobin was 0.5 g/dl ( SD 1.2 ) . Complete expulsion without D&C occurred in 85 % of subjects . CONCLUSIONS Bleeding for at least 2 weeks after vaginal misoprostol for EPF is common . Heavy bleeding is usually limited to a few days after treatment . Clinical ly important changes in haemoglobin are rare 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 Output:	Available evidence from r and omised trials suggests that medical treatment with vaginal misoprostol may be an acceptable alternative to surgical evacuation or expectant management . In general , side effects of medical treatment were minor , consisting mainly of nausea and diarrhoea . There were no major differences in effectiveness between different routes of administration .
MS22529	*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 object of this study was to compare the biological outcome ( oocyte maturity , fertilization , cleavage ) and the clinical outcome after a ' long ' ( 15 - 24 days ) and a ' long-long ' ( 25 - 40 days ) protocol of GnRH-agonist administration for intracytoplasmic sperm injection . Group A consisted of 51 patients with a 15 - 24-day down regulation period and Group B consisted of 35 patients with a 25 - 40-day down regulation period , all of which entered ICSI due to severe male factor infertility . Duration and amount of gonadotropin stimulation , serum E2 on the day of hCG administration , number of oocytes retrieved , oocyte maturity , fertilization rate , cleavage rate and pregnancy outcome were comparable for the two groups of patients . Therefore , a flexible period of pituitary desensitization can be employed , allowing us to simplify planning for patients and for the medical staff without affecting the outcome of the trial Introduction The aim of the study was to compare the efficacy of half-dose , long-acting GnRH analogue ( Diphereline ) with Suprefact in IVF/ICSI ( in vitro fertilization/intracytoplasmic sperm injection ) cycles . Material and methods In this r and omized clinical trial performed in Royan Institute , 126 infertile women who were first time c and i date s for IVF/ICSI were enrolled . Patients were r and omly divided into two groups by using a r and om number table . In one group , 62 patients received a single half dose , 1.87 mg Diphereline , in mid-luteal phase . In the other group , 64 cases were treated with buserelin from the previous mid-luteal phase . P value less than 0.05 was considered significant . Results The mean age of patients in the Diphereline and Suprefact groups was 27.9 ±3.6 and 29.6 ±3.5 years , respectively ( p = 0.01 ) . In the Diphereline group , the mean number of used gonadotropins was 25.6 ±12.1 ampoules , while in the second group it was 25.9 ±8.5 ampoules . Numbers of retrieved and MII oocytes were significantly higher in the Diphereline group ( 12.1 ±6.3 and 9.6 ±5.5 ) in comparison to the Suprefact group ( 9.4 ±6.4 and 7.2 ±5.1 ) . Although the number of developed embryos in the Diphereline group was statistically higher than in the Suprefact group ( 6.1 ±3.9 vs. 4.7 ±3.4 , p = 0.04 ) there was no significant difference in pregnancy rate ( 37.1 % , 95 % CI [ 26.16 - 49.54 ] vs. 37.5 % , 95 % CI [ 26.67 - 49.75 ] ) . Conclusions A half-dose , long-acting GnRH agonist can be successfully used in ovarian stimulation and produces a higher number of MII oocytes and embryos . The pregnancy rates with this method are acceptable BACKGROUND The evidence underpinning the timing of an oocyte collection in IVF or ICSI is limited . The aim of this study was to assess the effect of the follicle diameter size of the dominant follicle on ongoing pregnancy rates . METHODS We conducted a r and omized controlled trial , including women aged between 18 and 43 years who were scheduled for GnRH agonist down-regulated IVF/ICSI treatment in four assisted conception units . Women were r and omized between timing oocyte collection when the leading follicle had a diameter of 22 mm or when the leading follicle had a diameter of 18 mm . The primary end-point was ongoing pregnancy , defined as a viable pregnancy at 12 weeks of gestation . RESULTS The trial had major problems with recruiting patients and after the planned 2 years of recruiting only half of the aim ed 400 inclusion s were obtained . We allocated 97 women to the 22-mm group and 93 women to the 18-mm group . In the 22-mm group more women reached an ongoing pregnancy ( 37 of 97 women , 38 % ) compared with the 18-mm group ( 22 of 93 women , 24 % ) result ing in a relative risk of 1.6 [ 95 % confidence interval ( CI ) : 1.03 - 2.5 ] . In a logistic regression analysis , the timing of oocyte collection , adjusted for female age , IVF/ICSI and centre , was still associated with ongoing pregnancy , although the association was no longer statistically significant ( OR : 2.0 ; 95 % CI : 0.96 - 4.2 ) CONCLUSIONS : This study suggests that delaying the timing of oocyte collection in IVF or ICSI results in better ongoing pregnancy rates , however , larger studies have to be performed to prove or refute these findings . TRIAL REGISTRATION IS RCT N24724622 BACKGROUND Partial pituitary desensitization using gonadotrophin-releasing hormone ( GnRH ) agonists may be sufficient in women undergoing controlled ovarian hyperstimulation for assisted reproduction . However , the minimal effective agonist dose remains to be determined . The aim of the study was to investigate the effect of a reduced daily dose of triptorelin , administered at the start of ovarian stimulation , on the results of IVF and intracytoplasmic sperm injection . METHODS A total of 132 patients was r and omized in two groups . Pituitary desensitization was obtained in group 1 ( 66 patients ) with a single 3.75 mg injection ( i.m . ) of triptorelin . In group 2 , 66 patients received 100 microg triptorelin daily , which was then reduced to 50 microg at the start of follicle-stimulating hormone ( FSH ) stimulation . RESULTS No significant differences were found in terms of pregnancy rate per transfer ( 38 % in group 1 versus 34.9 % in group 2 ) , implantation rate ( 20.2 versus 18 % ) and abortion rate ( 8.3 versus 9.1 % ) . The number of FSH ampoules used , as well as the number of days stimulation required , was significantly reduced in group 2 ( 41 + /- 26 versus 46.6 + /- 25.3 , P < 0.03 and 11 + /- 1.3 versus 11.8 + /- 1.5 , P < 0.002 respectively ) . No significant differences were seen in oestradiol concentrations and in follicle number , in the quantity of oocytes collected and fertilized , or in the number of embryos obtained or transferred . CONCLUSION A reduced dose of triptorelin is enough for pituitary suppression during ovarian stimulation but provides no significant improvement in IVF cycle outcome when compared with depot formulation . The possibility of a shorter treatment protocol requiring lower amounts of gonadotrophins should be considered in view of its economic advantage OBJECTIVE To compare the long and short protocol s of gonadotropin releasing hormone agonist ( GnRH-a ) administration for ovarian stimulation . SETTING University hospital . SUBJECTS 90 patients on their first attempt at in vitro fertilization and embryo transfer ( IVF-ET ) . METHOD The results of two stimulation protocol s were compared with respect to number of follicles greater than 17 mm , peak serum estradiol level , number of oocytes retrieved and fertilized , fertilization rate per oocyte , number of embryos transferred , and pregnancy rate per initiated cycle . RESULTS The number of follicles greater than 17 mm and the peak estradiol level were significantly ( P < .05 ) higher in the long protocol than those in the short protocol . The number of oocytes retrieved and fertilized , the number of embryos transferred , and the pregnancy rate per initiated cycle were also significantly ( P < .001 ) higher in the long protocol than those in the short protocol . The fertilization rates per oocyte retrieved did not differ significantly between groups . CONCLUSION The long protocol of gonadotropin releasing hormone agonist administration for ovarian stimulation in IVF-ET may be the preferred method when GnRH-a is used A r and omized prospect i ve study was undertaken to compare low and st and ard luteinizing hormone-releasing hormone agonist ( LHRHa ) dosage used in combination with gonadotrophins in ovarian stimulation for in-vitro fertilization ( IVF ) . A total of 42 ovulatory patients with mechanical infertility were administered 0.5 mg/day LHRHa ( Decapeptyl ) from day 21 of their cycles for 14 days . Following down-regulation , patients were r and omly allocated to continue with the same dose of LHRHa ( 22 patients , group A ) or to receive a lower dose of 0.1 mg/day LHRHa ( 20 patients , group B ) during folliculogenesis . Luteal phase was supported by daily i.m . progesterone ( 50 mg ) injections and human chorionic gonadotrophin ( HCG ; 1500 IU ) every 4 days . Ovarian response , human menopausal gonadotrophin ( HMG ) dosage used for induction of ovulation , evidence of premature luteinization , and clinical and laboratory IVF outcome , were compared between groups A and B. The two groups were comparable in respect of : age ( 32.6 + /- 0.7 and 33.0 + /- 0.9 years ) , HMG dosage ( 33.0 + /- 1.6 and 36.0 + /- 2.5 ampoules ) , day of HCG ( 11.2 + /- 0.3 and 12.2 + /- 0.4 ) , oocytes/patient ( 13.3 + /- 1.0 and 12.9 + /- 1.3 ) , fertilization rate ( 68.5 and 65.2 % ) , cleavage rate ( 95 % for both ) , pregnancy/embryo transfer ( 32 and 35 % ) and implantation rate ( 10.8 and 10.5 % ) , for groups A and B respectively . There was no evidence of premature luteinization or luteolysis in either group . It was concluded that lowering the dose of LHRHa to 0.1 mg/day during folliculogenesis had no adverse effect on ovarian response or clinical results . However , it had no advantage in reducing the HMG dose used for ovulation induction Background : Gonadotrophin-releasing hormone ( GnRH ) agonist is used for controlling ovarian stimulation in assisted reproductive technology ( ART ) cycles which has some benefits . Objective : To compare the efficacy of two different formulations of GnRH agonist : short-acting and long-acting , for ART protocol s. Material s and Methods : In a prospect i ve r and omized study , one hundred women who underwent ART cycles were r and omly divided into two groups . In group I , the patients received one single injection of 1.87 mg Triptorelin in previous mid-luteal phase . In group II , Decapeptyl 0.1 mg per day started from previous mid-luteal phase . Pregnancy outcome in in vitro fertilization ( IVF ) cycle was compared between two groups . Results : There were no statistically significant differences in the number of retrieved oocyte ( p=0.545 ) , fertilization ( p=0.876 ) , implantation ( p=0.716 ) and pregnancy rate ( p=0.727 ) between the two groups . Conclusion : There were not any advantages in IVF outcome between half-dose long-acting and short-acting GnRH agonist groups in ART cycle In a prospect i ve , controlled , r and omized study where two different agonists were used , we compared three different long desensitization protocol s for induction of multiple follicular growth in medically assisted conception cycles . In protocol A , 30 patients were injected with buserelin twice a day for 15 days prior to ovarian stimulation until human chorionic gonadotrophin ( HCG ) administration . In protocol B , 30 patients were injected with a single dose of long acting Triptorelin ( 3.75 mg ) 15 days before the ovarian stimulation onset . In protocol C , 30 patients were injected with the long acting Triptorelin 4 weeks before ovarian stimulation followed by daily administration of 0.1 mg of the same agonist until HCG injection . There was no difference in the ovarian response to exogenous gonadotrophin stimulation , except for the presence of premature luteinization in two patients in group B. A significantly higher number of mature oocytes was collected from patients with protocol A ; however , the fertilization and cleavage rate demonstrated no significant difference among the three groups of patients . The ongoing pregnancy rate and the implantation rate per treatment cycle were very similar in the three study groups . When the convenience , cost and side-effects for the patient are being considered , protocol B should be selected as the first choice when the agonist is utilized for the purpose of inducing pituitary desensitization before and during ovarian stimulation OBJECTIVE To compare the efficacy of two early cessation protocol s of triptorelin treatment in controlled ovarian hyperstimulation with the conventional long protocol in in vitro fertilization/intracytoplasmic sperm injection . DESIGN A double-blind , r and omized , multicenter study . SETTING Three Dutch hospitals . PATIENT(S ) One hundred seventy Output:	When long GnRHa protocol s and short GnRHa protocol s were compared , we found no conclusive evidence of a difference in live birth and ongoing pregnancy rates , but there was moderate quality evidence of higher clinical pregnancy rates in the long protocol group . None of the other analyses showed any evidence of a difference in birth or pregnancy outcomes between the protocol s compared . There was insufficient evidence to make any conclusions regarding adverse effects
MS22530	*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 Fifth Commission on Antiepileptic Drugs of the International League Against Epilepsy was asked to advise the ILAE Executive on the place of new drugs in the treatment of patients with newly diagnosed or chronic epilepsy . With the licensing of a significant number of new antiepileptic drugs ( AEDs ) in the last 5 - 10 years , there is an obvious need for these new treatments to be introduced efficiently and effectively to benefit the care and management of people with epilepsy . Implicit in this will be a determination of the comparative efficacy , tolerability , and overall effectiveness against st and ard ( existing ) AEDs and against other new drugs . Although many of the issues relating to comparative studies were addressed in Guidelines for the Clinical Evaluation of Antiepileptic Drugs , produced by the Fourth Commission , several complex ethical and method ological problems remain that would benefit from further discussion aim ed at the establishment of some form of consensus . Although determination of the relative risks of rare but potentially serious idiosyncratic adverse reactions and teratogenicity can be determined only by adequate postmarketing surveillance , other issues concerning the efficacy , tolerability , and effectiveness of new drugs can best be determined within the context of well- design ed r and omized ( or otherwise controlled ) clinical trials ( RCTs ) . It is the design , structure , and outcomes of such comparative RCTs that dem and further consideration . Many of the difficulties arise because the most meaningful and satisfactory comparative studies will essentially be those that compare monotherapy with a new agent with monotherapy with alternative agents . The Commission recognizes that several different parties have interests in comparative studies . First and foremost patients and their doctors require adequate information to guide daily practice in an “ evidence -based ” way so that patients can make fully informed decisions about their drug treatment . Individual pharmaceutical manufacturers need to know how their drug compares with other products so that a drug can be appropriately positioned in the market . Licensing authorities have traditionally ignored issues of comparative BACKGROUND Magnetic resonance (MR)-based T2 relaxation time measurement is a sensitive technique to detect neuropathological changes such as intramyelinic edema in vivo . OBJECTIVE To determine whether vigabatrin ( VGB ) causes an increase in T2 relaxation time in patients with newly diagnosed localization-related epilepsy over 1 year . METHODS Patients with newly diagnosed localization-related epilepsy who participated in a VGB-carbamazepine ( CBZ ) monotherapy trial were included . All were scanned on a 1.5 T Siemens SP63 Magnetom scanner . T2 maps of the brain were obtained at baseline and at follow-up 1 year later . Nine control subjects had repeated hippocampal T2 maps with a median interval of approximately 2 years . RESULTS 23 patients ( 12 on VGB and 11 on CBZ ) were included . There were no increased T2 relaxation times in the VGB treated group at follow-up and no significant differences between the two antiepileptic drug groups . There was a trend for the temporal and frontal white matter T2 relaxation times to be lower on follow-up in the patients compared to the control subjects . CONCLUSION The findings do not suggest that intramyelinic edema occurs in patients taking monotherapy VGB for 1 year At present , 34 patients aged 15 to 63 years with newly diagnosed epilepsy have been r and omly assigned to vigabatrin ( n = 17 ) or carbamazepine ( n = 17 ) . Evaluation of clinical data , neuropsychological assessment , quantitative spectral electroencephalogram ( EEG ) , and somatosensory- and visual-evoked potentials at baseline and after a 3 months ' maintenance phase are presented for 12 patients on vigabatrin and for 11 patients on carbamazepine . Among these patients , retention rate in the maintenance phase of the study is 75 % for vigabatrin patients ( two noncompliant patients and one nonresponder dropped out ) followed up for a mean of 11 months ( range , 5 to 16 months ) . The retention rate for carbamazepine is 100 % for the 11 patients , followed up for a mean of 9 months ( range , 3 to 17 months ) . Patients receiving vigabatrin showed significant improvements in sustained concentration and tasks requiring flexible mental processing after the 3-month maintenance period , compared to baseline . In the carbamazepine group , there was improvement only in delayed list recall , and in contrast , errors in visuomotor tasks requiring processing increased significantly . Patients on carbamazepine demonstrated slowed occipital mean frequencies , but vigabatrin treatment was not associated with any significant quantitative EEG changes . Significant prolongation of somatosensory-evoked potential N19 latencies was seen with both carbamazepine and vigabatrin . ( J Child Neurol 1991;6(Suppl):2S60 - 2S69 ) Carbamazepine ( CBZ ) is a drug of choice for the treatment of simple or complex partial seizures and secondary generalized seizures in adults and children . Vigabatrin ( VGB ) is a relatively new second line antiepileptic drug and was first registered for use in Pol and more than ten years ago . Few reports have been published on the comparison of efficacy of VGB in children with epilepsy . The objective of this study is to evaluate the safety , efficacy and EEG effects of initial VGB monotherapy compared with initial CBZ monotherapy in children with newly diagnosed epilepsy . We present results of a prospect i ve , outpatient and open study carried out in the University Hospital Center in Białystok . Twenty-six children with partial epilepsy treated with VGB and 28 patients treated with CBZ were studied . The evaluation of the efficacy of the two drugs did not reveal any significant differences . Very good ( reduction > 75 % ) seizure control was achieved in 22 out of 26 patients ( 84.6 % ) in the VGB group . One patient had a 50 - 75 % decrease of seizures ( good effect ) , similarly one child had a 25 - 50 % reduction of seizures ( mild effect ) . In two patients , we observed increased seizures ( myoclonic jerks ) . Very good seizure control was achieved in 17 out of 28 patients ( 60.7 % ) in the CBZ group . Good seizure control was achieved in 5 out of 28 patients ( 17.8 % ) and mild control was seen in two children . No improvement was observed in 4 ( 14 % ) of the patients . The EEG background activity was improved in VGB-treated patients . No effect on the EEG background activity was observed in CBZ-treated children . VGB seems to be a safe and effective antiepileptic drug as primary monotherapy for epilepsy in children with similar proportion of side effects as CBZ Reporting of adverse events ( AEs ) in r and omized clinical trials ( RCTs ) is often lacking and with limited application in the real world , as RCTs are of short duration , include small numbers of patients , and are selective for subjects lacking in comorbid conditions . It is not surprising that new and unexpected safety concerns emerge with any new drug after it has been launched and used by many more patients . Part of the problem is inherent to the way safety data are reported in RCTs . This article focuses on some of the shortcomings of AE reporting in RCTs , especially those involving tumor necrosis factor ( TNF ) inhibitors . Discussion focuses on reporting of " time-to-event " issues , use of st and ardized incidence ratios for comparison to normal population or disease controls , use of " patient-years " when reporting AEs , and the problem of adequate sample size and power calculations that are lacking in safety outcome data trials OBJECTIVE To evaluate the efficacy , safety , and cognitive effects of initial vigabatrin monotherapy compared with initial carbamazepine monotherapy in patients with newly diagnosed epilepsy . DESIGN Open , r and omized , controlled design . Follow-up period of 12 months . SETTING University hospital with an epilepsy center . PATIENTS A total of 100 patients , aged 15 to 64 years , classified as suffering from partial seizures and /or generalized tonic-clonic seizures were r and omized to either vigabatrin or carbamazepine monotherapy . Fifty-nine patients with a single epileptic seizure and no antiepileptic drug treatment served as a control population for objective safety measures . OUTCOME MEASURES To evaluate the comparative efficacy and toxicity of vigabatrin and carbamazepine , the drug success rate ( ie , the proportion of patients continuing successful treatment with the r and omly assigned drug ) after 12 months of steady-state treatment was used . To evaluate the safety of the drugs in addition to reported side effects , visual evoked potential recordings and neuropsychological evaluation were performed during follow-up . RESULTS During the 12-month follow-up period , 60 % of patients receiving vigabatrin and carbamazepine were treated successfully . Vigabatrin caused fewer side effects that required discontinuation of therapy . However , vigabatrin had to be discontinuated more often owing to lack of efficacy , and fewer of the successfully treated patients receiving vigabatrin achieved total freedom from seizures . Vigabatrin had no detrimental effects on cognitive functions . Retrieval from both episodic and semantic memory and flexibility of mental processing improved significantly in patients successfully treated with vigabatrin . CONCLUSION Vigabatrin seems to be an effective and safe antiepileptic drug as primary monotherapy for epilepsy with fewer cognitive side effects than carbamazepine PURPOSE The risk factors for visual field loss attributable to vigabatrin ( VAVFL ) are equivocal . This multinational , prospect i ve , observational study aim ed to clarify the principal/major factors for VAVFL . METHODS Interim analysis of three groups with refractory partial epilepsy , stratified by age ( 8 - 12 years ; > 12 years ) and exposure to vigabatrin ( VGB ) . Group I comprised participants treated with VGB for > or=6 months , Group II participants previously treated with VGB for > or=6 months who had discontinued the drug for > or=6 months and Group III those never treated with VGB . Perimetry was undertaken at least every six months , for up to 36 months ; results were evaluated masked to drug exposure . RESULTS Based upon 563 participants in the locked data set , 432 yielded one or more Conclusive visual field examinations . For Group I , the frequency of VAVFL at the last Conclusive examination was 10/32 ( 31.2 % ) for those aged 8 - 12 years and 52/125 ( 41.6 % ) for those aged > 12 years . For Group II , the proportions were 4/39 ( 10.3 % ) and 31/129 ( 24.0 % ) . No cases resembling VAVFL manifested in Group III . VAVFL was associated with duration of VGB therapy ( Odds ratio [ OR ] 14.2 ; 95 % CI 5.0 to 40.5 ) ; mean dose of VGB ( OR 8.5 ; 95 % CI 2.2 to 33.2 ) ; and male gender ( OR 2.1 ; 95 % CI 1.2 to 3.7 ) . VAVFL was more common with static than kinetic perimetry ( OR 2.3 , 95 % CI 1.3 to 4.2 ) . CONCLUSIONS The therapeutic benefit of VGB is counteracted by the progressive accrual of the risk of VAVFL with continued exposure and with increase in mean dose Vigabatrin is effective as add‐on therapy in about 50 % of patients with partial epilepsy refractory to drugs . Furthermore , at least half of the original responders maintain the response over several years . As monotherapy , both vigabatrin and carbamazepine seem to be successful in a similar proportion of newly diagnosed patients with epilepsy , but carbamazepine monotherapy fails more often due to side‐effects and vigabatrin more often due to lack of efficacy . However , vigabatrin monotherapy seems to be extremely well tolerated , particularly in relation to cognitive function The clinical efficacy and safety of vigabatrin ( VGB ) as add-on therapy for pharmaco-resistant focal epilepsies is well established . However , for an objective evaluation , the effects of the drug in the monotherapy of newly diagnosed subjects should be determined . With this aim , VGB was compared , in a r and omized , response conditional cross-over study , with carbamazepine ( CBZ ) , the most widely prescribed drug in focal epilepsies . Fifty-one patients with complex partial ( CP ) seizures were r and omly assigned to either the VGB or the CBZ group and evaluated after an initial 4 month period . The cross-over to the alternative drug was carried out , for an analogous period , only in cases with persisting seizures or in the presence of intolerable side effects . Patients who did not respond to either drug were subsequently treated with a combination of VGB and CBZ . No significant difference was revealed in the efficacies of VGB and CBZ ; a complete control of seizures was obtained in 17/37 patients ( 45.9 % ) treated with VGB and in 20/39 patients ( 51.3 % ) treated with CBZ . The side effects were somewhat more frequent ( 41 % ) and severe with CBZ than with VGB ( 21.6 % ) . The power to detect a 20 % difference between the two drugs was 75 % . The combination of the two drugs suppressed the seizures in 5 out of 14 resistant cases . The preliminary results in this small number of patients are encouraging and suggest that VGB may be considered as a first-line drug for epilepsy with CP seizures and as a valid alternative when other monotherapies are ineffective or poorly tolerated O Output:	No significant differences favoured VGB or CBZ in terms of time to treatment withdrawal and time to achieve six-month remission after dose stabilisation from r and omisation , but results did show a disadvantage for VGB on time to first seizure after r and omisation . Compared with CBZ , VGB was associated with more occurrences of weight gain and fewer occurrences of skin rash and drowsiness . No differences in visual field defects and visual disturbances were noted . Data are currently insufficient to address the risk-benefit balance of VGB versus CBZ monotherapy for epilepsy .
MS22531	*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 performed a prospect i ve , multicenter study to assess the tolerance and possible short-term effects of allergen vaccines administered according to a cluster schedule in the months immediately preceding the onset of the pollen season . The study was carried out in eight centers and included 191 patients ( children and adults ) with allergic respiratory disease due to sensitization to olive tree and /or grass pollen . Of these , 34 patients acted as controls and the remaining patients received immunotherapy administered in the initiation phase according to a cluster schedule of eight doses injected on four visits . After 3 months of treatment , significant differences were found between the two groups in medication consumption ( antihistamines in drops and oral formulations : p = 0.045 and p = 0.001 , respectively ; short-acting beta2-agonist treatments : p = 0.004 ) and respiratory symptoms ( wheezing and coughing : p = 0.035 and 0.014 , respectively ) . The cytokine profile ( interleukin [IL]-4 , 5 , 10 and 2 , interferon [ IFN-gamma ] , and tumor necrosis factor [ TNF-alpha ] ) was determined before the start of treatment and at the end of follow-up ( 4 - 5 months ) . Levels of IL-4 , 5 and 10 ( Th2 profile ) decreased while those of IL-2 , IFN-gamma , and TNF-alpha ( Th1 profile ) decreased . These differences were more marked in the active group than in the control group but were not statistically significant . No severe adverse effects were recorded . This study shows that the schedule tested had an acceptable tolerance profile and produced significant changes in symptom and medication scores after a few months of treatment . A double-blind , placebo-controlled study is needed to confirm these results BACKGROUND Sensitivity to Salsola kali is a frequent cause of allergic respiratory disease in various regions of Spain . However , there are very few articles in which this allergen has been studied . METHODS AND RESULTS In order to evaluate the tolerance of this extract , a prospect i ve study has been performed . This study was observational , multi-centred and open , involving 88 patients with allergic respiratory disease due to sensitivity to Salsola , aged between 5 and 52 years . The administration of the extract was performed subcutaneously , through one of two treatment schedules : cluster ( 8 doses in 4 visits ) or conventional ( 13 doses in 12 visits ) . A total of 42 adverse reactions were registered , in 26 patients ( 35 local reactions in 21 patients and 7 systemic reactions in 6 patients ) . Among the 7 systemic reactions , 4 were registered with the cluster protocol and 2 with the conventional protocol ( p = 0.329 ) . In no patients were serious adverse reactions registered . CONCLUSION The subcutaneous administration of a Salsola extract is safe and well tolerated , both when administered using a conventional schedule and when using a cluster schedule The st and ardisation of allergenic extracts in micrograms of the major allergen has encouraged the search for new treatment schedules , with the purpose of shortening the number of visits and doses required to reach the maintenance dose without eliciting a greater risk of adverse reactions for the patients . With this objective , a prospect i ve multicentre pharmacovigilance study was design ed that included 200 patient with allergic rhinoconjunctivitis and /or allergic asthma sensitised to mites ( Dermatophagoides pteronyssinu and /or farinae ) . The dose increment period was carried out using a cluster schedule , where the optimal dose wa reached after 4 visits , administering two doses in each visit . The duration of the study was 5 months and a total o 1902 doses were administered . At the end of the trial , 31 adverse reactions in 23 patients were recorded . Six of these were systemic ( 0.3 % of t administered doses ) recorded in 6 patients ( 3 % of the sample ) . One was an immediate reaction ( grade 1 ) and delayed ( 4 mild and 1 moderate ) . Two were asthmatic exacerbations , 2 cutaneous reactions , 1 rhinitis and 1 an unspecific symptom ( not IgE-mediated ) . Two appeared upon administration of the first vial and the remaining 4 after administration of the third cluster . Therefore , the schedule tested presents an adequate tolerance profile , suggesting savings ( compared to th conventional schedule of 13 doses per patient ) of 1800 visits and 1000 treatment doses in the whole study Twenty‐seven patients with allergy to house‐dust mite and the clinical symptoms of perennial rhinitis and /or mild asthma were treated with specific immunotherapy ( SIT ) with st and ardized extracts of house‐dust mite for 3 years . The success of therapy was evaluated in yearly intervals BACKGROUND Short-term immunotherapy ( STI ) can be beneficial for patients who are noncompliant with long-term specific immunotherapy . OBJECTIVE The efficacy and tolerance of STI with seven preseasonal injections of molecular st and ardized allergens from grass and rye pollen has been investigated in a double-blind , placebo-controlled multicenter study with 87 patients at 12 German University hospitals . METHODS Symptoms of the eyes , nose , and bronchi and use of symptomatic drugs were documented daily in diaries by patients with allergic rhinitis to grass and /or rye pollen and without bronchial asthma . Patients were monitored by skin prick test titration and measurement of levels of specific IgE and IgG4 . RESULTS The median nasal score for the 10 weeks with the strongest symptoms during the grass pollen season was significantly lower ( p = 0.014 ) with 35.0 for STI ( n = 41 ) versus 69.0 for placebo ( n = 40 ) ; the overall symptom score was 54.0 for STI versus 97.5 for placebo ( p = 0.020 ) . Only STI-treated patients exposed to less than 40 pollen grains per cubic meter per week showed a significantly lower nasal symptom score of 39.0 versus 75.0 for placebo ( p = 0.006 ) ; these patients also had fewer nasal symptoms and less use of topical nasal drugs ( p < 0.001 ) . The threshold dose in skin prick tests was significantly higher , being 9.06 histamine equivalent for skin prick test ( HEP ) for STI-treated patients who received the maximum dose ( n = 22 ) versus 4.33 HEP for placebo ( p = 0.005 ) . Specific IgE levels were significantly higher , being 55.9 SU/ml for STI versus 39.2 SU/ml for placebo after seven injections ( p = 0.006 ) and level of specific IgG4 was 5.36 % for STI versus 1.28 % for placebo ( p < 0.001 ) . No severe systemic reactions were observed . CONCLUSION STI with seven preseasonal injections with molecular st and ardized allergens is effective and well tolerated Background and Objectives : Allergy to house dust mite is one of the most common causes of allergic rhinitis ( AR ) in China . We sought to compare the efficacy and safety of a 6-week cluster schedule of specific immunotherapy with that of a 14-week conventional schedule for the treatment of subjects with persistent AR . Methods : The trial was a prospect i ve and r and omized study involving 96 patients with persistent AR , aged 14–60 years , who were allergic to Dermatophagoides pteronyssinus . While 48 patients were r and omly assigned to the cluster schedule reaching the maintenance dose within 6 weeks , the other 48 were r and omly assigned to the conventional schedule reaching the maintenance dose within 14 weeks . Eighty-nine patients completed a 1-year treatment course . While kinetic changes in clinical efficacy and adverse reactions were observed during the treatment , quality of life , cutaneous reactivity and serum-specific immunoglobulin E to Dermatophagoides pteronyssinus were measured before and after treatment . Results : The cluster schedule reduced the time to reach the maintenance dose by 57 % and caused mild systemic adverse reactions after 1.0 % of injections ( 6.7 % of patients ) , with no differences in comparison with the conventional schedule . Cluster specific immunotherapy led to decreases in clinical symptoms and earlier use of medication than did the conventional schedule . Similar improvements in quality of life and reduced cutaneous reactivity without significant changes in specific immunoglobulin E were observed in both groups after 1 year . Conclusions : The cluster schedule is a safe alternative to the conventional schedule with the advantage of achieving clinical effectiveness sooner Background : Four administration schedules of immunotherapy have been reported : conventional , cluster , rush and ultra-rush . Objectives : To evaluate the safety and the clinical advantage of using st and ardized modified allergen extracts in an ultra-rush protocol without premedication and /or hospitalization . Material and Methods : One thous and and sixty-eight patients with rhinoconjunctivitis and /or asthma sensitized to mites and /or pollen were included in a prospect i ve observational study . Patients received a therapeutic vaccine containing depigmented and glutaraldehyde-modified extracts ( mites and /or pollens ) adsorbed onto alum prescribed by a specialist . The schedule of administration consisted of injecting 0.2 and 0.3 ml of the vial of maximum concentration during the first day of immunotherapy , separated by a time interval of 30 min . All patients reached the maximum dose ( 0.5 ml ) after 2 injections . Tolerance was assessed by recording all side reactions related to immunotherapy , classified according to the criteria of the EAACI . Results : The total number of injections was 2,136 . All patients reached the maximum established dose on the 1st day . No premedication was used . Seven clinical ly relevant local reactions were recorded . The systemic reactions were 5 grade -1 ( 2 immediate and 3 delayed ) and 3 delayed grade -2 reactions . Conclusions : The therapeutic vaccines containing chemically modified extracts can be administered using an alternative ultra-rush schedule in an immunotherapy unit , reaching the maximum dose on the 1st day with 2 injections , without the need of premedication and /or hospitalization Background : Subcutaneous immunotherapy ( SCIT ) usually requires a long titration phase , which can be associated with various adverse events ( AEs ) . Objectives : It was the aim of this study to determine the safety of 2 cluster regimens for SCIT in patients with allergic rhinitis , with or without mild or moderate allergic asthma , who were sensitized to grass and /or tree pollen , or house dust mites ( HDM ) . Patients and Methods : Adult patients were included in a European , open-label , prospect i ve trial . Pollen-allergic patients received grass pollen , grass and olive pollen , or hazel , alder and birch pollen according to a 3-week titration cluster . HDM-allergic patients received HDM extract according to a 2-week titration cluster . The safety of the titration phase was assessed in terms of local and systemic AEs . Results : The safety analysis included 157 patients : 110 received pollen and 47 HDM extract . During the cluster titration , 248 AE episodes were reported in the pollen group and 113 in the HDM group ; these were mainly local reactions . Around one third of patients ( 30.9 % pollen and 38.3 % HDM ) did not experience any AE . In most cases ( 67.1 % of pollen and 71.1 % of HDM patients ) , AEs did not lead to a change in titration schedule . No anaphylactic reaction or other serious life-threatening systemic AEs were reported . Only 2 patients in the HDM group discontinued treatment because of AEs . Conclusions : Rapid cluster titration was well tolerated in adults with allergic rhinitis , with or without mild to moderate allergic asthma , due to pollen or HDM . This short-titration , high-dose cluster regime may allow better patient compliance and cost savings BACKGROUND Specific immunotherapy ( SIT ) represents the only specific treatment that can be offered to allergic patients apart from allergen avoidance . SIT has been widely used in pollen allergic rhinitis . Clinical efficacy has been demonstrated in several controlled clinical trials and depends on the specific allergen the individual patient is sensitive to , the quality and total amount of allergen applied , and the SIT schedule . In classic SIT , gradually increasing dosages of the allergen extract are injected subcutaneously . Several dosage schedules for subcutaneous SIT can be applied . In Cluster-SIT , 2 - 3 injections per day of treatment are given once a week during induction treatment . PATIENTS In this study , we investigated 64 patients ( 33 female , 31 male ) from 18 to 54 years ( 26.9 + /- 5.1 years ) in terms of side-effects of Cluster-SIT during induction treatment . RESULTS The total amount of enlarged local reactions ( > grade 1 ) was n = 77 or 15.2 % of all injections . Of these , 68 ( 88 % ) were classified as immediate reactions , 8 ( 11 % ) were late phase reactions and 1 ( 1 % ) was immediate as well as late phase reaction . Of all enlarged local reactions , 48 ( 62 % ) were grade 1 reactions , 13 ( 17 % ) were grade 2 reactions , 13 ( 17 % ) were grade 3 reactions and 1 ( 1 % ) was a grade 4 reaction . The total amount Output:	Our meta- analysis showed that cluster SCIT have similar effect in reduction of both rhinitis symptoms and the requirement for anti-allergic medication compared with conventional SCIT , but when comparing cluster SCIT with placebo , no statistic significance were found in reduction of symptom scores or medication scores . Based on the current limited evidence , we still could not conclude affirmatively that cluster SCIT was a safe and efficacious option for the treatment of AR patients .
MS22532	*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 the present study was to evaluate the effects of a school-based , 2-year , multi-component intervention on BMI , eating and physical activity behaviour in Fl and ers , Belgium , targeting children aged 3 - 6 years in communities of high and low socio-economic status ( SES ) . DESIGN Cluster-r and omized controlled trial . SETTING Thirty-one pre- primary and primary schools in three different intervention communities and three paired-matched ( on SES profile ) control communities in Fl and ers , Belgium . SUBJECTS BMI Z-scores at baseline and follow-up were calculated for 1102 children . Question naires with sociodemographic data and FFQ were available from 694 of these 1102 children . RESULTS No significant effects were found on BMI Z-scores for the total sample . However , there was a significant decrease in BMI Z-score of 0·11 in the low-SES intervention community compared with the low-SES control community , where the BMI Z-score increased by 0·04 ( F = 6·26 , P = 0·01 ) . No significant intervention effects could be found for eating behaviour , physical activity or screen-time . There were no significant interaction effects of age and gender of the children on the outcome variables . CONCLUSIONS Although no significant effects were found for BMI Z-scores in the total sample , this intervention had a promising effect in the low-SES community of reducing excess weight gain among young children OBJECTIVE To evaluate the impact of nutrition education in kindergartens and to promote healthy dietary habits in children . DESIGN Prospect i ve cohort study . Four kindergartens with 1252 children were r and omized to the intervention group and three with 850 children to the control group . The personal nutritional knowledge , attitudes and dietary behaviours of the parents were also investigated . Each month , children and parents in the intervention group participated in nutrition education activities . The main outcome measures were anthropometrics and diet-related behaviours of the children and the nutritional knowledge and attitudes of the parents at baseline , 6 months ( mid-term ) and 1 year ( post-test ) . Baseline demographic and socio-economic characteristics were also collected . SETTING Seven kindergartens from Hefei , the capital city of Anhui Province , eastern China . SUBJECTS Two thous and one hundred and two 4- to 6-year-old pre-schoolers from seven kindergartens participated . RESULTS The prevalence of children 's unhealthy diet-related behaviours decreased significantly and good lifestyle behaviours increased in the group receiving nutrition education compared with controls . Parental eating habits and attitudes to planning their children 's diets also changed appreciably in the intervention group compared with the control group ( P < 0.05 ) . However , there were no statistically significant differences in children 's height , weight , height-for-age Z-score or weight-for-age Z-score between the two groups . CONCLUSIONS Kindergarten-based nutrition education improves pre-schoolers ' lifestyle behaviours and brings about beneficial changes in parents ' attitudes to planning their children 's diets and their own personal eating habits BACKGROUND School programs can be effective in modifying knowledge , attitudes , and habits relevant to long-term risk of chronic diseases associated with sedentary lifestyles . As part of a long-term research strategy , we conducted an educational intervention in preschool facilities to assess changes in preschoolers ' knowledge , attitudes , and habits toward healthy eating and living an active lifestyle . METHODS Using a cluster design , we r and omly assigned 14 preschool facilities in Bogotá , Colombia to a 5-month educational and playful intervention ( 7 preschool facilities ) or to usual curriculum ( 7 preschool facilities ) . A total of 1216 children aged 3 - 5 years , 928 parents , and 120 teachers participated . A structured survey was used at baseline , at the end of the study , and 12 months later to evaluate changes in knowledge , attitudes , and habits . RESULTS Children in the intervention group showed a 10.9 % increase in weighted score , compared with 5.3 % in controls . The absolute adjusted difference was 3.90 units ( 95 % confidence interval [ CI ] , 1.64 - 6.16 ; P < .001 ) . Among parents , the equivalent statistics were 8.9 % and 3.1 % , respectively ( absolute difference 4.08 units ; 95 % CI , 2.03 to 6.12 ; P < .001 ) , and among teachers , 9.4 % and 2.5 % , respectively ( absolute difference 5.36 units ; 95 % CI , -0.29 - 11.01 ; P = .06 ) . In the intervened cohort 1 year after the intervention , children still showed a significant increase in weighted score ( absolute difference of 6.38 units ; P < .001 ) . CONCLUSIONS A preschool-based intervention aim ed at improving knowledge , attitudes , and habits related to healthy diet and active lifestyle is feasible , efficacious , and sustainable in very young children Background The onset of inadequate behaviors leading to the development of risk factors for chronic diseases is known to occur early in life . An effective program for health promotion should therefore focus on children and their environment , as the starting point for behavior development . The overarching objective of the Program SI ! ( Salud Integral - Comprehensive Health ) is to intervene at the school level , to establish and develop life-lasting habits that will help preserving health during adulthood . The Program SI ! comprises five consecutive subprograms according to the five stages of education in Spain , the first being in preschoolers . This study aims to evaluate the efficacy of Program SI ! to establish and improve lifestyle behaviors in children ( preschoolers aged 3–5 years ) , their parents , and teachers , and also improving the school environment . A secondary objective is to evaluate improvements in cardiovascular health-related markers ( anthropometric parameters , blood pressure , and dietary and physical activity patterns ) in these same children . Methods / design 24 public schools from the city of Madrid ( Spain ) were allocated through stratified r and omization to intervention or control . The intervention schools follow the Program SI ! , which provides didactic units , emotions cards , healthy tips , and online re sources . The intervention schools integrate the Program SI ! into their scholar curriculum organized in four complete weeks during each academic year during the 3 years of preschool education . Control schools follow their normal curriculum . Primary outcomes are 1-year , and 3-year changes from baseline of scores for knowledge , attitudes , and habits ( KAH ) of children , their parents and teachers in regards to a healthy lifestyle . Secondary outcomes are 1-year , and 3-year changes from baseline in clinical and anthropometric parameters of children . Discussion The Program SI ! is a long-term health promotion program starting in 3 years old . It incorporates the traditional areas of intervention ( diet and physical activity ) , introducing additional components such as knowledge of the human body and management of emotions to achieve a comprehensive intervention . The Program SI ! is design ed to be an effective , sustainable health promotion program for the adoption of healthy behaviors from early in life . Trial registration Trial registration number : OBJECTIVE To determine the impact of an implementation intervention design ed to introduce policies and practice s supportive of healthy eating in centre-based child-care services . Intervention strategies included staff training , re sources , incentives , follow-up support , and performance monitoring and feedback . DESIGN A quasi-experimental design was used to assess change over 20 months in healthy eating policy and practice in intervention and comparison child-care services . SETTING The Hunter New Engl and ( HNE ) region of New South Wales ( NSW ) , Australia . SUBJECTS All centre-based child-care services ( n 287 ) in the intervention region ( HNE ) were invited and 240 ( 91 % response rate ) participated . Two hundred and ninety-six services in the rest of NSW were r and omly selected as a comparison region and 191 participated ( 76 % response rate ) . A sub- analysis was conducted on those services that provided children food ( n 196 at baseline and n 190 at follow-up ) . Ninety-six provided menus for analysis at baseline ( HNE , n 36 ; NSW , n 50 ) and 102 provided menus at follow-up ( HNE , n 50 ; NSW , n 52 ) . RESULTS Services in the intervention region were significantly more likely to provide only plain milk and water for children ( P = 0.018 ) and to engage parents in nutrition policy or programmes ( P = 0.002 ) . They were also more likely ( P = 0.056 ) to have nutrition policy on home packed food . In addition , menus of services that provided lunch were significantly more likely to comply with healthy eating guidelines for sweetened drinks ( P < 0.001 ) , fruit ( P < 0.001 ) and vegetables ( P = 0.01 ) . CONCLUSIONS An implementation intervention was able to modify policy and practice in a large number of child-care services so that they were more supportive of healthy eating Objective To test the effect of a multidimensional lifestyle intervention on aerobic fitness and adiposity in predominantly migrant preschool children . Design Cluster r and omised controlled single blinded trial ( Ballabeina study ) over one school year ; r and omisation was performed after stratification for linguistic region . Setting 40 preschool classes in areas with a high migrant population in the German and French speaking regions of Switzerl and . Participants 652 of the 727 preschool children had informed consent and were present for baseline measures ( mean age 5.1 years ( SD 0.7 ) , 72 % migrants of multicultural origins ) . No children withdrew , but 26 moved away . Intervention The multidimensional culturally tailored lifestyle intervention included a physical activity programme , lessons on nutrition , media use ( use of television and computers ) , and sleep and adaptation of the built environment of the preschool class . It lasted from August 2008 to June 2009 . Main outcome measures Primary outcomes were aerobic fitness ( 20 m shuttle run test ) and body mass index ( BMI ) . Secondary outcomes included motor agility , balance , percentage body fat , waist circumference , physical activity , eating habits , media use , sleep , psychological health , and cognitive abilities . Results Compared with controls , children in the intervention group had an increase in aerobic fitness at the end of the intervention ( adjusted mean difference : 0.32 stages ( 95 % confidence interval 0.07 to 0.57 ; P=0.01 ) but no difference in BMI ( −0.07 kg/m2 , −0.19 to 0.06 ; P=0.31 ) . Relative to controls , children in the intervention group had beneficial effects in motor agility ( −0.54 s , −0.90 to −0.17 ; P=0.004 ) , percentage body fat ( −1.1 % , −2.0 to −0.2 ; P=0.02 ) , and waist circumference ( −1.0 cm , −1.6 to −0.4 ; P=0.001 ) . There were also significant benefits in the intervention group in reported physical activity , media use , and eating habits , but not in the remaining secondary outcomes . Conclusions A multidimensional intervention increased aerobic fitness and reduced body fat but not BMI in predominantly migrant preschool children . Trial registration Clinical Trials NCT00674544 The preschool years offer an opportunity to interrupt the trajectory toward obesity in black children . The Hip-Hop to Health Jr. Obesity Prevention Effectiveness Trial was a group-r and omized controlled trial assessing the feasibility and effectiveness of a teacher-delivered weight control intervention for black preschool children . The 618 participating children were enrolled in 18 schools administered by the Chicago Public Schools . Children enrolled in the nine schools r and omized to the intervention group received a 14-week weight control intervention delivered by their classroom teachers . Children in the nine control schools received a general health intervention . Height and weight , physical activity , screen time , and diet data were collected at baseline and postintervention . At postintervention , children in the intervention schools engaged in more moderate-to-vigorous physical activity ( MVPA ) than children in the control schools ( difference between adjusted group means = 7.46 min/day , P = 0.02 ) . Also , children in the intervention group had less total screen time ( -27.8 min/day , P = 0.05 ) . There were no significant differences in BMI , BMI Z score , or dietary intake . It is feasible to adapt an obesity prevention program to be taught by classroom teachers . The intervention showed positive influences on physical activity and screen time , but not on diet . Measuring diet and physical activity in preschool children remains a challenge , and interventions delivered by classroom teachers require both intensive initial training and ongoing individualized supervision Dietary patterns are useful in nutritional epidemiology , providing a comprehensive alternative to the traditional approach based on single nutrients . The Cardiovascular Risk in Young Finns Study is a prospect i ve cohort study with a 21-year follow-up . At baseline , detailed quantitative information on subjects ' food consumption was obtained using a 48 h dietary recall method ( n 1768 , aged 3 - 18 years ) . The interviews were repeated after 6 and 21 years ( n 1200 and n 1037 , respectively ) . We conducted a principal component analysis to identify major dietary patterns at each study point . A set of two similar patterns was recognised throughout the study . Pattern 1 was positively correlated with consumption of traditional Finnish foods , such as rye , potatoes , milk , butter , sausages and coffee , and negatively correlated with fruit , berries and dairy products other than Output:	Children 's dietary food intake and food choices were significantly influenced . Interventions to prevent obesity did not significantly change children 's anthropometric measures or had mixed results . Evidence was more convincing if interventions were multi-component , addressed physical activity and diet , targeted individual-level and environmental-level determinants and engaged parents . Positive outcomes were mostly facilitated by research ers/external experts and these results were not replicated when implemented in centres by ECEC providers without this support .
MS22533	*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 pilot study examined the effects of a teacher-taught , locomotor skill (LMS)-based physical activity ( PA ) program on the LMS and PA levels of minority preschooler-aged children . Eight low-socioeconomic status preschool classrooms were r and omized into LMS-PA ( LMS-oriented lesson plans ) or control group ( supervised free playtime ) . Interventions were delivered for 30 min/day , five days/week for six months . Changes in PA ( accelerometer ) and LMS variables were assessed with MANCOVA . LMS-PA group exhibited a significant reduction in during-preschool ( F ( 1,16 ) = 6.34 , p = .02 , d = 0.02 ) and total daily ( F ( 1,16 ) = 9.78 , p = .01 , d = 0.30 ) percent time spent in sedentary activity . LMS-PA group also exhibited significant improvement in leaping skills , F ( 1 , 51 ) = 7.18 , p = .01 , d = 0.80 ) . No other , significant changes were observed . The implementation of a teacher-taught , LMS-based PA program could potentially improve LMS and reduce sedentary time of minority preschoolers Objective To assess the effect of a governmentally-led center based child care physical activity program ( Youp’là Bouge ) on child motor skills . Patients and methods We conducted a single blinded cluster r and omized controlled trial in 58 Swiss child care centers . Centers were r and omly selected and 1:1 assigned to a control or intervention group . The intervention lasted from September 2009 to June 2010 and included training of the educators , adaptation of the child care built environment , parental involvement and daily physical activity . Motor skill was the primary outcome and body mass index ( BMI ) , physical activity and quality of life secondary outcomes . The intervention implementation was also assessed . Results At baseline , 648 children present on the motor test day were included ( age 3.3 ± 0.6 , BMI 16.3 ± 1.3 kg/m2 , 13.2 % overweight , 49 % girls ) and 313 received the intervention . Relative to children in the control group ( n = 201 ) , children in the intervention group ( n = 187 ) showed no significant increase in motor skills ( delta of mean change ( 95 % confidence interval : -0.2 ( −0.8 to 0.3 ) , p = 0.43 ) or in any of the secondary outcomes . Not all child care centers implemented all the intervention components . Within the intervention group , several predictors were positively associated with trial outcomes : 1 ) free-access to a movement space and parental information session for motor skills 2 ) highly motivated and trained educators for BMI 3 ) free-access to a movement space and purchase of mobile equipment for physical activity ( all p < 0.05 ) . Conclusion This “ real-life ” physical activity program in child care centers confirms the complexity of implementing an intervention outside a study setting and identified potentially relevant predictors that could improve future programs . Trial registration Clinical trials.gov OBJECTIVES The aims were to examine the relationship between children 's motor skill levels and types of physical activities performed during preschool attendance , and to examine the relationship between motor skill performance and parent perception of athletic competence . DESIGN Cross-sectional . METHODS Participants were 264 , 3- , 4- , and 5-year-old children from 22 preschools . Locomotor and object control skills were assessed with a st and ardized motor skill protocol . Direct observation ( OSRAC-P ) was used to record activity types : walk , run , jump/skip , dance , and throw . Parents rated their child 's athletic competence . Children were categorized into tertiles for locomotor and object control scores . Mixed models were used to test for differences across motor skill tertiles for each aim . Models controlled for sex , age , race/ethnicity , body mass index , and parent education , with preschool as a r and om variable . RESULTS Children in the highest locomotor tertile engaged in more dancing than children in the lowest tertile ( p = 0.04 ) . Children in the highest object control tertile engaged in throwing more frequently than children in lower tertiles ( p < 0.05 ) . Parents of children in the highest locomotor tertile perceived their children 's competence as higher than parents of children in lower tertiles ( p < 0.05 ) . Parents of children in the lowest object control tertile perceived their children 's competence as significantly lower than parents of children in higher tertiles ( p < 0.05 ) . CONCLUSIONS These findings point to the need for policy and practice research to help parents and child care professionals provide opportunities for young children to learn and practice motor skills The aim of this study was to assess the feasibility , acceptability and potential efficacy of a physical activity program for preschool children . A 20-week , 2-arm parallel cluster r and omized controlled pilot trial was conducted . The intervention comprised structured activities for children and professional development for staff . The control group participated in usual care activities , which included design ated inside and outside playtime . Primary outcomes were movement skill development and objective ly measured physical activity . At follow-up , compared with children in the control group , children in the intervention group showed greater improvements in movement skill proficiency , with this improvement statically significant for overall movement skill development ( adjust diff . = 2.08 , 95 % CI 0.76 , 3.40 ; Cohen 's d = 0.47 ) and significantly greater increases in objective ly measured physical activity ( counts per minute ) during the preschool day ( adjust diff . = 110.5 , 95 % CI 33.6 , 187.3 ; Cohen 's d = 0.46 ) . This study demonstrates that a physical activity program implemented by staff within a preschool setting is feasible , acceptable and potentially efficacious Differences in the age of attainment of motor skills between boys and girls have been established in previous studies . It has been noted that boys develop ball skills earlier than girls and that girls acquire manual dexterity before boys . The purpose of this study was to determine if the same differences could be identified in a group of typically developing seven and eight year old children using the Movement Assessment Battery for Children Test ( MABC Test ) . In this study , a physiotherapist administered the MABC Test to 103 r and omly selected children ( boys-60 , girls-43 ) . The MABC Test examines children 's motor skills in the areas of manual dexterity , ball skills and balance . Results were analyzed using analysis of variance ( ANOVA ) . The ANOVA results indicated significant differences between boys ' and girls ' ball skill scores and manual dexterity scores PURPOSE To test for relationships between objective ly measured habitual physical activity and fundamental movement skills in a relatively large and representative sample of preschool children . METHODS Physical activity was measured over 6 d using the Computer Science and Applications ( CSA ) accelerometer in 394 boys and girls ( mean age 4.2 , SD 0.5 yr ) . Children were scored on 15 fundamental movement skills , based on the Movement Assessment Battery , by a single observer . RESULTS Total physical activity ( r=0.10 , P<0.05 ) and percent time spent in moderate to vigorous physical activity ( MVPA ) ( r=0.18 , P<0.001 ) were significantly correlated with total movement skills score . Time spent in light-intensity physical activity was not significantly correlated with motor skills score ( r=0.02 , P>0.05 ) . CONCLUSIONS In this sample and setting , fundamental movement skills were significantly associated with habitual physical activity , but the association between the two variables was weak . The present study questions whether the widely assumed relationships between motor skills and habitual physical activity actually exist in young children UNLABELLED The aim of this study was to examine the relationship between motor proficiency and pedometer-determined physical activity in 5 - 6 year-old children . Participants ( n = 232 ) were r and omly recruited and assessed from 30 kindergartens in Northern Greece . Two trained research ers administered the measurements for the assessment of children 's motor proficiency by using the BOTMP-SF . Physical activity was assessed by OMRON pedometers . Significant relationships between BOTMP-SF st and ard score and steps ( S ) , aerobic walking time ( AWT ) and aerobic steps ( AS ) , ( p < .05 ) were found . When motor proficiency was divided into quartiles to assess the distribution of the relationship between motor proficiency and pedometer-derived variables , significant associations were found for AWT , S and AS ( p < .001 ) . Young children with high levels of motor proficiency were more active in contrast to their peers with lower motor proficiency . The findings add to the growing body of literature that considers motor skills/abilities as important elements of physical activity participation . ( ABBREVIATIONS S-steps per day ; AS-aerobic steps per day ; AWT-aerobic walking time ( minutes·day(-1 ) ) ; BOTMP-SF-Bruininks-Oseretsky Test of Motor Proficiency-Short Form ( st and ard score ) ) Output:	Conclusions An association has been consistently documented between motor skill competence and physical activity .
MS22534	*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 CARDS trial , a multicentre , r and omized , controlled trial , found that atorvastatin 10 mg/day for patients with type 2 diabetes mellitus and normal low-density lipoprotein (LDL)-cholesterol significantly reduced cardiovascular ( CV ) events , including stroke . We estimated the cost effectiveness of atorvastatin as primary prevention against CV disease from the short-term and lifetime US payer perspectives . Research design and methods We constructed a decision analytic ( Markov ) model to evaluate long-term costs and outcomes for atorvastatin 10 mg/day versus no HMG-CoA reductase inhibitor ( statin ) therapy for patients with type 2 diabetes and no history of a CV event . CV event rates and survival were based on risk equations calibrated to CARDS and applied to a US type 2 diabetes population ; the atorvastatin effect on CV events was based on hazard ratios from CARDS ; direct medical care costs were based on US treatment patterns and published costs analyses of patients with diabetes . Costs were valued in $ US , year 2005 values ; costs and benefits were discounted at 3 % per annum . Results Within the time horizon of the trial ( 5 years ) , the cost effectiveness of atorvastatin was $ US137 276 per QALY . At 10 years , the incremental cost per QALY improved to $ US3640 per QALY . At 25 years , overall costs were lower and QALYs higher in the atorvastatin arm . Costs of managing CV events were lower after 5 years for patients treated with atorvastatin . Conclusions For patients with type 2 diabetes and one additional risk factor for CV disease , normal LDL-cholesterol and no history of a CV event , primary prevention with atorvastatin appears to be cost saving and improve outcomes over 25 years , although it is costly from a short-term US payer perspective . From both a medical and an economic viewpoint , primary prevention is desirable in this patient population BACKGROUND The objective of this study was to assess the cost-effectiveness of pravastatin therapy in survivors of myocardial infa rct ion with average cholesterol levels . METHODS We performed a cost-effectiveness analysis based on actual clinical , cost , and health-related quality -of-life data from the Cholesterol and Recurrent Events ( CARE ) trial . Survival and recurrent coronary heart disease events were modeled from trial data in Markov models , with the use of different assumptions regarding the long-term benefit of therapy . RESULTS Pravastatin therapy increased quality -adjusted life expectancy at an incremental cost of $ 16,000 to $ 32,000 per quality -adjusted life-year gained . In subgroup analyses , the cost-effectiveness of pravastatin therapy was more favorable for patients > 60 years of age and for patients with pretreatment low-density lipoprotein cholesterol levels > 125 mg/dL. Results were sensitive to the cost of pravastatin and to assumptions about long-term survival benefits from pravastatin therapy . CONCLUSIONS The cost-effectiveness of pravastatin therapy in survivors of myocardial infa rct ion with average cholesterol levels compares favorably with other interventions Background Simvastatin , 20 mg , plus ezetimibe , 10 mg , daily ( simvastatin plus ezetimibe ) reduced major atherosclerotic events in patients with moderate to severe chronic kidney disease ( CKD ) in the Study of Heart and Renal Protection ( SHARP ) , but its cost-effectiveness is unknown . Study Design Cost-effectiveness of simvastatin plus ezetimibe in SHARP , a r and omized controlled trial . Setting & Population 9,270 patients with CKD r and omly assigned to simvastatin plus ezetimibe versus placebo ; participants in categories by 5-year cardiovascular risk ( low , < 10 % ; medium , 10%-<20 % ; or high , ≥20 % ) and CKD stage ( 3 , 4 , 5 not on dialysis , or on dialysis therapy ) . Model , Perspective , & Timeline Assessment during SHARP follow-up from the UK perspective ; long-term projections . Intervention Simvastatin plus ezetimibe ( 2015 UK £ 1.19 per day ) during 4.9 years ’ median follow-up in SHARP ; scenario analyses with high-intensity statin regimens ( 2015 UK £ 0.05-£1.06 per day ) . Outcomes Additional health care costs per major atherosclerotic event avoided and per quality -adjusted life-year ( QALY ) gained . Results In SHARP , the proportional reductions per 1 mmol/L of low-density lipoprotein ( LDL ) cholesterol reduction with simvastatin plus ezetimibe in all major atherosclerotic events of 20 % ( 95 % CI , 6%-32 % ) and in the costs of vascular hospital episodes of 17 % ( 95 % CI , 4%-28 % ) were similar across participant categories by cardiovascular risk and CKD stage . The 5-year reduction in major atherosclerotic events per 1,000 participants ranged from 10 in low-risk to 58 in high-risk patients and from 28 in CKD stage 3 to 36 in patients on dialysis therapy . The net cost per major atherosclerotic event avoided with simvastatin plus ezetimibe compared to no LDL-lowering regimen ranged from £ 157,060 in patients at low risk to £ 15,230 in those at high risk ( £ 30,500-£39,600 per QALY ) ; and from £ 47,280 in CKD stage 3 to £ 28,180 in patients on dialysis therapy ( £ 13,000-£43,300 per QALY ) . In scenario analyses , generic high-intensity statin regimens were estimated to yield similar benefits at substantially lower cost . Limitations High-intensity statin-alone regimens were not studied in SHARP . Conclusions Simvastatin plus ezetimibe prevented atherosclerotic events in SHARP , but other less costly statin regimens are likely to be more cost-effective for reducing cardiovascular risk in CKD OBJECTIVE To evaluate the incremental cost-effectiveness ratio ( ICER ) of switching to ezetimibe/simvastatin ( Eze/Simva ) compared with doubling the submaximal statin doses , in patients with acute coronary syndrome ( ACS ) events in the INFORCE study . METHODS Lifetime treatment costs and benefits were computed using a Markov model . Model inputs included each patient 's cardiovascular risk factor profile and actual lipid values at baseline and 12 weeks ( endpoint ) . Cardiovascular event and drug costs were discounted at 3.5 % . Age-specific utilities were based on UK literature values and non-coronary heart disease mortality rates on the Office of National Statistics data . In the INFORCE study , 384 patients taking statins at stable doses for ≥6 weeks before hospital admission were stratified by statin dose/potency ( low , medium , and high ) and then r and omized to doubling the statin dose or switching to Eze/Simva 10/40 mg for 12 weeks . RESULTS The Eze/Simva group ( n=195 ) had a higher mean baseline total cholesterol than the double-statin group ( n=189 ) . Analyses were adjusted for baseline characteristics . In the INFORCE study , Eze/Simva reduced low-density lipoprotein cholesterol ( LDL-C ) by ∼30 % ( vs. 4 % with doubling statin doses ) and significantly enhanced LDL-C goal attainment . In the cost-effectiveness analysis , Eze/Simva conferred 0.218 incremental discounted quality -adjusted life year ( QALY ) at a discounted incremental cost of £ 2524 , for an ICER of £ 11,571/QALY ( 95 % confidence interval=£8181-£18,600/QALY ) . The ICER was £ 13,552/QALY , £ 11,930/QALY , and £ 10,148/QALY in the low- , medium- , and high-potency strata , respectively . CONCLUSIONS Switching to Eze/Simva 10/40 mg is projected to be a cost-effective treatment ( vs. double-statin ) in UK patients with ACS OBJECTIVES Mathematical modeling is used widely in economic evaluations of pharmaceuticals and other health-care technologies . Users of models in government and the private sector need to be able to evaluate the quality of models according to scientific criteria of good practice . This report describes the consensus of a task force convened to provide modelers with guidelines for conducting and reporting modeling studies . METHODS The task force was appointed with the advice and consent of the Board of Directors of ISPOR . Members were experienced developers or users of models , worked in academia and industry , and came from several countries in North America and Europe . The task force met on three occasions , conducted frequent correspondence and exchanges of drafts by electronic mail , and solicited comments on three drafts from a core group of external review ers and more broadly from the membership of ISPOR . RESULTS Criteria for assessing the quality of models fell into three areas : model structure , data used as inputs to models , and model validation . Several major themes cut across these areas . Models and their results should be represented as aids to decision making , not as statements of scientific fact ; therefore , it is inappropriate to dem and that models be vali date d prospect ively before use . However , model assumptions regarding causal structure and parameter estimates should be continually assessed against data , and models should be revised accordingly . Structural assumptions and parameter estimates should be reported clearly and explicitly , and opportunities for users to appreciate the conditional relationship between inputs and outputs should be provided through sensitivity analyses . CONCLUSIONS Model-based evaluations are a valuable re source for health-care decision makers . It is the responsibility of model developers to conduct modeling studies according to the best practicable st and ards of quality and to communicate results with adequate disclosure of assumptions and with the caveat that conclusions are conditional upon the assumptions and data on which the model is built OBJECTIVE To measure the cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with established ischaemic heart disease and average baseline cholesterol levels . DESIGN Prospect i ve economic evaluation within a double-blind r and omised trial ( Long-Term Intervention with Pravastatin in Ischaemic Disease [ LIPID ] ) , in which patients with a history of unstable angina or previous myocardial infa rct ion were r and omised to receive 40 mg of pravastatin daily or matching placebo . PATIENTS AND SETTING 9014 patients aged 35 - 75 years from 85 centres in Australia and New Zeal and , recruited from June 1990 to December 1992 . MAIN OUTCOME MEASURES Cost per death averted , cost per life-year gained , and cost per quality -adjusted life-year gained , calculated from measures of hospitalisations , medication use , outpatient visits , and quality of life . RESULTS The LIPID trial showed a 22 % relative reduction in all-cause mortality ( P < 0.001 ) . Over a mean follow-up of 6 years , hospital admissions for coronary heart disease and coronary revascularisation were reduced by about 20 % . Over this period , pravastatin cost $ A4913 per patient , but reduced total hospitalisation costs by $ A1385 per patient and other long-term medication costs by $ A360 per patient . In a sub sample of patients , average quality of life was 0.98 ( where 0 = dead and 1 = normal good health ) ; the treatment groups were not significantly different . The absolute reduction in all-cause mortality was 3.0 % ( 95 % CI , 1.6%-4.4 % ) , and the incremental cost was $ 3246 per patient , result ing in a cost per life saved of $ 107 730 ( 95 % CI , $ 68 626-$209 881 ) within the study period . Extrapolating long-term survival from the placebo group , the undiscounted cost per life-year saved was $ 7695 ( and $ 10 938 with costs and life-years discounted at an annual rate of 5 % ) . CONCLUSIONS Pravastatin therapy for patients with a history of myocardial infa rct ion or unstable angina and average cholesterol levels reduces all-cause mortality and appears cost effective compared with accepted treatments in high-income countries Aims To assess the impact on healthcare re source utilization , costs , and quality of life over 15 years from 5 years of statin use in men without a history of myocardial infa rct ion in the West of Scotl and Coronary Prevention Study ( WOSCOPS ) . Methods Six thous and five hundred and ninety-five participants aged 45–54 years were r and omized to 5 years treatment with pravastatin ( 40 mg ) or placebo . Linkage to routinely collected health records extended follow-up for secondary healthcare re source utilization to 15 years . The following new results are reported : cause-specific first and recurrent cardiovascular hospital admissions including myocardial infa rct ion , heart failure , stroke , coronary revascularization and angiography ; non-cardiovascular hospitalization ; days in hospital ; quality -adjusted life years ( QALYs ) ; costs of pravastatin treatment , treatment safety monitoring , and hospital admissions . Results Output:	LIMITATIONS AND CONCLUSIONS The finding that few CEA models included mortality inputs from individual RCTs of lipid-lowering therapy may be surprising , as one might expect that treatment efficacy should be based on robust clinical evidence .
MS22535	*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 Carcinoma of the esophagus traditionally has been treated by surgery or radiation therapy ( RT ) , but 5-year overall survival rates have been only 5 % to 10 % . We previously reported results of a study conducted from January 1986 to April 1990 of combined chemotherapy and RT vs RT alone when an interim analysis revealed significant benefit for combined therapy . OBJECTIVE To report the long-term outcomes of a previously reported trial design ed to determine if adding chemotherapy during RT improves the survival rate of patients with esophageal carcinoma . DESIGN R and omized controlled trial conducted 1985 to 1990 with follow-up of at least 5 years , followed by a prospect i ve cohort study conducted between May 1990 and April 1991 . SETTING Multi-institution participation , ranging from tertiary academic referral centers to general community practice s. PATIENTS Patients had squamous cell or adenocarcinoma of the esophagus , T1 - 3 N0 - 1 M0 , adequate renal and bone marrow reserve , and a Karnofsky score of at least 50 . Interventions Combined modality therapy ( n = 134 ) : 50 Gy in 25 fractions over 5 weeks , plus cisplatin intravenously on the first day of weeks 1 , 5 , 8 , and 11 , and fluorouracil , 1 g/m2 per day by continuous infusion on the first 4 days of weeks 1 , 5 , 8 , and 11 . In the r and omized study , combined therapy was compared with RT only ( n = 62 ) : 64 Gy in 32 fractions over 6.4 weeks . MAIN OUTCOME MEASURES Overall survival , patterns of failure , and toxic effects . RESULTS Combined therapy significantly increased overall survival compared with RT alone . In the r and omized part of the trial , at 5 years of follow-up the overall survival for combined therapy was 26 % ( 95 % confidence interval [ CI ] , 15%-37 % ) compared with 0 % following RT . In the succeeding nonr and omized part , combined therapy produced a 5-year overall survival of 14 % ( 95 % CI , 6%-23 % ) . Persistence of disease ( despite therapy ) was the most common mode of treatment failure ; however , it was less common in the groups receiving combined therapy ( 34/130 [ 26 % ] ) than in the group treated with RT only ( 23/62 [ 37 % ] ) . Severe acute toxic effects also were greater in the combined therapy groups . There were no significant differences in severe late toxic effects between the groups . However , chemotherapy could be administered as planned in only 89 ( 68 % ) of 130 patients ( 10 % had life-threatening toxic effects with combined therapy vs 2 % in the RT only group ) . CONCLUSION Combined therapy increases the survival of patients who have squamous cell or adenocarcinoma of the esophagus , T1 - 3 N0 - 1 M0 , compared with RT alone PURPOSE To compare the local/regional control , survival , and toxicity of combined-modality therapy using high-dose ( 64.8 Gy ) versus st and ard-dose ( 50.4 Gy ) radiation therapy for the treatment of patients with esophageal cancer . PATIENTS AND METHODS A total of 236 patients with clinical stage T1 to T4 , N0/1 , M0 squamous cell carcinoma or adenocarcinoma selected for a nonsurgical approach , after stratification by weight loss , primary tumor size , and histology , were r and omized to receive combined-modality therapy consisting of four monthly cycles of fluorouracil ( 5-FU ) ( 1,000 mg/m(2)/24 hours for 4 days ) and cisplatin ( 75 mg/m(2 ) bolus day 1 ) with concurrent 64.8 Gy versus the same chemotherapy schedule but with concurrent 50.4 Gy . The trial was stopped after an interim analysis . The median follow-up was 16.4 months for all patients and 29.5 months for patients still alive . RESULTS For the 218 eligible patients , there was no significant difference in median survival ( 13.0 v 18.1 months ) , 2-year survival ( 31 % v 40 % ) , or local/regional failure and local/regional persistence of disease ( 56 % v 52 % ) between the high-dose and st and ard-dose arms . Although 11 treatment-related deaths occurred in the high-dose arm compared with two in the st and ard-dose arm , seven of the 11 deaths occurred in patients who had received 50.4 Gy or less . CONCLUSION The higher radiation dose did not increase survival or local/regional control . Although there was a higher treatment-related mortality rate in the patients assigned to the high-dose radiation arm , it did not seem to be related to the higher radiation dose . The st and ard radiation dose for patients treated with concurrent 5-FU and cisplatin chemotherapy is 50.4 Gy Background This retrospective study on early and locally advanced esophageal cancer was conducted to evaluate locoregional failure and its impact on survival by comparing involved field radiotherapy ( IFRT ) with elective nodal irradiation ( ENI ) in combination with concurrent chemotherapy . Methods We assessed all patients with esophageal cancer of stages I-IV treated with definitive radiotherapy from June 2000 to March 2014 . Between 2000 and 2011 , ENI was used for all cases excluding high age cases . After Feb 2011 , a prospect i ve study about IFRT was started , and therefore IFRT was used since then for all cases . Concurrent chemotherapy regimen was nedaplatin ( 80 mg/m2 at D1 and D29 ) and 5-fluorouracil ( 800 mg/m2 at D1 - 4 and D29 - 32 ) . Results Of the 239 consecutive patients assessed ( 120 ENI vs. 119 IFRT ) , 59 patients ( 24.7 % ) had stage IV disease and all patients received at least one cycle of chemotherapy . The median follow-up time for survivors was 34.0 months . There were differences in 3-year local control ( 44.8 % vs. 55.5 % , p = 0.039 ) , distant control ( 53.8 % vs. 69.9 % , p = 0.021 ) and overall survival ( 34.8 % vs. 51.6 % , p = 0.087 ) rates between ENI vs. IFRT , respectively . Patients treated with IFRT ( 8 % ) demonstrated a significantly lower risk ( p = 0.047 ) of high grade late toxicities than with ENI ( 16 % ) . IFRT did not increase the risk of initially uninvolved or isolated nodal failures ( 27.5 % in ENI and 13.4 % in IFRT ) . Conclusions Nodal failure rates in clinical ly uninvolved nodal stations were not increased with IFRT when compared to ENI . IFRT also result ed in significantly decreased esophageal toxicity , suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients . Both tendencies of improved loco-regional progression-free survival and a significant increased overall survival rate favored the IFRT arm over the ENI arm in this study Background : The aim of this study was to investigate the feasibility of involved-field irradiation ( IFI ) for the treatment of cervical and upper-thoracic esophageal cancer with concurrent chemoradiation . Patients and Methods : 102 eligible patients with cervical or upper-thoracic esophageal cancer were treated with concurrent chemoradiation and r and omized to either an IFI or elective nodal irradiation ( ENI ) group . Results : Adverse events included infection ( 27.4 vs. 64.7 % ) and nausea ( 25.4 vs. 54.9 % ) , with a statistically significant difference between the IFI and the ENI group ( p = 0.008 and 0.028 , respectively ) . No difference was seen for late radiation reaction . The cumulative incidence of local/regional failure ( 13.7 vs. 17.6 % ) and regional lymph failure ( 7.8 vs. 9.8 % ) showed no statistically significant difference between the IFI versus the ENI group ( p = 0.837 and 0.837 , respectively ) . A nodal out-field relapse rate of only 2 % was seen in the IFI group . 3-year survival rates for the ENI and IFI group were 41.3 and 32.0 % , respectively ( p = 0.58 ) , and 3-year local control rates were 85.7 and 80.1 % , respectively ( p = 0.34 ) . Conclusion : IFI was acceptable for cervical and upper-thoracic esophageal cancer with a decrease in acute toxicities and no increase in lymph node failure PURPOSE To evaluate the local control , survival , and toxicity associated with three-dimensional conformal radiotherapy ( 3D-CRT ) for squamous cell carcinoma ( SCC ) of the esophagus , to determine the appropriate target volumes , and to determine whether elective nodal irradiation is necessary in these patients . METHODS AND MATERIAL S A prospect i ve study of 3D-CRT was undertaken in patients with esophageal SCC without distant metastases . Patients received 68.4 Gy in 41 fractions over 44 days using late-course accelerated hyperfractionated 3D-CRT . Only the primary tumor and positive lymph nodes were irradiated . Isolated out-of-field regional nodal recurrence was defined as a recurrence in an initially uninvolved regional lymph node . RESULTS All 53 patients who made up the study population tolerated the irradiation well . No acute or late Grade 4 or 5 toxicity was observed . The median survival time was 30 months ( 95 % confidence interval , 17.7 - 41.8 ) . The overall survival rate at 1 , 2 , and 3 years was 77 % , 56 % , and 41 % , respectively . The local control rate at 1 , 2 , and 3 years was 83 % , 74 % , and 62 % , respectively . Thirty-nine of the 53 patients ( 74 % ) showed treatment failure . Seventeen of the 39 ( 44 % ) developed an in-field recurrence , 18 ( 46 % ) distant metastasis with or without regional failure , and 3 ( 8 % ) an isolated out-of-field nodal recurrence only . One patient died of disease in an unknown location . CONCLUSIONS In patients treated with 3D-CRT for esophageal SCC , the omission of elective nodal irradiation was not associated with a significant amount of failure in lymph node regions not included in the planning target volume . Local failure and distant metastases remained the predominant problems Background and purpose The purpose of this study was to evaluate the radiotherapy ( RT ) quality assurance ( QA ) for JCOG 0303 . Methods and material sJCOG 0303 was a multi-center phase II/III trial that compared two types of chemotherapy administered concomitantly with RT for locally advanced esophageal cancer . RT requirements included a total dose of 60 Gy in 30 fractions and CTV with a 2-cm margin cranio-caudally to the primary tumor . The QA assessment was given as per protocol ( PP ) , deviation acceptable ( DA ) , violation unacceptable ( VU ) , and incomplete/not evaluable following predefined criteria for quality parameters . Results A total of 142 cases were accrued . After excluding 36 incomplete/not evaluable , 106 ( 75 % ) were fully evaluable for RT quality review . Of these 106 , there were 4 VU ( 4 % ) and overall RT compliance ( PP + DA ) was 96 % . Comparing the incidence of VU based on the numbers enrolled by institution , the highest quarter of enrollment ( ≥7 cases ) had no VU , while all VU ( 4 ; 11 % ) were from institutions enrolling < 7 patients . Conclusions The results of the RTQA assessment for JCOG 0303 were sufficient to provide reliable results . Additional improvements will be needed for institutions with low accrual rates Output:	Meanwhile , the incidences of esophageal and lung toxicities were significantly decreased in the IFI arm . These results suggest that IFI is a feasible treatment option for locally advanced esophageal cancer , especially to minimize irradiation-related toxicity
MS22536	*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: Risk-adjusted treatment stratification in T-cell acute lymphoblastic leukemias ( T-ALLs ) is currently based only on early response to chemotherapy . We investigated the prognostic implication of hyperactivation of NOTCH pathway result ing from mutations of NOTCH1 or FBXW7 in children with T-ALL enrolled in EORTC-CLG trials . Overall , 80 out of 134 ( 60 % ) patients were NOTCH+ ( NOTCH1 and /or FBXW7 mutated ) . Although clinical presentations were not significantly associated with NOTCH status , NOTCH+ patients showed a better early response to chemotherapy as compared with NOTCH− patients , according to the rate of poor pre-phase ‘ responders ’ ( 25 % versus 44 % ; P=0.02 ) and the incidence of high minimal residual disease ( MRD ) levels ( 11 % ( 7/62 ) versus 32 % ( 10/31 ) ; P=0.01 ) at completion of induction . However , the outcome of NOTCH+ patients was similar to that of NOTCH− patients , with a 5-year event-free survival ( EFS ) of 73 % and 70 % ( P=0.82 ) , and 5-year overall survival of 82 % and 79 % ( P=0.62 ) , respectively . In patients with high MRD levels , the 5-year EFS rate was 0 % ( NOTCH+ ) versus 42 % ( NOTCH− ) , whereas in those with low MRD levels , the outcome was similar : 76 % ( NOTCH+ ) versus 78 % ( NOTCH− ) . The incidence of isolated central nervous system ( CNS ) relapses was relatively high in NOTCH1 + patients ( 8.3 % ) , which could be related to a higher propensity of NOTCH+ leukemic blasts to target the CNS PURPOSE Pediatric T-cell lymphoblastic lymphomas ( T-LBL ) are commonly treated on T-cell acute lymphoblastic leukemia ( T-ALL ) -derived protocol s. Therapeutic stratification based on response to the prephase treatment and on minimal residual disease assessment is well established in T-ALL but is not easy to extrapolate to T-LBL . The identification of molecular prognostic markers at diagnosis in T-LBL could provide an alternative for early therapeutic stratification . Our study determines the frequency and prognostic value of NOTCH1/FBXW7 mutations ( N/F(mut ) ) , FLASH deletion at chromosome 6q , and TCR rearrangements in a prospect i ve cohort of pediatric T-LBL . PATIENTS AND METHODS Pathologic sample s were obtained at diagnosis for 54 patients treated according to the EuroLB02 protocol in France . N/F(mut ) were identified by direct sequencing and allelic dosage was used to detect FLASH and TCRγ deletions , which were interpreted in conjunction with TCRγ , TCRβ , and TCRδ rearrangements . RESULTS N/F(mut ) were found in 55 % of T-LBL patients , in whom they were associated with improved event-free survival ( P < .01 ) and overall survival ( P < .01 ) . FLASH monoallelic deletions were observed in 18 % of patients ; they were predominantly N/F wild-type ( six of nine ) and tended to be of inferior prognosis ( P = .09 ) . Absence of biallelic TCRγ deletion ( ABD ) was seen in 7 % , all of which were N/F(mut ) and identified a poor prognosis group ( P = .02 ) . On multivariate analysis of N/F(mut ) , TCRγ ABD , and FLASH deletion , only N/F(mut ) was an independent factor for good prognosis . CONCLUSION Mutational status of NOTCH1/FBXW7 represents a promising marker for early therapeutic stratification in pediatric T-LBL PURPOSE The Group for Research in Adult Acute Lymphoblastic Leukemia ( GRAALL ) recently reported a significantly better outcome in T-cell acute lymphoblastic leukemia ( T-ALL ) harboring NOTCH1 and /or FBXW7 ( N/F ) mutations compared with unmutated T-ALL . Despite this , one third of patients with N/F-mutated T-ALL experienced relapse . PATIENTS AND METHODS In a series of 212 adult T-ALLs included in the multicenter r and omized GRAALL-2003 and -2005 trials , we search ed for additional N/K-RAS mutations and PTEN defects ( mutations and gene deletion ) . RESULTS N/F mutations were identified in 143 ( 67 % ) of 212 patients , and lack of N/F mutation was confirmed to be associated with a poor prognosis . K-RAS , N-RAS , and PTEN mutations/deletions were identified in three ( 1.6 % ) of 191 , 17 ( 8.9 % ) of 191 , and 21 ( 12 % ) of 175 patients , respectively . The favorable prognostic significance of N/F mutations was restricted to patients without RAS/PTEN abnormalities . These observations led us to propose a new T-ALL oncogenetic classifier defining low-risk patients as those with N/F mutation but no RAS/PTEN mutation ( 97 of 189 patients ; 51 % ) and all other patients ( 49 % ; including 13 % with N/F and RAS/PTEN mutations ) as high-risk patients . In multivariable analysis , this oncogenetic classifier remained the only significant prognostic covariate ( event-free survival : hazard ratio [ HR ] , 3.2 ; 95 % CI , 1.9 to 5.15 ; P < .001 ; and overall survival : HR , 3.2 ; 95 % CI , 1.9 to 5.6 ; P < .001 ) . CONCLUSION These data demonstrate that the presence of N/F mutations in the absence of RAS or PTEN abnormalities predicts good outcome in almost 50 % of adult T-ALL . Conversely , the absence of N/F or presence of RAS/PTEN alterations identifies the remaining cohort of patients with poor prognosis Activating mutations of the transmembrane receptor NOTCH1 are common in precursor T-cell lymphoblastic leukemia ( T-ALL ) . We systematic ally analyzed the impact of activating NOTCH1 mutations on early treatment response and long-term outcome in 157 patients with T-ALL of the pediatric ALL-Berlin-Frankfurt-Munster ( BFM ) 2000 study . We confirm previous results that NOTCH1 mutations occur in more than 50 % of T-ALL in children . In 82 patients ( 82/157 ; 52.2 % ) , activating NOTCH1 mutations were identified either in the heterodimerization ( 55/82 ; 67.1 % ) , in the PEST ( 13/82 ; 15.9 % ) , or in both domains ( 14/82 ; 17.0 % ) . The presence of NOTCH1 mutations was significantly correlated with a good prednisone response and favorable minimal residual disease ( MRD ) kinetics , which was independent from sex , age , white blood cell count , and T-cell immunophenotype at the time of diagnosis . Furthermore , activating NOTCH1 mutations specified a large subgroup of patients with an excellent prognosis . These findings indicate that in the context of the ALL-BFM 2000 treatment strategy , NOTCH1 mutations predict a more rapid early treatment response and a favorable long-term outcome in children with T-ALL Adult T-cell acute lymphoblastic leukemia ( T-ALL ) is an aggressive hematologic tumor associated with poor outcome . In this study , we analyzed the prognostic relevance of genetic alterations , immunophenotypic markers , and microarray gene expression signatures in a panel of 53 adult T-ALL patients treated in the Eastern Cooperative Oncology Group E2993 clinical trial . An early immature gene expression signature , the absence of bi-allelic TCRG deletion , CD13 surface expression , heterozygous deletions of the short arm of chromosome 17 , and mutations in IDH1/IDH2 and DNMT3A genes are associated with poor prognosis in this series . In contrast , expression of CD8 or CD62L , homozygous deletion of CDKN2A/CDKN2B , NOTCH1 and /or FBXW7 mutations , and mutations or deletions in the BCL11B tumor suppressor gene were associated with improved overall survival . Importantly , the prognostic relevance of CD13 expression and homozygous CDKN2A/CDKN2B deletions was restricted to cortical and mature T-ALLs . Conversely , mutations in IDH1/IDH2 and DNMT3A were specifically associated with poor outcome in early immature adult T-ALLs . This trial was registered at www . clinical trials.gov as # NCT00002514 Output:	We conclude that the presence of NOTCH1/FBXW7 mutations is an independent prognostic factor for 5-year EFS and 5-year OS
MS22537	*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 purpose of this study was to determine the effects of beta-alanine supplementation and high-intensity interval training ( HIIT ) on electromyographic fatigue threshold ( EMGFT ) and efficiency of electrical activity ( EEA ) . A total of 46 men completed four , 2-min work bouts on a cycle ergometer . Using bipolar surface electrodes , the EMG amplitude was averaged and plotted over the 2-min . The result ing slopes were used to calculate EMGFT and EEA . Following initial testing , all participants were r and omly assigned to either placebo ( PL ; n = 18 ) , beta-alanine ( BA ; n = 18 ) or control groups ( CON ; n = 10 ) . Following r and omization , participants engaged in 6 weeks of HIIT training . Significant improvements in EMGFT and EEA result ed for both training groups . In conclusion , HIIT appeared to be the primary stimulus effecting EMGFT or EEA , suggesting adaptations from HIIT may be more influential than increasing skeletal muscle carnosine levels on delaying fatigue in recreationally active men Summary .The effect of beta-alanine ( β-Ala ) alone or in combination with creatine monohydrate ( Cr ) on aerobic exercise performance is unknown . The purpose of this study was to examine the effects of 4 weeks of β-Ala and Cr supplementation on indices of endurance performance . Fifty-five men ( 24.5 ± 5.3 yrs ) participated in a double-blind , placebo-controlled study and r and omly assigned to one of 4 groups ; placebo ( PL , n = 13 ) , creatine ( Cr , n = 12 ) , beta-alanine ( β-Ala , n = 14 ) , or beta-alanine plus creatine ( CrBA , n = 16 ) . Prior to and following supplementation , participants performed a grade d exercise test on a cycle ergometer to determine VO2peak , time to exhaustion ( TTE ) , and power output , VO2 , and percent VO2peak associated with VT and LT . No significant group effects were found . However , within groups , a significant time effect was observed for CrBa on 5 of the 8 parameters measured . These data suggest that CrBA may potentially enhance endurance performance The aim of this study was to examine the effect of β-alanine supplementation on repeated sprint performance during an intermittent exercise protocol design ed to replicate games play . Sixteen elite and twenty non-elite game players performed the Loughborough Intermittent Shuttle Test ( LIST ) on two separate occasions . Trials were separated by 4 weeks of supplementation with either β-alanine ( BA ) or maltodextrin ( MD ) . There was no deterioration in sprint times from Set 1 to Set 6 of the LIST in either group prior to supplementation ( elite : P = 0.92 ; non-elite : P = 0.12 ) . Neither BA nor MD supplementation affected sprint times . Blood lactate concentrations were elevated during exercise in both groups , with no effect of supplementation . β-Alanine supplementation did not significantly improve sprint performance during the LIST . Neither group showed a performance decrement prior to supplementation , which might have masked any benefit from increased muscle buffering capacity due to β-alanine supplementation Beta-alanine may benefit short- duration , high-intensity exercise performance . The aim of this r and omized double-blind placebo-controlled study was to examine the effects of beta-alanine supplementation on aspects of muscular performance in highly trained cyclists . Sixteen highly trained cyclists ( mean ± SD ; age = 24 ± 7 yr ; mass = 70 ± 7 kg ; VO2max = 67 ± 4 ml · kg(-1 ) · min(-1 ) ) supplemented with either beta-alanine ( n = 8 , 65 mg · kg - 1BM ) or a placebo ( n = 8 ; dextrose monohydrate ) over 4 weeks . Pre- and postsupplementation cyclists performed a 4-minute maximal cycling test to measure average power and 30 reciprocal maximal isokinetic knee contractions at a fixed angular velocity of 180 ° · sec(-1 ) to measure average power/repetition , total work done ( TWD ) , and fatigue index ( % ) . Blood pH , lactate ( La- ) and bicarbonate ( HCO3- ) concentrations were measured pre- and postisokinetic testing at baseline and following the supplementation period . Beta-alanine supplementation was 44 % likely to increase average power output during the 4-minute cycling time trial when compared with the placebo , although this was not statistically significant ( p = .25 ) . Isokinetic average power/repetition was significantly increased post beta-alanine supplementation compared with placebo ( beta-alanine : 6.8 ± 9.9 W , placebo : -4.3 ± 9.5 W , p = .04 , 85 % likely benefit ) , while fatigue index was significantly reduced ( p = .03 , 95 % likely benefit ) . TWD was 89 % likely to be improved following beta-alanine supplementation ; however , this was not statistically significant ( p = .09 ) . There were no significant differences in blood pH , lactate , and HCO3- between groups ( p > .05 ) . Four weeks of beta-alanine supplementation result ed in worthwhile changes in time-trial performance and short- duration muscular force production in highly trained cyclists Background Ageing is associated with a significant reduction in skeletal muscle carnosine which has been linked with a reduction in the buffering capacity of muscle and in theory , may increase the rate of fatigue during exercise . Supplementing beta-alanine has been shown to significantly increase skeletal muscle carnosine . The purpose of this study , therefore , was to examine the effects of ninety days of beta-alanine supplementation on the physical working capacity at the fatigue threshold ( PWCFT ) in elderly men and women . Methods Using a double-blind placebo controlled design , twenty-six men ( n = 9 ) and women ( n = 17 ) ( age ± SD = 72.8 ± 11.1 yrs ) were r and omly assigned to either beta-alanine ( BA : 800 mg × 3 per day ; n = 12 ; CarnoSyn ™ ) or Placebo ( PL ; n = 14 ) group . Before ( pre ) and after ( post ) the supplementation period , participants performed a discontinuous cycle ergometry test to determine the PWCFT . Results Significant increases in PWCFT ( 28.6 % ) from pre- to post-supplementation were found for the BA treatment group ( p < 0.05 ) , but no change was observed with PL treatment . These findings suggest that ninety days of BA supplementation may increase physical working capacity by delaying the onset of neuromuscular fatigue in elderly men and women . Conclusion We suggest that BA supplementation , by improving intracellular pH control , improves muscle endurance in the elderly . This , we believe , could have importance in the prevention of falls , and the maintenance of health and independent living in elderly men and women Abstract Smith-Ryan , AE , Fukuda , DH , Stout , JR , and Kendall , KL . High-velocity intermittent running : effects of beta-alanine supplementation . J Strength Cond Res 26(10 ) : 2798–2805 , 2012—The use of & bgr;-alanine in sport is widespread . However , the effects across all sport activities are inconclusive . The purpose of this study was to evaluate the effects of & bgr;-alanine supplementation on high-intensity running performance and critical velocity ( CV ) and anaerobic running capacity ( ARC ) . Fifty recreationally trained men were r and omly assigned , in a double-blind fashion , to a & bgr;-alanine group ( BA , 2 × 800 mg tablets , 3 times daily ; CarnoSyn ; n = 26 ) or placebo group ( PL , 2 × 800 mg maltodextrin tablets , 3 times daily ; n = 24 ) . A grade d exercise test ( GXT ) was performed to establish peak velocity ( PV ) . Three high-speed runs to exhaustion were performed at 110 , 100 , and 90 % of PV , with 15 minutes of rest between bouts . The distances achieved were plotted over the time to exhaustion ( TTE ) . Linear regression was used to determine the slope ( CV ) and y-intercept ( ARC ) of these relationships to assess aerobic and anaerobic performances , respectively . There were no significant treatment effects ( p > 0.05 ) on CV or ARC for either men or women . Additionally , no TTE effects were evident for bouts at 90–110%PV lasting 1.95–5.06 minutes . There seems to be no ergogenic effect of & bgr;-alanine supplementation on CV , ARC , or high-intensity running lasting approximately 2–5 minutes in either men or women in the current study Carnosine ( β-alanyl-l-histidine ) is found in high concentrations in skeletal muscle and chronic β-alanine ( BA ) supplementation can increase carnosine content . This placebo-controlled , double-blind study compared two different 8-week BA dosing regimens on the time course of muscle carnosine loading and 8-week washout , leading to a BA dose – response study with serial muscle carnosine assessment s throughout . Thirty-one young males were r and omized into three BA dosing groups : ( 1 ) high – low : 3.2 g BA/day for 4 weeks , followed by 1.6 g BA/day for 4 weeks ; ( 2 ) low – low : 1.6 g BA/day for 8 weeks ; and ( 3 ) placebo . Muscle carnosine in tibialis-anterior ( TA ) and gastrocnemius ( GA ) muscles was measured by 1H-MRS at weeks 0 , 2 , 4 , 8 , 12 and 16 . Flushing symptoms and blood clinical chemistry were trivial in all three groups and there were no muscle carnosine changes in the placebo group . During the first 4 weeks , the increase for high – low ( TA 2.04 mmol/kgww , GA 1.75 mmol/kgww ) was ~twofold greater than low – low ( TA 1.12 mmol/kgww , GA 0.80 mmol/kgww ) . 1.6 g BA/day significantly increased muscle carnosine within 2 weeks and induced continual rises in already augmented muscle carnosine stores ( week 4–8 , high – low regime ) . The dose – response showed a carnosine increase of 2.01 mmol/kgww per 100 g of consumed BA , which was only dependent upon the total accumulated BA consumed ( within a daily intake range of 1.6–3.2 g BA/day ) . Washout rates were gradual ( 0.18 mmol/kgww and 0.43 mmol/kgww/week ; ~2%/week ) . In summary , the absolute increase in muscle carnosine is only dependent upon the total BA consumed and is not dependent upon baseline muscle carnosine , the muscle type , or the daily amount of supplemented BA Background β-Alanine ( βA ) has been shown to improve performance during cycling . This study was the first to examine the effects of βA supplementation on the onset of blood lactate accumulation ( OBLA ) during incremental treadmill running . Methods Seventeen recreationally-active men ( mean ± SE 24.9 ± 4.7 yrs , 180.6 ± 8.9 cm , 79.25 ± 9.0 kg ) participated in this r and omized , double-blind , placebo-controlled pre/post test 2-treatment experimental design . Subjects participated in two incremental treadmill tests before and after 28 days of supplementation with either βA ( 6.0 g·d-1)(βA , n = 8) or an equivalent dose of Maltodextrin as the Placebo ( PL , n = 9 ) . Heart rate , percent heart rate maximum ( % HRmax ) , % VO2max@OBLA ( 4.0 mmol . L-1 blood lactate concentration ) and VO2max ( L.min-1 ) were determined for each treadmill test . Friedman test was used to determine within group differences ; and Mann-Whitney was used to determine between group differences for pre and post values ( p < 0.05 ) . Results The βA group experienced a significant rightward shift in HR@OBLA beats.min-1 ( p < 0.01 ) pre/post ( 161.6 ± 19.2 to 173.6 ± 9.9 ) but remained unchanged in the PL group ( 166.8 ± 15.8 to 169.6 ± 16.1 ) . The % HRmax@OBLA increased ( p < 0.05 ) pre/post in the βA group ( 83.0 % ± 9.7 to 88.6 % ± 3.7 ) versus no change in the PL group ( 86.3 ± % 4.8 to 87.9 % ± 7.2 ) . The % VO2max@OBLA increased ( p < 0.05 ) in the βA group pre/post ( 69.1 ± 11.0 to 75.6 ± 10.7 ) but remained unchanged in the PL group ( 73.3 ± 7.3 to 74.3 ± 7.3 ) . VO2max ( L.min-1 ) decreased ( p < 0.01 ) in the βA group pre Output:	Summary / conclusions & bgr;-alanine had a significant overall effect while subgroup analyses revealed a number of modifying factors . These data allow individuals to make informed decisions as to the likelihood of an ergogenic effect with & bgr;-alanine supplementation based on their chosen exercise modality
MS22538	*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 — Clinical observational studies on heart failure ( HF ) deal mostly with hospitalized patients , few with chronic out patients , all with no or limited longitudinal observation . Methods and Results —This is a multicenter , nationwide , prospect i ve observational trial on a population of 5610 patients , 1855 hospitalized for acute HF ( AHF ) and 3755 out patients with chronic HF ( CHF ) , followed up for 1 year . The cumulative total mortality rate at 1 year was 24 % in AHF ( 19.2 % in 797 patients with de novo HF and 27.7 % in 1058 with worsening HF ) and 5.9 % in CHF . Cardiovascular deaths accounted for 73.1 % and 65.3 % and HF deaths for 42.4 % and 40.5 % of total deaths in AHF and CHF patients , respectively . One-year hospitalization rates were 30.7 % in AHF and 22.7 % in CHF patients . Among the independent predictors of 1-year all-cause death , age , low systolic blood pressure , anemia , and renal dysfunction were identified in both acute and chronic patients . A few additional variables were significant only in AHF ( signs of cerebral hypoperfusion , low serum sodium , chronic obstructive pulmonary disease , and acute pulmonary edema ) , whereas others were observed only in CHF patients ( lower body mass index , higher heart rate , New York Heart Association class , large QRS , and severe mitral regurgitation ) . Conclusions —In this contemporary data set , patients with CHF had a relatively low mortality rate compared with those with AHF . Rates of adverse outcomes in patients admitted for AHF remain very high either in-hospital or after discharge . Most deaths were cardiovascular in origin and ≈40 % of deaths were directly related to HF AIMS We identified easily obtained baseline characteristics associated with outcomes in patients with chronic heart failure ( HF ) and elevated heart rate ( HR ) receiving contemporary guideline -recommended therapy in the SHIFT trial , and used them to develop a prognostic model . METHODS We selected the 10 best predictors for each of four outcomes ( cardiovascular death or HF hospitalisation ; all-cause mortality ; cardiovascular mortality ; and HF hospitalisation ) . All variables with p<0.05 for association were entered into a forward stepwise Cox regression model . Our initial analysis excluded baseline therapies , though r and omisation to ivabradine or placebo was forced into the model for the composite endpoint and HF hospitalisation . RESULTS Increased resting HR , low ejection fraction , raised creatinine , New York Heart Association class III/IV , longer duration of HF , history of left bundle branch block , low systolic blood pressure and , for three models , age were strong predictors of all outcomes . Additional predictors were low body mass index , male gender , ischaemic HF , low total cholesterol , no history of hyperlipidaemia or dyslipidaemia and presence of atrial fibrillation/flutter . The c-statistics for the four outcomes ranged from 67.6 % to 69.5 % . There was no evidence for lack of fit of the models with the exception of all-cause mortality ( p=0.017 ) . Similar results were found including baseline therapies . CONCLUSION The SHIFT Risk Model includes simple , readily obtainable clinical characteristics to produce important prognostic information in patients with chronic HF , systolic dysfunction , and elevated HR . This may help better calibrate management to individual patient risk Objectives The goal of this study was to determine the relative contribution of major lifestyle factors on the development of heart failure ( HF ) in older adults . Background HF incurs high morbidity , mortality , and health care costs among adults ≥65 years of age , which is the most rapidly growing segment of the U.S. population . Methods We prospect ively investigated separate and combined associations of lifestyle risk factors with incident HF ( 1,380 cases ) over 21.5 years among 4,490 men and women in the Cardiovascular Health Study , which is a community-based cohort of older adults . Lifestyle factors included 4 dietary patterns ( Alternative Healthy Eating Index , Dietary Approaches to Stop Hypertension , an American Heart Association 2020 dietary goals score , and a Biologic pattern , which was constructed using previous knowledge of cardiovascular disease dietary risk factors ) , 4 physical activity metrics ( exercise intensity , walking pace , energy expended in leisure activity , and walking distance ) , alcohol intake , smoking , and obesity . Results No dietary pattern was associated with developing HF ( p > 0.05 ) . Walking pace and leisure activity were associated with a 26 % and 22 % lower risk of HF , respectively ( pace > 3 mph vs. < 2 mph ; hazard ratio [ HR ] : 0.74 ; 95 % confidence interval [ CI ] : 0.63 to 0.86 ; leisure activity ≥845 kcal/week vs. < 845 kcal/week ; HR : 0.78 ; 95 % CI : 0.69 to 0.87 ) . Modest alcohol intake , maintaining a body mass index < 30 kg/m2 , and not smoking were also independently associated with a lower risk of HF . Participants with ≥4 healthy lifestyle factors had a 45 % ( HR : 0.55 ; 95 % CI : 0.42 to 0.74 ) lower risk of HF . Heterogeneity by age , sex , cardiovascular disease , hypertension medication use , and diabetes was not observed . Conclusions Among older U.S. adults , physical activity , modest alcohol intake , avoiding obesity , and not smoking , but not dietary patterns , were associated with a lower risk of HF Background —Heart failure ( HF ) is a prevalent and deadly disease , and preventive strategies focused on at-risk individuals are needed . Current HF prediction models have not examined HF subtypes . We sought to develop and vali date risk prediction models for HF with preserved and reduced ejection fraction ( HFpEF , HFrEF ) . Methods and Results —Of 28,820 participants from 4 community-based cohorts , 982 developed incident HFpEF and 909 HFrEF during a median follow-up of 12 years . Three cohorts were combined , and a 2:1 r and om split was used for derivation and internal validation , with the fourth cohort as external validation . Models accounted for multiple competing risks ( death , other HF subtype , and unclassified HF ) . The HFpEF-specific model included age , sex , systolic blood pressure , body mass index , antihypertensive treatment , and previous myocardial infa rct ion ; it had good discrimination in derivation ( c-statistic 0.80 ; 95 % confidence interval [ CI ] , 0.78–0.82 ) and validation sample s ( internal : 0.79 ; 95 % CI , 0.77–0.82 and external : 0.76 ; 95 % CI : 0.71–0.80 ) . The HFrEF-specific model additionally included smoking , left ventricular hypertrophy , left bundle branch block , and diabetes mellitus ; it had good discrimination in derivation ( c-statistic 0.82 ; 95 % CI , 0.80–0.84 ) and validation sample s ( internal : 0.80 ; 95 % CI , 0.78–0.83 and external : 0.76 ; 95 % CI , 0.71–0.80 ) . Age was more strongly associated with HFpEF , and male sex , left ventricular hypertrophy , bundle branch block , previous myocardial infa rct ion , and smoking with HFrEF ( P value for each comparison ⩽0.02 ) . Conclusions —We describe and vali date risk prediction models for HF subtypes and show good discrimination in a large sample . Some risk factors differed between HFpEF and HFrEF , supporting the notion of pathogenetic differences among HF subtypes BACKGROUND AND AIMS Hospitalized patients with heart failure who are malnourished present a worse prognosis than those with an adequate nutritional status . We undertook this study to assess whether a nutritional intervention in malnourished hospitalized patients with heart failure benefits morbidity and mortality . METHODS A multicenter , r and omized , controlled clinical trial was conducted . A total of 120 malnourished hospitalized patients due to acute heart failure were r and omised to conventional heart failure treatment or conventional heart failure treatment combined with an individualized nutritional intervention . The primary endpoint of this study was a composite of all-cause death or readmission for worsening of HF , with a maximum follow-up of 12 months . Analysis was by intention to treat . RESULTS Recruitment was stopped early according to the study protocol after completing the follow-up of the first 120 patients enrolled ( 59 in the intervention group and 61 in the control group ) . Both groups were homogeneous in baseline characteristics . At 12 months , the primary outcome occurred in 27.1 % of patients in the intervention group and in 60.7 % of patients in the control group ( hazard ratio 0.45 ; 95 % confidence interval [ CI ] , 0.19 - 0.62 , p = 0.0004 ) . In total , 20.3 % of patients died in the intervention group and 47.5 % in the control group ( hazard ratio 0.37 , 95 % CI , 0.19 - 0.72 , p = 0.003 ) . Readmission due to heart failure was also lower in the intervention group ( 10.2 vs. 36.1 % , p = 0.001 ) . CONCLUSION Nutritional intervention in malnourished hospitalized patients with heart failure reduces the risk of death from any cause and the risk of readmission for worsening of heart failure ( Clinical Trial.govNCT01472237 ) Aims We have investigated the role of muscle mass , natriuretic peptides and adipokines in explaining the obesity paradox . Background The obesity paradox relates to the association between obesity and increased survival in patients with coronary heart disease ( CHD ) or heart failure ( HF ) . Methods Prospect i ve study of 4046 men aged 60–79 years followed up for a mean period of 11 years , during which 1340 deaths occurred . The men were divided according to the presence of doctor diagnosed CHD and HF : ( i ) no CHD or HF ii ) , with CHD ( no HF ) and ( iii ) with HF . Results Overweight ( BMI 25–9.9 kg/m2 ) and obesity ( BMI ≥ 30 kg/m2 ) were associated with lower mortality risk compared to men with normal weight ( BMI 18.5–24.9 kg/m2 ) in those with CHD [ hazards ratio ( HR ) 0.71 ( 0.56,0.91 ) and 0.77 ( 0.57,1.04 ) ; p = 0.04 for trend ] and in those with HF [ HR 0.57 ( 0.28,1.16 ) and 0.41 ( 0.16,1.09 ; p = 0.04 for trend ) . Adjustment for muscle mass and NT-proBNP attenuated the inverse association in those with CHD ( no HF ) [ HR 0.78 ( 0.61,1.01 ) and 0.96 ( 0.68,1.36 ) p = 0.60 for trend ) but made minor differences to those with HF [ p = 0.05 ] . Leptin related positively to mortality in men without HF but inversely to mortality in those with HF ; adjustment for leptin abolished the BMI mortality association in men with HF [ HR 0.82 ( 0.31,2.20 ) and 0.99 ( 0.27,3.71 ) ; p = 0.98 for trend ] . Conclusion The lower mortality risk associated with excess weight in men with CHD without HF may be due to higher muscle mass . In men with HF , leptin ( possibly reflecting cachexia ) explain the inverse association Background —Skeletal muscle dysfunction and exercise intolerance are clinical hallmarks of patients with heart failure . These have been linked to a progressive catabolic state , skeletal muscle inflammation , and impaired oxidative metabolism . Previous studies suggest beneficial effects of & ohgr;-3 polyunsaturated fatty acids and glutamine on exercise performance and muscle protein balance . Methods and Results —In a r and omized double-blind , placebo-controlled trial , 31 patients with heart failure were r and omized to either L-alanyl-L-glutamine ( 8 g/d ) and polyunsaturated fatty acid ( 6.5 g/d ) or placebo ( safflower oil and milk powder ) for 3 months . Cardiopulmonary exercise testing , dual-energy x-ray absorptiometry , 6-minute walk test , h and grip strength , functional muscle testing , echocardiography , and quality of life and lateral quadriceps muscle biopsy were performed at baseline and at follow-up . Oxidative capacity and metabolic gene expression were analyzed on muscle biopsies . No differences in muscle function , echocardiography , 6-minute walk test , or h and grip strength and a nonsignificant increase in peak VO2 in the treatment group Output:	Nutritional disorders are prevalent in patients with CHF and play a significant role in the incidence , course , and prognosis of the disease .
MS22539	*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 For patients who undergo gastrectomy for gastric cancer , systematic follow-up evaluation to detect recurrent lesions is recommended , although the benefits of a surveillance program using short-term imaging studies have not been evaluated . Methods This study review ed the clinical data of patients who underwent curative surgery for gastric cancer using a prospect i ve data base . Patients with recurrence were classified according to surveillance interval as follows : ≤3 , 3–6 , and 6–12 months . Results Of the 2785 patients who underwent curative surgery for gastric cancer , 376 ( 13.5 % ) had intraabdominal recurrences , excluding the stomach . Multivariable analysis showed that a short surveillance interval did not increase the post-recurrence survival duration ( with 6–12 months as the reference : ≤3 months : hazard ratio [ HR ] 0.954 ; 95 % confidence interval [ CI ] 0.689–1.323 ; 3–6 months : HR 0.994 , 95 % CI 0.743–1.330 ) . In addition , short surveillance intervals did not increase overall survival ( with 6–12 months as the reference : ≤3 months : HR 0.969 ; 95 % CI 0.699–1.342 ; 3–6 months : HR 0.955 ; 95 % CI 0.711–1.285 ) . In contrast to the surveillance interval , age , cancer stage , symptoms at recurrence , and recurrence time after gastrectomy were factors associated with both post-recurrence survival and overall survival . Conclusions Although the detection of recurrence before symptoms helped to prolong both post-recurrence survival and overall survival , shortening the surveillance interval to less than 6 months did not improve either the patient ’s post-recurrence survival or overall survival . Hence , it is not recommended that asymptomatic patients undergo surveillance involving imaging studies more often than once a year Purpose In a retrospective analysis , adjuvant intensity-modulated radiation therapy ( IMRT ) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy ( 3D-CRT ) and conventional chemotherapy . We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy , or 3D-CRT and conventional chemotherapy . Patients and methods Between 2001 and 2008 , 65 consecutive gastric cancer patients received either 3D-CRT ( n = 27 ) or IMRT ( n = 38 ) following tumor resection . Chemotherapy comprised predominantly 5-fluorouracil/folinic acid ( 5-FU/FA ) in the earlier cohort and capecitabine plus oxaliplatin ( XELOX ) in the latter . The primary endpoints were overall survival ( OS ) and disease-free survival ( DFS ) . Results Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups , respectively ( p = 0.0602 ) . Actuarial 5-year OS rates were 26 and 47 % , respectively . Within the IMRT group , XELOX gave better results than 5-FU/FA in terms of OS , but this difference was not statistically significant . The primary cause of death in both groups was distant metastasis . Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups , respectively ( p = 0.0693 ) . Actuarial 5-year DFS rates were 22 and 44 % , respectively . Among patients receiving 5-FU/FA , DFS tended to be better in the IMRT group , but this was not statistically significant . A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients . No late toxicity exceeding grade 3 or secondary tumors were observed . Conclusion After a median follow-up period of over 5 years , OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group . Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity . ZusammenfassungZielsetzungIn einer retrospektiven Analyse verbesserte die adjuvante Radiochemotherapie mit intensitätsmodulierter Strahlentherapie ( IMRT ) und moderner Chemotherapie das Überleben von Patienten mit lokal fortgeschrittenem Magenkarzinom gegenüber der Kombination aus 3-dimensionaler konformaler Strahlentherapie ( 3D-CRT ) und konventioneller Chemotherapie . Wir berichten nun über die Langzeitergebnisse von zwei aufein and er folgenden Patientenkohorten , die entweder mit IMRT in Kombination mit einer intensivierten Chemotherapie [ Capecitabin/Oxaliplatin ( XELOX ) , spätere Kohorte ] oder mit 3D-CRT und konventioneller Chemotherapie [ 5-Fluorouracil/Folinsäure ( 5-FU/FA ) , frühere Kohorte ] beh and elt worden waren . Patienten und Method enIn den Jahren 2001–2008 wurden 65 Patienten konsekutiv wegen eines Magenkarzinoms entweder mit 3D-CRT ( n = 27 ) oder IMRT ( n = 38 ) beh and elt . Die Chemotherapie beinhaltete überwiegend 5-FU/FA in der früheren Kohorte und XELOX in der späteren Kohorte . Primäre Endpunkte waren das Gesamtüberleben ( OS ) und krankheitsfreie Überleben (DFS).ErgebnisseDas mediane OS betrug in der 3D-CRT-Gruppe 18 Monate und in der IMRT-Gruppe 43 Monate ( p = 0,0602 ) . Das aktuarische 5-Jahres-OS lag nach 3D-CRT bei 26 % und nach IMRT bei 47 % . Innerhalb der IMRT-Gruppe war die intensivierte Chemotherapie der konventionellen hinsichtlich des OS überlegen , der Unterschied erreichte aber keine statistische Signifikanz . Zum Tode führten in beiden Gruppen vorwiegend Fernmetastasen außerhalb des Bestrahlungsfelds . Das mediane DFS betrug 14 Monate in der 3D-CRT-Gruppe und 35 Monate in der IMRT-Gruppe ( p = 0,0693 ) . Das aktuarische 5-Jahres-DFS lag bei 22 % in der 3D-CRT und 44 % in der IMRT-Gruppe . Innerhalb der Patientengruppe , die lediglich 5-FU/FA erhalten hatte , zeigte sich ein statistisch nicht signifikanter Vorteil für die IMRT . Eine entsprechende Analyse in der XELOX-Gruppe war nicht möglich , da die Radiotherapie nahezu nie als 3D-CRT durchgeführt worden war . Eine Spättoxizität > Grad 3 und Sekundärtumoren wurden nicht beobachtet . SchlussfolgerungNach einer medianen Beobachtungsdauer von > 5 Jahren war sowohl das OS als auch das DFS in der Patientengruppe mit IMRT/XELOX-Beh and lung deutlich verbessert . Die Langzeitbeobachtung erbrachte keine klinischen Hinweise auf Nephrotoxizität oder therapiebedingte Sekundärtumoren PURPOSE Surgical resection of gastric cancer has produced suboptimal survival despite multiple r and omized trials that used postoperative chemotherapy or more aggressive surgical procedures . We performed a r and omized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure ( LRF ) following surgery . We originally reported results with 4-year median follow-up . This up date , with a more than 10-year median follow-up , presents data on failure patterns and second malignancies and explores selected subset analyses . PATIENTS AND METHODS In all , 559 patients with primaries ≥ T3 and /or node-positive gastric cancer were r and omly assigned to observation versus radiochemotherapy after R0 resection . Fluorouracil and leucovorin were administered before , during , and after radiotherapy . Radiotherapy was given to all LRF sites to a dose of 45 Gy . RESULTS Overall survival ( OS ) and relapse-free survival ( RFS ) data demonstrate continued strong benefit from postoperative radiochemotherapy . The hazard ratio ( HR ) for OS is 1.32 ( 95 % CI , 1.10 to 1.60 ; P = .0046 ) . The HR for RFS is 1.51 ( 95 % CI , 1.25 to 1.83 ; P < .001 ) . Adjuvant radiochemotherapy produced substantial reduction in both overall relapse and locoregional relapse . Second malignancies were observed in 21 patients with radiotherapy versus eight with observation ( P = .21 ) . Subset analyses show robust treatment benefit in most subsets , with the exception of patients with diffuse histology who exhibited minimal nonsignificant treatment effect . CONCLUSION Intergroup 0116 ( INT-0116 ) demonstrates strong persistent benefit from adjuvant radiochemotherapy . Toxicities , including second malignancies , appear acceptable , given the magnitude of RFS and OS improvement . LRF reduction may account for the majority of overall relapse reduction . Adjuvant radiochemotherapy remains a rational st and ard therapy for curatively resected gastric cancer with primaries T3 or greater and /or positive nodes BACKGROUND Surgical resection of adenocarcinoma of the stomach is curative in less than 40 percent of cases . We investigated the effect of surgery plus postoperative ( adjuvant ) chemoradiotherapy on the survival of patients with resectable adenocarcinoma of the stomach or gastroesophageal junction . METHODS A total of 556 patients with resected adenocarcinoma of the stomach or gastroesophageal junction were r and omly assigned to surgery plus postoperative chemoradiotherapy or surgery alone . The adjuvant treatment consisted of 425 mg of fluorouracil per square meter of body-surface area per day , plus 20 mg of leucovorin per square meter per day , for five days , followed by 4500 cGy of radiation at 180 cGy per day , given five days per week for five weeks , with modified doses of fluorouracil and leucovorin on the first four and the last three days of radiotherapy . One month after the completion of radiotherapy , two five-day cycles of fluorouracil ( 425 mg per square meter per day ) plus leucovorin ( 20 mg per square meter per day ) were given one month apart . RESULTS The median overall survival in the surgery-only group was 27 months , as compared with 36 months in the chemoradiotherapy group ; the hazard ratio for death was 1.35 ( 95 percent confidence interval , 1.09 to 1.66 ; P=0.005 ) . The hazard ratio for relapse was 1.52 ( 95 percent confidence interval , 1.23 to 1.86 ; P<0.001 ) . Three patients ( 1 percent ) died from toxic effects of the chemoradiotherapy ; grade 3 toxic effects occurred in 41 percent of the patients in the chemoradiotherapy group , and grade 4 toxic effects occurred in 32 percent . CONCLUSIONS Postoperative chemoradiotherapy should be considered for all patients at high risk for recurrence of adenocarcinoma of the stomach or gastroesophageal junction who have undergone curative resection Abstract Background To evaluate the safety and efficacy of a concurrent three-dimensional conformal radiotherapy ( 3D-CRT ) or intensity-modulated radiotherapy ( IMRT ) plus oxaliplatin , 5-fluorouracil and leucovorin ( FOLFOX ) regimen in completely resected gastric cancer patients with D2 lymph node dissection . Material s and methods Patients with stage IB – IIIC gastric cancer ( per the AJCC , 7th edition ) who had undergone R0 and D2 gastrectomy were recruited . Two cycles of FOLFOX with concurrent 3D-CRT or IMRT ( 50.4 Gy/28f ) were administered . One and an additional five cycles of FOLFOX were delivered before and after concurrent chemoradiotherapy , respectively . Primary endpoints were relapse-free survival ( RFS ) and overall survival ( OS ) , with adverse events as secondary endpoints . Results From 2008 to 2011 , 110 patients were evaluable . The 1- , 2- and 3-year RFS and OS were 86.2 , 72.2 , 67.8 and 94.7 , 87.2 , 77.6 % , respectively . On multivariate analysis , stage ( ≤IIIA vs. > IIIA ) was a statistically significant factor affecting both RFS and OS . Additionally , the T-category ( ≤T4a vs. = T4b ) was a statistically significant factor affecting only the RFS . The most commonly observed grade 3 or 4 adverse events were nausea and vomiting , decreased appetite , leukopenia/neutropenia and fatigue , each of which occurred in 14.5 , 11.8 , 9.1 and 6.4 % patients , respectively . Conclusions Adjuvant 3D-CRT/IMRT to a dose of 50.4 Gy/28f with concurrent FOLFOX is safe and effective in patients following radical gastrectomy Output:	No significant difference in the 3-year DFS rate was found between the IMRT and 3D-CRT groups . Grade 2–4 toxicities were similar between the IMRT and 3D-CRT groups . Conclusion The findings suggested that IMRT might be superior to 3D-CRT in treating patients with gastric cancer in terms of local control rates without increasing toxicity
MS22540	*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: Speed performance during gait initiation is known to be dependent on the capacity of the central nervous system to generate efficient anticipatory postural adjustments ( APA ) . According to the posturo-kinetic capacity ( PKC ) concept , any factor enhancing postural chain mobility and especially spine mobility , may facilitate the development of APA and thus speed performance . “ Spinal Manipulative Therapy High-Velocity , Low-Amplitude ” ( SMT-HVLA ) is a healing technique applied to the spine which is routinely used by healthcare practitioners to improve spine mobility . As such , it may have a positive effect on the PKC and therefore facilitate gait initiation . The present study aim ed to investigate the short-term effect of thoracic SMT-HVLA on spine mobility , APA and speed performance during gait initiation . Healthy young adults ( n = 22 ) performed a series of gait initiation trials on a force plate before ( “ pre-manipulation ” condition ) and after ( “ post-manipulation ” condition ) a sham manipulation or an HVLA manipulation applied to the ninth thoracic vertebrae ( T9 ) . Participants were r and omly assigned to the sham ( n = 11 ) or the HVLA group ( n = 11).The spine range of motion ( ROM ) was assessed in each participant immediately after the sham or HVLA manipulations using inclinometers . The results showed that the maximal thoracic flexion increased in the HVLA group after the manipulation , which was not the case in the sham group . In the HVLA group , results further showed that each of the following gait initiation variables reached a significantly lower mean value in the post-manipulation condition as compared to the pre-manipulation condition : APA duration , peak of anticipatory backward center of pressure displacement , center of gravity velocity at foot-off , mechanical efficiency of APA , peak of center of gravity velocity and step length . In contrast , for the sham group , results showed that none of the gait initiation variables significantly differed between the pre- and post-manipulation conditions . It is concluded that HVLA manipulation applied to T9 has an immediate beneficial effect on spine mobility but a detrimental effect on APA development and speed performance during gait initiation . We suggest that a neural effect induced by SMT-HVLA , possibly mediated by a transient alteration in the early sensory-motor integration , might have masked the potential mechanical benefits associated with increased spine mobility STUDY DESIGN R and omized , blinded , controlled crossover trial . OBJECTIVE To determine if thrust joint manipulation ( TJM ) to the lumbar spine would result in changes to the resting and contraction thickness of transversus abdominis ( TrA ) in healthy individuals . BACKGROUND Recent studies have demonstrated an immediate decrease in resting thickness and an increase in contraction thickness in TrA following lumbar TJM in patients with low back pain ( LBP ) who met a clinical prediction rule ( CPR ) for spinal manipulation . This observed phenomenon has not been investigated in healthy individuals . METHODS Thirty-five healthy participants were r and omly assigned to receive a TJM or sham manipulation treatment . All participants received instruction on how to produce an isolated concentric contraction of the TrA that involved visual ultrasound imaging biofeedback . Data were analyzed using ultrasound imaging to measure changes in thickness of the TrA at rest and during contraction , following the administration of each treatment . RESULTS There were no interactions observed between treatment and time for TrA muscle thickness at rest ( P = .351 ) and during the contracted state ( P = .761 ) . CONCLUSION Our results indicate that TJM to the lumbar spine does not appear to affect the resting or contraction thickness of TrA in healthy individuals . These findings are in contrast to previous research in which patients with LBP who met a CPR demonstrated an immediate decrease in resting thickness and an increase in contraction thickness in TrA following lumbar TJM Purpose The primary purpose of this study was to investigate whether a single session of spinal manipulation ( SM ) increases strength and cortical drive in the lower limb ( soleus muscle ) of elite Taekwondo athletes . Methods Soleus-evoked V-waves , H-reflex and maximum voluntary contraction ( MVC ) of the plantar flexors were recorded from 11 elite Taekwondo athletes using a r and omized controlled crossover design . Interventions were either SM or passive movement control . Outcomes were assessed at pre-intervention and at three post-intervention time periods ( immediate post , post 30 min and post 60 min ) . A multifactorial repeated measures ANOVA was conducted to assess within and between group differences . Time and session were used as factors . A post hoc analysis was carried out , when an interactive effect was present . Significance was set at p ≤ 0.05 . Results SM increased MVC force [ F(3,30 ) = 5.95 , p < 0.01 ] , and V-waves [ F(3,30 ) = 4.25 , p = 0.01 ] over time compared to the control intervention . Between group differences were significant for all time periods ( p < 0.05 ) except for the post60 force measurements ( p = 0.07 ) . Conclusion A single session of SM increased muscle strength and corticospinal excitability to ankle plantar flexor muscles in elite Taekwondo athletes . The increased MVC force lasted for 30 min and the corticospinal excitability increase persisted for at least 60 min We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a r and omised controlled trial . To develop the framework , we undertook a Delphi survey ; ran an open meeting at a trial methodology conference ; conducted a review of definitions outside the health research context ; consulted experts at an international consensus meeting ; and review ed 27 empirical pilot or feasibility studies . We initially adopted mutually exclusive definitions of pilot and feasibility studies . However , some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions . Their viewpoint was supported by definitions outside the health research context , the use of the terms ‘ pilot ’ and ‘ feasibility ’ in the literature , and participants at the international consensus meeting . In our framework , pilot studies are a subset of feasibility studies , rather than the two being mutually exclusive . A feasibility study asks whether something can be done , should we proceed with it , and if so , how . A pilot study asks the same questions but also has a specific design feature : in a pilot study a future study , or part of a future study , is conducted on a smaller scale . We suggest that to facilitate their identification , these studies should be clearly identified using the terms ‘ feasibility ’ or ‘ pilot ’ as appropriate . This should include feasibility studies that are largely qualitative ; we found these difficult to identify in electronic search es because research ers rarely used the term ‘ feasibility ’ in the title or abstract of such studies . Investigators should also report appropriate objectives and methods related to feasibility ; and give clear confirmation that their study is in preparation for a future r and omised controlled trial design ed to assess the effect of an intervention OBJECTIVE The purpose of this study was to measure the impact of midlumbar spinal manipulation on asymptomatic cyclist sprint performance and hip flexibility . METHODS Twelve cyclists were equally r and omized into an AB : BA crossover study design after baseline testing . Six participants were in the AB group , and 6 were in the BA group . The study involved 1 week of rest in between each of the 3 tested conditions : baseline testing ( no intervention prior to testing ) , condition A ( bilateral midlumbar spine manipulation prior to testing ) , and condition B ( sham acupuncture prior to testing , as a control ) . Testing was blinded and involved a sit- and -reach test followed by a 0.5-km cycle ergometer sprint test against 4-kp resistance . Outcome measures were sit- and -reach distance , time to complete 0.5 km , maximum heart rate , and rating of perceived exertion . An additional 8 cyclists were recruited and used as a second set of controls that engaged in 3 testing sessions without any intervention to track test acclimation . An analysis of variance was used to compare dependent variables under each of the 3 conditions for the experimental group and control group # 1 , and a repeated- measures analysis of variance was used to analyze test acclimation in control group # 2 . RESULTS Lumbar spine manipulation did not demonstrate statistically significant between-group changes in sit- and -reach ( P = .765 ) , 0.5-km sprint performance time ( P = .877 ) , maximum exercise heart rate ( P = .944 ) , or rating of perceived exertion ( P = .875 ) . CONCLUSIONS The findings of this preliminary study showed that midlumbar spinal manipulation did not improve hip flexibility or cyclist power output of asymptomatic participants compared with an acupuncture sham and no-treatment control groups OBJECTIVE The objective of this study was to perform an investigation evaluating if cervical spinal manipulative therapy ( SMT ) can increase grip strength on judo athletes in a top 10 national-ranked team . METHODS A single-blinded , prospect i ve , comparative , pilot , r and omized , clinical trial was performed with 18 athletes of both sexes from a judo team currently competing on a national level . The athletes were r and omly assigned to 2 groups : chiropractic SMT and sham . Three interventions were performed on each of the athletes at different time points . Force measurements were obtained by a hydraulic dynamometer immediately before and after each intervention at the same period before training up to 3 weeks with at least 36 hours between interventions . RESULTS Analysis of grip strength data revealed a statistically significant increase in strength within the treatment group after the first intervention ( 6.95 % right , 12.61 % left ) as compared with the second ( 11.53 % right , 17.02 % left ) and the third interventions ( 10.53 % right , 16.81 % left ) . No statistically significant differences were found in grip strength comparison within the sham group . Overall differences in strength were consistently significant between the study groups ( P = .0025 ) . CONCLUSION The present study suggests that the grip strength of national level judo athletes receiving chiropractic SMT improved compared to those receiving sham Background The most utilized soccer kicking method is the instep kicking technique . Decreased motion in spinal joint segments results in adverse biomechanical changes within in the kinematic chain . These changes may be linked to a negative impact on soccer performance . This study tested the immediate effect of lumbar spine and sacroiliac manipulation alone and in combination on the kicking speed of uninjured soccer players . Methods This 2010 prospect i ve , pre-post experimental , single-blinded ( subject ) required forty asymptomatic soccer players , from regional premier league teams , who were purposively allocated to one of four groups ( based on the evaluation of the players by two blinded motion palpators ) . Segment dysfunction was either localized to the lumbar spine ( Group 1 ) , sacroiliac joint ( Group 2 ) , the lumbar spine and sacroiliac joint ( Group 3 ) or not present in the sham laser group ( Group 4 ) . All players underwent a st and ardized warm-up before the pre- measurements . Manipulative intervention followed after which post- measurements were completed . Measurement outcomes included range of motion changes ( digital inclinometer ) ; kicking speed ( Speed Trac ™ Speed Sport Radar ) and the subjects ’ perception of a change in kicking speed . SPSS version 15.0 was used to analyse the data , with repeated measures ANOVA and a p-value < 0.05 ( CI 95 % ) . Results Lumbar spine manipulation result ed in significant range of motion increases in left and right rotation . Sacroiliac manipulation result ed in no significant changes in the lumbar range of motion . Combination manipulative interventions result ed in significant range of motion increases in lumbar extension , right rotation and right SI joint flexion . There was a significant increase in kicking speed post intervention for all three manipulative intervention groups ( when compared to sham ) . A significant correlation was seen between Likert based-scale subjects ’ perception of change in kicking speed post intervention and the objective results obtained . Conclusions This pilot study showed that lumbar spine manipulation combined with SI joint manipulation , result ed in an effective intervention for short-term increases in kicking speed/performance . However , the lack of an a priori analysis , a larger sample size and an unblinded outcome measures assessor requires that this study be repeated , addressing these concerns and for these outcomes to be vali date OBJECTIVE The purpose of this study was to examine the immediate effects of spinal manipulative therapy ( SMT ) on trunk proprioception in subjects with asymptomatic chronic low back pain ( CLBP ) and determine if those effects lasted 1 week . METHODS This unbalanced r and omized controlled crossover design examined 33 subjects with CLBP . Proprioception was tested via joint position sense , threshold to detect passive motion ( TTDPM ) , direction of motion ( DM ) , and force reproduction . Each subject received lumbar manipulation or a sham procedure followed by proprioception retest . This procedure was repeated 1 week later using the opposing treatment . Subjects receiving SMT in the second session returned a third time receiving the sham procedure again . RESULTS Spinal manipulative therapy produced an effect for TTDPM in the manipulation first group ( P = .008 ) , the sham procedure produced an effect for joint position sense in the sham first group ( P = .005 ) . Spinal manipulative therapy had a 1-week effect for the manipulation first group ( P = .006 ) . No effect was noted for either DM or force reproduction . CONCLUSIONS Results suggest SMT had minimal immediate effect on trunk proprioception . The effects noted occurred in session 1 , implicating learning as a potential source . Learning , from repetitive proprioception training , may enhance neuromuscular control in subjects with CLBP before the use of therapeutic exercise . Subjects showed smaller deficits than previously reported for TTDPM or DM , suggesting proprioception deficits may correlate with pain level OBJECTIVE This study investigates the effect of chiropractic treatment on hip joint extension ability Output:	Sport-specific studies show no effect of SMT except for a small increase in basketball free-throw accuracy . Conclusion The preponderance of evidence suggests that SMT in comparison to sham or other interventions does not enhance performance-based outcomes in asymptomatic adult population . In the few studies suggesting a positive immediate effect , the importance of such change is uncertain .
MS22541	*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 the present prospect i ve , noncomparative , multicenter study was assess the safety and efficacy of gentamicin and doxycycline therapy for human brucellosis . In the first part of the study , a cohort of 17 patients received 100 mg of doxycycline ( or 50 mg/kg of body weight per day if the body weight was < 40 kg ) orally every 12 h for 45 days ( cohort 1 ) . In the second part of the study a subsequent cohort of 35 patients was treated with doxycycline at the same dosage for 30 days ( cohort 2 ) . All patients were treated intramuscularly with gentamicin at 240 mg ( or 5 mg/kg per day if the body weight was < 50 kg ) once daily for the first 7 days . Both cohorts showed a favorable response during therapy , and there were no therapeutic failures . Relapse was noted in 1 ( 5.9 % ; 95 % confidence interval [ 95 % CI ] , 0.15 to 28.7 % ) of the 17 patients in cohort 1 and in 8 ( 22.9 % ; 95 % CI , 10.4 to 40.1 % ) of the 35 patients in cohort 2 . Nineteen patients ( 36.5 % ; 95 % CI , 23.6 to 51.0 % ) had adverse effects , with no differences between cohorts , and no patients had a treatment-limiting adverse effect . The study indicates that the combination of doxycycline for 45 days and gentamicin for 7 days is an effective and well-tolerated therapy for human brucellosis . The relapse rates obtained with doxycycline treatment for 30 days appear to be higher than those obtained with doxycycline treatment for 45 days Background The combination therapies recommended by the World Health Organization for treatment of brucellosis are doxycycline plus rifampicin or doxycycline plus streptomycin . Although highly successful results have been obtained with these two regimens , relapse rates as high as 14.4 % . The most effective and the least toxic chemotherapy for human brucellosis is still undetermined . The aim of the present study was to investigate the efficacy , adverse effects and cost of ofloxacin plus rifampicin therapy , and doxycycline plus rifampicin therapy and evaluate in the treatment of brucellosis . Methods The open trial has been carried out prospect ively by the two medical centers from December 1999 to December 2001 in Duzce region Turkey . The diagnosis was based on the presence of signs and symptoms compatible with brucellosis including a positive agglutination titre ( ≥1/160 ) and /or a positive culture . Doxycycline and rifampicin group consisted of 14 patients who were given doxycycline 200 mg/day plus rifampicin 600 mg/day during 45 days and this group Ofloxacin plus rifampicin group was consisted of 15 patients who were given ofloxacin 400 mg/day plus rifampicin 600 mg/day during 30 days . Results Regarding clinical and /or demographic characteristics no significant difference was found between two groups of patients that underwent two different therapeutic regimens . At the end of the therapy , two relapses were seen in both groups ( p = 0.695 ) . Although duration of therapy was two weeks shorter in group treated with rifampicin plus ofloxacin , the cure rate was similar in both groups of examinees . Fever dropped more rapidly in the group that treated with rifampicin plus ofloxacin , 74 ± 30 ( ranges 48–216 ) vs. 106 ± 26 ( ranges 48–262 ) hours ( p = 0.016 ) . Conclusions Ofloxacin plus rifampicin therapy has advantages of shorter treatment duration and provided shorter course of fever with treatment than in doxycycline plus rifampicin therapy . However , cost of ofloxacin plus rifampicin treatment is higher than doxycycline plus rifampicin treatment . Because of the similar effects , adverse effects and relapses rates between two regimens , we still advice doxycycline plus rifampicin for the treatment of brucellosis for countries , which have limited re sources McDevitt , D. G. (1970).Brit . J. industr . Med.,27 , 67 - 71 . Ampicillin in the treatment of brucellosis : A controlled therapeutic trial . A controlled therapeutic trial has been carried out with ampicillian in the treatment of brucellosis . Sixty-eight people , veterinary surgeons or their unqualified assistants , with serological evidence of brucella antibodies measured by the anti-human globulin ( Coombs ) test and the complement-fixation test , some of whom had symptoms consistent with a diagnosis of brucellosis , were treated in two r and om groups . One group was given ampicillin , 1 g. four times a day for 28 days ; the other took a placebo in identical capsules for the same period . The response to treatment was gauged by subjective improvement in symptoms four weeks after its completion and by serological improvement after four months . Fifty-four people completed the trial . There was no evidence that ampicillin was any more effective than the placebo in treatment , either symptomatically or serologically , but 25 % of the people in both treatment groups reported subjective symptomatic improvement . It is suggested , therefore , that subjective improvement alone is an inadequate criterion for assessing response to treatment in culturally unproven brucellosis , and that , because of this , current conventional therapies may require critical revaluation . Similarly , a subjective therapeutic response can not be relied upon for diagnostic confirmation in a patient in whom the diagnosis is uncertain A r and omized prospect i ve , pilot study was performed to compare the efficacy of oral ciprofloxacin ( 750 mg or 1000 mg bd ) with st and ard oral antimicrobial therapy ( rifampicin plus doxycycline ) in the treatment of acute infection with Brucella melitensis . All antimicrobial drugs were administered for 42 days . Although all patients responded rapidly , five of the six patients receiving ciprofloxacin relapsed following cessation of therapy . There were no relapses among the patients who received doxycycline/rifampicin . Despite its in-vitro activity against B. melitensis ( MIC 0.5 mg/l ) , ciprofloxacin , administered twice daily , does not appear to constitute adequate therapy for acute brucellosis Effectiveness and therapeutic value of the doxycycline plus streptomycin and doxycycline plus rifampin schedules of treatment of human brucellosis have been assessed by carrying out a prospect i ve study on 111 patients r and omly distributed into two groups . Patients in group A were treated with doxycycline plus streptomycin sulphate and those in group B with doxycycline plus rifampin . The temperature of all patients reverted to normal , and 54 patients from group A ( 91.6 % ) and 45 from group B ( 86.5 % ) achieved total recovery with a single therapeutic cycle . Two therapeutic failures and 3 relapses in group A ( 8.4 % ) and 7 relapses in group B ( 13.46 % ) were observed . The tolerance to both regimens was good . Although the combination doxycycline plus rifampin offers a more convenient oral administration , in the light of these results , until more extensive research is carried out , it should be considered as an alternative rather than a first choice in the treatment of human brucellosis Background The optimal treatment regimen and duration of the therapy is still controversial in spinal brucellosis . The aim of this study is to compare the efficacy , adverse drug reactions , complications and cost of ciprofloxacin plus rifampicin versus doxycycline plus streptomycin in the treatment of spinal brucellosis . Methods The patients diagnosed as spinal brucellosis between January 2002 to December 2004 were enrolled into the study . Patients were enrolled into the two antimicrobial therapy groups ( doxycycline plus streptomycin vs. ciprofloxacin plus rifampicin ) consecutively . For the cost analysis of the two regimens , only the cost of antibiotic therapy was analysed for each patient . Results During the study period , 31 patients with spinal brucellosis were enrolled into the two antimicrobial therapy groups . Fifteen patients were included in doxycycline plus streptomycin group and 16 patients were included in ciprofloxacin plus rifampicin group . Forty-two levels of spinal column were involved in 31 patients . The most common affected site was lumbar spine ( n = 32 , 76 % ) and involvement level was not different in two groups . Despite the disadvantages ( older age , more prevalent operation and abscess formation before the therapy ) of the patients in the ciprofloxacin plus rifampicin group , the duration of the therapy ( median 12 weeks in both groups ) and clinical response were not different from the doxycycline plus streptomycin . The cost of ciprofloxacin plus rifampicin therapy was 1.2 fold higher than the cost of doxycycline plus streptomycin therapy . Conclusion Classical regimen ( doxycycline plus streptomycin ) , with the appropriate duration ( at least 12 weeks ) , is still the first line antibiotics and alternative therapies should be considered when adverse drug reactions were observed OBJECTIVE To compare the effectiveness of doxycycline-rifampin ( DR ) combination therapy with that of the classic doxycycline-streptomycin ( DS ) combination in patients with brucellosis . DESIGN A r and omized , double-blind study , with a mean follow-up of 15.7 months . SETTING A 1000-bed teaching hospital in Barcelona , Spain . PATIENTS Ninety-five patients ( 68 men and 27 women ; mean age , 39 years ) diagnosed with brucellosis on the basis of both clinical and serologic findings ; 81 of these patients had blood cultures positive for Brucella melitensis . INTERVENTIONS Forty-four patients received doxycycline , 100 mg every 12 hours , and rifampin , 15 mg/kg body weight per day in a single morning dose , for 45 days ; 51 patients received the same dose of doxycycline for 45 days plus streptomycin , 1 g/d for 15 days . MAIN OUTCOME MEASURES Therapeutic failure and relapse during the follow-up period . RESULTS The mean time to defervescence was 4.2 days for the DR group and 3.2 days for the DS group ( P greater than 0.2 ) . The actuarial probability of therapeutic failure or relapse at 12 months of follow-up ( Kaplan-Meier ) was 14.4 % in the DR group and 5.9 % in the DS group ( difference , 8.5 % ; 95 % Cl , -4.8 % to 21.6 % ; P greater than 0.2 ) . All three patients with spondylitis in the DR group failed therapy compared with one of four patients in the DS group . Excluding patients with spondylitis , the actuarial failure rate was 4.9 % and 4.3 % in the DR and DS groups , respectively , at 12 months of follow-up ( difference , 0.6 % ; Cl , -8.1 % to 9.4 % ; P greater than 0.2 ) . CONCLUSIONS Doxycycline-rifampin combination therapy for 45 days is as effective as the classic DS combination in most patients with brucellosis ; however , DR therapy might be less effective in those patients with spondylitis Abstract Brucellosis , a zoonosis with worldwide distribution , is a systemic infection and still an important public health problem in Turkey . The best antimicrobial combination and schedule for the treatment of brucellosis with spondylitis has not yet been clearly determined . In a prospect i ve and r and omized study , we compared the efficacy of five antimicrobial regimens for treatment of 102 patients with lumbar brucellar spondylitis . Patients were r and omly assigned to receive antimicrobial combination therapy . Twenty patients received streptomycin 1 g/day intramuscularly for 15 days and tetracycline-HCl , 500 mg every 6 h orally for 45 days ( ST ) , 21 patients received streptomycin 1 g/day i.m . for 15 days and doxycycline 100 mg every 12 h orally for 45 days ( SD ) , 20 patients received doxycycline 100 mg every 12 h orally for 45 days and rifampicin 15 mg/kg per day in a single morning dose orally for 45 days ( DR ) , 19 patients received ofloxacin , 200 mg every 12 h orally for 45 days and rifampicin 15 mg/kg per day in a single morning dose orally for 45 days ( OR ) , and 22 patients received streptomycin 1 g/day i.m . for 15 days and doxycycline 100 mg every 12 h orally for 45 days plus rifampicin 15 mg/kg per day in a single morning dose orally for 45 days ( SDR ) . Initial therapeutic failure occurred in 2 patients ( 10 % ) in the ST regimen group , Output:	Doxycycline ( six weeks ) plus streptomycin ( two or three weeks ) regimen is more effective regimen than doxycycline plus rifampicin ( six weeks ) regimen . Since it needs daily intramuscular ( IM ) injection , access to care and cost are important factors in deciding between two choices . Quinolone plus rifampicin ( six weeks ) regimen is slightly better tolerated than doxycycline plus rifampicin , and low quality evidence did not show any difference in overall effectiveness
MS22542	*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 determine whether presenting test performance characteristics influences clinical management . DESIGN Two question naire-based , r and omized controlled trials . SETTING Mailed surveys with 2 clinical vignettes . PARTICIPANTS R and omly selected US pediatricians ( N=1502 ) . INTERVENTION Vignette-specific , r and omly assigned test information : no additional information ( control ) , test characteristics ( TC ) , or TC defined . In the pertussis vignette , the TC group received the direct fluorescent antibody test 's sensitivity and specificity , and the TC defined group received the same information with definitions . In the urinalysis vignette , the TC group received the false-positive rate of persistent microhematuria in predicting renal disease , and the TC defined group received a definition of this information . MAIN OUTCOME MEASURES In the pertussis vignette , diagnostic test choice and management of erythromycin therapy and hospital discharge plans . In the urinalysis vignette , serum laboratory testing and nephrology referral plans . RESULTS Six hundred fifty-three participants ( 49.5 % of those eligible ) returned completed surveys . In the pertussis vignette , significantly more of the TC ( 73 % ) and TC defined ( 71 % ) groups ordered the best-performing test than did controls ( 21 % ) ( P<.001 for both comparisons ) . Receiving test characteristics did not significantly affect erythromycin therapy or hospital discharge plans ( P > or=.40 ) . In the urinalysis vignette , the TC defined group referred to nephrology ( 30 % ) and checked laboratory tests ( 88 % ) significantly more often than did controls ( 19 % , P=.01 ; 78 % , P=.01 , respectively ) , but the TC and control groups ' testing and referral plans did not differ significantly ( 22 % vs 19 % , P=.36 ; 75 % vs 78 % , P=.48 , respectively ) . CONCLUSION Providing test performance characteristics influenced certain clinical decisions , sometimes in unexpected ways Abstract Objective : To assess the extent to which different forms of summarising diagnostic test information influence general practitioners ' ability to estimate disease probabilities . Design : Controlled question naire study . Setting : Three Swiss conferences in continuous medical education . Participants : 263 general practitioners . Intervention : Question naire with multiple choice questions about terms of test accuracy and a clinical vignette with the results of a diagnostic test described in three different ways ( test result only , test result plus test sensitivity and specificity , test result plus the positive likelihood ratio presented in plain language ) . Main outcome measures : Doctors ' knowledge and application of terms of test accuracy and estimation of disease probability in the clinical vignette . Results : The correct definitions for sensitivity and predictive value were chosen by 76 % and 61 % of the doctors respectively , but only 22 % chose the correct answer for the post-test probability of a positive screening test . In the clinical vignette doctors given the test result only overestimated its diagnostic value ( median attributed likelihood ratio (aLR)=9.0 , against 2.54 reported in the literature ) . Providing the scan 's sensitivity and specificity reduced the overestimation ( median aLR=6.0 ) but to a lesser extent than simple wording of the likelihood ratio ( median aLR=3.0 ) . Conclusion : Most general practitioners recognised the correct definitions for sensitivity and positive predictive value but did not apply them correctly . Conveying test accuracy information in simple , non-technical language improved their ability to estimate disease probabilities accurately . What is already known on this topic Many doctors confuse the sensitivity of clinical tests and their positive predictive value Doctors tend to overestimate information derived from such tests and underestimate information from a patient 's clinical history Most primary research on diagnostic accuracy is reported using sensitivity and specificity or likelihood ratios What this study adds In a cohort of experienced Swiss general practitioners most were unable to interpret correctly numerical information on the diagnostic accuracy of a screening test When presented with a positive result alone they grossly overestimated its value Adding information on the test 's sensitivity and specificity moderated these overestimates , and expressing the same numerical information as a positive likelihood ratio in simple , non-technical language brought the estimates still closer to their true Abstract Objective To investigate the accuracy of interpretation of probabilistic screening information by different stakeholder groups and whether presentation as frequencies improves accuracy . Design Between participants experimental design ; participants responded to screening information embedded in a scenario . Setting Regional maternity service and national conferences and training days . Participants 43 pregnant women attending their first antenatal appointment in a regional maternity service ; 40 companions accompanying the women to their appointments ; 42 midwives ; 41 obstetricians . Participation rates were 56 % , 48 % , 89 % , and 71 % respectively . Measures Participants estimated the probability that a positive screening test result meant that a baby actually had Down 's syndrome on the basis of all the relevant information , which was presented in a scenario . They were r and omly assigned to scenarios that presented the information in percentage ( n = 86 ) or frequency ( n = 83 ) format . They also gave basic demographic information and rated their confidence in their estimate . Results Most responses ( 86 % ) were incorrect . Obstetricians gave significantly more correct answers ( although still only 43 % ) than either midwives ( 0 % ) or pregnant women ( 9 % ) . Overall , the proportion of correct answers was higher for presentation as frequencies ( 24 % ) than for presentation as percentages ( 6 % ) , but further analysis showed that this difference occurred only in responses from obstetricians . Many health professionals were confident in their incorrect responses . Conclusions Most stakeholders in pregnancy screening draw incorrect inferences from probabilistic information , and health professionals need to be aware of the difficulties that both they and their patients have with such information . Moreover , they should be aware that different people make different mistakes and that ways of conveying information that help some people will not help others BACKGROUND Underst and ing pre-test probability and baseline risks helps to interpret the results of diagnostic tests and the benefits of treatment , but how good is the underst and ing of these concepts ? OBJECTIVES Our aim was to assess the ability of GPs and consultant physicians to make accurate estimates and underst and the application of pre-test probability and baseline risk for two common clinical conditions . METHODS A two-stage question naire survey based on case scenarios of patients with angina and congestive heart failure was carried out of 202 physicians , r and omly selected from the members of the Royal College of Physicians in the NW of Engl and , 205 GPs r and omly chosen from the practice list of the NW Health Authorities and 128 MRCGP examiners attending an examiners meeting . A total of 115 , 106 and 81 members of these groups , respectively , responded to the first stage , and 44 , 46 and 64 to the second . The main outcome measures were the stated likelihood of true ischaemic heart disease ( IHD ) being present and the predicted 1-year mortality ; the impact of changing prevalence and baseline risk on these results ; and interpretation of different methods of risk presentation . RESULTS Estimates of pre-test probability of IHD being present ranged from 5 to 100 % and of baseline risk of 1-year mortality from 0 to 86 % . More GP examiners and consultant physicians understood the impact of increasing age on the test result than did the r and om sample of GPs . A majority of each group correctly said that increasing age would reduce the number needed to treat ( NNT ) . Presentation of benefit as relative risk reduction was a greater stimulus to starting treatment than the NNT or measures of population impact . CONCLUSION Clinicians should collect data to allow a better knowledge of the likelihood of disease and of baseline risk in their patient population s. Methods to increase the underst and ing of the influence of pre-test probability on diagnostic test results and of how to quantify and demonstrate the impact of the benefit of interventions should be explored Abstract Objectives : To determine how medical students apply research evidence that varies in validity of methods and importance of results to a clinical decision . Design : Students examined a st and ardised patient with a whiplash injury , decided whether to order a cervical spine radiograph , and rated their confidence in their decision . They then read one of four r and omly assigned variants of a structured abstract from a study of a decision rule that argued against such a procedure in this patient . Variants factorially combined two levels of validity of methods ( prospect i ve cohort or chart review ) with two levels of importance of results ( high sensitivity or high specificity rule ) . After reading the abstract , students repeated their choice and rated their confidence . Setting : Academic medical centre in the United States . Participants : 164 graduating medical students . Main outcome measures : Proportion of students in each group whose beliefs shifted or stayed the same . Results : When abstract s were of low importance students were more likely to shift their beliefs in favour of radiography , which was not supported by the evidence ( odds ratio 3.42 , 95 % confidence interval 1.10 to 10.66 ) . Neither method ological validity nor the interaction between validity and importance influenced decision shift . Few students acquired all necessary clinical data from the patient . Conclusions : Although the students could apply concepts of diagnostic testing , greater focus is needed on appraisal of validity and application of evidence to a particular patient . What is already known on this topic Evidence based medicine is increasingly emphasised and taught in medical schools Few studies have assessed the ability of physicians to apply literature findings to clinical decisions What this paper adds In making decisions about ordering investigations during a st and ardised patient exam students were sensitive to the importance of results This effect was not moderated by validity of the study that produced the results or whether the students had collected enough information to apply the Context There are several ways to present information about the accuracy of diagnostic tests . Contribution In this vignette-based study , 183 physicians read 6 scenarios that included patients ' presenting symptoms , risk profiles , and test results . Physicians were r and omly assigned to view information about test accuracy as sensitivity and specificity , a likelihood ratio , or an inexact graphic of the likelihood ratio . In general , the groups estimated similar post-test probabilities of disease regardless of how diagnostic accuracy was presented . Implication s This preliminary work suggests some physicians may interpret sensitivity and specificity and likelihood ratio information in a similar manner . The Editors Diagnostic tests are used to reduce uncertainty about the presence or absence of an illness . The informativeness of a diagnostic test , usually expressed as its sensitivity and specificity or as a likelihood ratio , determines how much the illness probability changes from the pretest to the post-test situation . The change in illness probability can be calculated using the Bayes theorem , which combines the illness probability before testing with the information derived from the test ( 1 ) . Few physicians use this formal approach to weigh the informativeness of diagnostic test results ( 2 ) and , perhaps as a result , make mistakes when asked to use it ( 3 , 4 ) . Many investigators advocate the use of likelihood ratios ( 5 - 8 ) . However , the effect of different presentation formats for diagnostic accuracy on post-test probability estimates has not been rigorously tested . We conducted a r and omized study to see if physicians ' estimates about illness probability more closely reflect estimates determined by the Bayes theorem when diagnostic information is presented as sensitivity and specificity estimates , a likelihood ratio , or an inexact numerical graphic . Methods We r and omly assigned experienced specialists in family and internal medicine attending a continuing medical education conference to complete 1 of 3 self-administered question naires that presented vignettes representative of scenarios commonly encountered early in the diagnostic work-up . The vignettes differed only in how diagnostic test accuracy was presented . The question naires were sealed within 576 envelopes that had been r and omized in 32 blocks of 18 to avoid order effects ( 6 different vignette orders for each of the 3 test accuracy presentation formats ) . We distributed the envelopes before participants entered the lecture hall so that we could not predict which participant received which envelope , thus concealing the r and omization . The moderator of the lecture ( which was unrelated to material presented in the vignettes ) advised those present to complete the question naire during small breaks or at the end of the lecture . We collected 183 question naires 15 minutes after the lecture and excluded 5 question naires that were sent to us later . The question naires asked participants to assess 6 clinical patient profiles and to estimate the probability of illness , specifying a percentage between 0 % and 100 % , for each scenario . With the exception of the chronic obstructive pulmonary disease vignette , all patient vignettes consisted of a description of presenting symptoms , additional clinical facts , and a risk profile ( Appendix Table ) . In the chronic obstructive pulmonary disease vignette , no presenting symptom but only the risk profile was given . For each vignette , we then gave the result of a diagnostic test commonly used in clinical practice and the test 's accuracy derived from the literature , presented as sensitivities and specificities ( group 1 ) , as a positive or negative likelihood ratio ( group 2 ) , or as an inexact numerical graphical format ( group 3 ) . Using the test result and its diagnostic accuracy , participants were then invited to estimate the post-test probability . As shown in the Appendix Table , we varied the informativeness of the diagnostic tests for both negative and positive results by presenting examples of weak ( vignettes 1 and 4 ) , intermediate ( vignettes 2 and 5 ) , and strong ( vignettes 3 and 6 ) test accuracies . Sensitivities and specificities were given as percentages to group 1 . In group 2 , the positive or negative likelihood ratios were presented as a numerical value and described in nontechnical language . For example , the description of the d-dimer test 's positive likelihood ratio of 1.7 in patients with high probability of pulmonary embolism ( 9 ) was additionally described as in patients with pulmonary embolism , a positive test result is found almost twice as often as in patients without pulmonary embolism . For group 3 , we depicted an inexact numerical presentation with a simple graphic of 5 circles ( ) . We darkened an increasing number of circles to correspond with increasing positive likelihood ratios or Output:	Results Participants unfamiliar with the design and methodology of DTARs found the review s largely inaccessible and experienced a range of difficulties stemming mainly from the mismatch between background knowledge and level of explanation provided in the text . Experience with systematic review s of interventions did not guarantee better underst and ing and , in some cases , led to confusion and misinterpretation . These difficulties were further exacerbated by poor layout and presentation , which affected even those with relatively good knowledge of DTARs and had a negative impact not only on their underst and ing of the review s but also on their motivation to engage with the text . Comparison between the readings of the three review s showed that more accessible presentation , such as presenting the results as natural frequencies , significantly increased participants ’ underst and ing . Conclusions The study demonstrates that authors and editors should pay more attention to the presentation as well as the content of Cochrane DTARs , especially if the reports are aim ed at readers with various levels of background knowledge and experience . It also raises the question as to the anticipated target audience of the reports and suggests that different groups of healthcare decision-makers may require different modes of presentation
MS22543	*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 To develop a checklist of items measuring the quality of reports of r and omized clinical trials ( RCTs ) assessing nonpharmacological treatments ( NPTs ) . STUDY DESIGN AND SETTING The Delphi consensus method was used to select and reduce the number of items in the checklist . A total of 154 individuals were invited to participate : epidemiologists and statisticians involved in the field of methodology of RCTs ( n = 55 ) , members of the Cochrane Collaboration ( n = 41 ) , and clinicians involved in planning NPT clinical trials ( n = 58 ) . Participants ranked on a 10-point Likert scale whether an item should be included in the checklist . RESULTS Fifty-five experts ( 36 % ) participated in the survey . They were experienced in systematic review s ( 68 % were involved in the Cochrane Collaboration ) and in planning RCTs ( 76 % ) . Three rounds of the Delphi method were conducted to achieve consensus . The final checklist contains 10 items and 5 subitems , with items related to the st and ardization of the intervention , care provider influence , and additional measures to minimize the potential bias from lack of blinding of participants , care providers , and outcome assessors . CONCLUSIONS This tool can be used to critically appraise the medical literature , design NPT studies , and assess the quality of trial reports included in systematic review To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results 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 The EBN users ’ guide in the previous issue of Evidence -Based Nursing outlined the primary and secondary questions for evaluating studies of healthcare interventions . One of the primary questions for assessing the validity of a study ’s findings is whether the assignment of patients to treatments was r and omised and whether r and omisation was concealed . One of the secondary questions is whether patients , clinicians , outcome assessors , and data analysts were unaware of ( blinded to or masked from ) patient allocation . Beginning with the October 1999 issue of Evidence -Based Nursing , allocation concealment and blinding have been given more attention . The “ design ” section of abstract s of r and omised trials now includes a statement of whether r and omisation was concealed from those responsible for entering patients into trials , and who was blinded to treatment allocation during the trials . These additional specifications provide readers with more information to judge the internal validity of trials . In this editorial , the background and rationale for these decisions are addressed CONTEXT The Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement was developed to help improve the quality of reports of r and omized controlled trials ( RCTs ) . To date , a paucity of data exists regarding whether it has achieved this goal . OBJECTIVE To determine whether use of the CONSORT statement is associated with improvement in the quality of reports of RCTs . DESIGN AND SETTING Comparative before- and -after evaluation in which reports of RCTs published in 1994 ( pre-CONSORT ) were compared with RCT reports from the same journals published in 1998 ( post-CONSORT ) . We included 211 reports from BMJ , JAMA , and The Lancet ( journals that adopted CONSORT ) as well as The New Engl and Journal of Medicine ( a journal that did not adopt CONSORT and was used as a comparator ) . MAIN OUTCOME MEASURES Number of CONSORT items included in a report , frequency of unclear reporting of allocation concealment , and overall trial quality score based on the Jadad scale , a 5-point quality assessment instrument . RESULTS Compared with 1994 , the number of CONSORT checklist items in reports of RCTs increased in all 4 journals in 1998 , and this increase was statistically significant for the 3 adopter journals ( pre-CONSORT , 23.4 ; mean change , 3.7 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) . The frequency of unclear reporting of allocation concealment decreased for each of the 4 journals , and this change was statistically significant for adopters ( pre-CONSORT , 61 % ; mean change , -22 % ; 95 % CI , -38 % to -6 % ) . Similarly , 3 of the 4 journals showed an improvement in the quality score for reports of RCTs , and this increase was statistically significant for adopter journals overall ( pre-CONSORT , 2.7 ; mean change , 0.4 ; 95 % CI , 0.1 - 0.8 ) . CONCLUSION Use of the CONSORT statement is associated with improvements in the quality of reports of RCTs A system has been constructed to evaluate the design , implementation , and analysis of r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials Background : The purpose of this study was threefold : ( 1 ) to determine the scientific quality of published r and omized trials in the American Volume of The Journal of Bone and Joint Surgery from 1988 through 2000 , ( 2 ) to identify predictors of study quality , and ( 3 ) to evaluate inter-rater agreement in the scoring of study quality with use of a simple scale . Methods : H and search es of The Journal of Bone and Joint Surgery were conducted in duplicate to identify r and omized clinical trials . Of 2468 studies identified , seventy-two ( 2.9 % ) met all eligibility criteria . Two investigators each assessed the quality of the study under blinded conditions and abstract ed relevant data . Results : The mean score ( and st and ard error ) for the quality of the seventy-two r and omized trials was 68.1 % ± 1.6 % ; 60 % ( forty-three ) scored < 75 % . Drug trials had a significantly higher mean quality score than did surgical trials ( 72.8 % compared with 63.9 % , p < 0.05 ) . Regression analysis revealed that cited affiliation with an epidemiology department and cited funding were associated with higher quality scores . Failure to conceal r and omization , to blind outcome assessors , and to describe why patients were excluded result ed in significantly lower quality scores ( p < 0.05 ) , more than the 5 % decrease expected by removal of each item . A priori calculations of sample size were rarely performed in the review ed studies , and only 2 % of the studies with negative results included a post hoc power analysis . The Detsky quality scale met accepted st and ards of interobserver reliability ( kappa , 0.87 ; 95 % confidence interval , 0.70 to 0.95 ) . Conclusions : Few studies published in The Journal of Bone and Joint Surgery were r and omized trials . More than half of the trials were limited by a lack of concealed r and omization , lack of blinding of outcome assessors , or failure to report reasons for excluding patients . Application of st and ardized guidelines for the reporting of clinical trials in orthopaedics should improve quality BACKGROUND AND PURPOSE Systematic review s and meta-analyses often include an evaluation of the method ological quality of the individual studies that have been included , and are usually conducted by at least 2 individuals . The objective of this study was to assess the method ological quality and reliability of a series of r and omized controlled trials ( RCTs ) of both pharmacological and nonpharmacological interventions by use of the 10-item Physiotherapy Evidence -Based Data base ( PEDro ) Scale . METHODS Two abstract ors independently review ed 81 RCTs assessing a variety of interventions . The Cohen kappa statistic and the intraclass correlation coefficient ( ICC ) were used to assess agreement between abstract ors . RESULTS The average total PEDro scores were 5.94 ( SD=1.43 ) for all studies combined , 6.88 ( SD=1.2 ) for pharmacological studies , and 5.29 ( SD=1.26 ) for nonpharmacological studies . The median score for pharmacological studies was significantly higher than that for nonpharmacological studies ( 7 versus 5 ) . Pair-wise kappa scores ranged from a low of .452 for concealed allocation among drug trials to perfect agreement ( 1.00 ) for r and omization and reporting of results from between-group comparisons . The ICCs associated with the cumulative PEDro score were .91 ( 95 % confidence interval [CI]=.83-.94 ) for all studies , .89 ( 95 % CI=.78-.95 ) for pharmacological studies , and .91 ( 95 % CI=.84-.952 ) for nonpharmacological studies . DISCUSSION AND CONCLUSION The method ological quality for pharmacological interventions was significantly higher than that for nonpharmacological interventions . There was good agreement between raters at an individual item level and in total PEDro scores . A lack of reporting clarity , poor organization of the report , or the failure to include salient details contributed to less-than-perfect agreement between raters OBJECTIVE To evaluate the method ologic quality of and identify method ologic issues in superiority trials assessing structural outcomes in rheumatic diseases . METHODS We search ed Medline and the Cochrane Central Register of Controlled Trials for reports of r and omized controlled trials assessing structural outcomes in osteoarthritis ( OA ) , rheumatoid arthritis ( RA ) , and osteoporosis ( OP ) published between January 1994 and December 2003 in high-impact factor general medical and specialty journals . One reader extracted data ( quality assessment , intent-to-treat analysis [ ITT analysis ] , rate of missing data , and methods of h and ling missing data ) , using a st and ardized form . RESULTS A total of 81 reports were included in the analysis ( 37 on OP , 34 on RA , and 10 on OA ) . The mean + /- SD method ologic quality scores on the Jadad scale ( possible range 0 - 5 ) and the Delphi list ( possible range 0 - 9 ) were 2.9 + /- 1.2 and 6.4 + /- 1.3 , respectively . Although it was reported in 54 articles ( 66.7 % ) that the analysis was done on an ITT basis , full ITT analysis was performed in only 6 of the studies ( 7.4 % ) , modified ITT analysis in 11 ( 13.6 % ) , and case-complete analysis in 48 ( 59.3 % ) ; the analysis was unclear in 16 articles ( 19.8 % ) . The rate of missing data on structural outcomes could be determined in only 63 articles ( 77.8 % ) and was > 20 % in approximately one-third of these reports . Methods for h and ling missing data on structural outcomes were described in 19 articles ( 23.5 % ) and were , in general , inappropriate . CONCLUSION Lack of ITT analysis and a high rate of missing data in superiority trials assessing structural outcomes may bias results from such trials . Our recommendations for improving these shortcomings may help research Output:	The majority of scales had not been rigorously developed or tested for validity and reliability . The Jadad Scale presented the best validity and reliability evidence ; however , its validity for physical therapy trials has not been supported .
MS22544	*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 accordance with a previous study of adjuvant effects of the anticonvulsant carbamazepine ( CBZ ) on the neuroleptic treatment of schizophrenic psychoses , the effects of valproate ( VPA ) were tested in a r and omly assigned double-blind , placebo-controlled study . Apart from a ( statistically nonsignificant ) psychopathological deterioration following discontinuation of VPA while on continuous neuroleptic mediation after four weeks and a statistically significant effect on " hostile belligerence " , no overall therapeutic effects of the combination of haloperidol ( HPD ) with VPA were observed under controlled conditions . Unlike the results with CBZ , concomitant use of VPA led to an even higher consumption of haloperidol and biperiden and to a higher rate of extrapyramidal symptoms compared with the corresponding placebo group , although these differences did not attain statistical significance . In regard to use of the sedative neuroleptic chlorprothixene , there was a trend toward lower doses in the VPA group than in the placebo group . From these results , adjuvant effects like those of carbamazepine in the neuroleptic treatment of schizophrenic psychoses could not be confirmed for valproate in the present study . However , the trend toward lower doses of sedative medication and observed effects on " hostile belligerence " may indicate sedative and /or antimanic properties of valproate which have recently been demonstrated in several controlled studies OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate Despite the plethora of clinical drug trials in tardive dyskinesia , few consistent findings have emerged . One possible reason for this is that there have been no serious attempts to define the role of major neurotransmitter systems ( dopamine , norepinephrine , acetylcholine , serotonin , GABA ) in one specific population of tardive dyskinesia patients . This study reports a series of five controlled drug trials in a population of patients with persistent tardive dyskinesia ; each drug probed one of four neurotransmitter systems . The intra- and interpatient responses are analyzed and the implication s of the pharmacologic response profiles for the clinical management of tardive dyskinesia are discussed As a treatment for tardive dyskinesia , sodium valproate was tested in a double-blind placebo-controlled parallel group trial , with 6-week base-line observation period followed by 6 weeks of treatment . Sodium valproate was not found to be an effective treatment for either tardive dyskinesia or drug-induced Parkinsonism , and did not affect mental state or behaviour The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas The hypothesis of a gamma-aminobutyric acid ( GABA ) involvement in the pathophysiology of schizophrenia has been recently proposed but not confirmed . As GABA has been shown to affect basal growth hormone ( GH ) secretion in humans , the assessment of plasma GH response to a GABAergic drug , such as sodium valproate ( SV ) , in schizophrenic subjects might be a tool with which to investigate central GABA activity in this illness . For this purpose , we administered orally 800 mg of SV or placebo to 13 chronic schizophrenics and to 10 normal controls , and measured plasma GH levels before and after the drug administration . SV enhanced basal GH secretion in healthy male volunteers , but not in chronic schizophrenics . These results suggest a defect of the endogenous GABA system in chronic schizophrenia . Whether the reduced responsiveness observed represents a primary defect or a secondary alteration of the GABA system in schizophrenia is as yet unknown This double-blind , r and omized , multicenter study investigated the use of divalproex with an antipsychotic agent in patients hospitalized for acute exacerbation of schizophrenia . Patients ( n=249 ) who met DSM-IV criteria for schizophrenia were r and omly assigned to receive olanzapine monotherapy , risperidone monotherapy , divalproex plus olanzapine , or divalproex plus risperidone for 28 days . Divalproex was initiated at 15 mg/kg/day and titrated over 12 days to a maximum dosage of 30 mg/kg/day . Olanzapine and risperidone , were , respectively , initiated at 5 and 2 mg/day and were titrated over the first 6 days to respective target fixed daily dosages of 15 and 6 mg/day . Improvements from baseline were observed at all evaluation points throughout the 28-day treatment period in the two combination therapy and the two antipsychotic monotherapy groups , with statistically significant treatment differences favoring combination therapy as soon as day 3 for Positive and Negative Syndrome Scale ( PANSS ) total score , derived Brief Psychiatric Rating Scale ( BPRSd ) total score , as well as PANSS and BPRSd subscales . These findings were confirmed in post hoc repeated- measures analyses of variance in which treatment differences favoring combination therapy were observed for PANSS total ( p=0.020 ) and PANSS positive scale scores ( p=0.002 ) . Both combination therapy and antipsychotic monotherapy were well tolerated . Treatment with divalproex in combination with an atypical antipsychotic agent result ed in earlier improvements in a range of psychotic symptoms among acutely hospitalized patients with schizophrenia . Further evaluation is warranted to confirm these findings Experimental and clinical data suggest that GABA-ergic drugs such as valproate may have a potential role in the treatment of schizophrenia . The authors design ed a 21-day prospect i ve , double-blind , r and omized , placebo-controlled pilot study of divalproex sodium as add-on treatment to haloperidol in 12 hospitalized patients with acute exacerbations of chronic schizophrenia . All patients received haloperidol 10 mg/day for 3 days and 15 mg/day for the remaining 18 days . In addition , five patients were r and omly assigned to receive divalproex augmentation and seven to receive placebo . The divalproex dose was adjusted to a target serum concentration of 75 microg/mL for 2 weeks ; placebo replaced divalproex during the third and last weeks to determine any carryover effect . Psychiatric rating scales were administered at baseline and on days 7 , 14 , and 21 . Although the placebo group improved with haloperidol treatment , the divalproex group demonstrated greater improvement . On day 21 , the divalproex group had greater improvement from baseline on the Clinical Global Impression Scale ( p < or = 0.04 ) , Brief Psychiatric Rating Scale ( p < or = 0.13 ) , and Schedule for Assessment of Negative Symptoms scores ( p < or = 0.007 ) . After divalproex withdrawal on day 15 , a carryover effect was observed during week 3 . The authors concluded that the addition of divalproex sodium to st and ard antipsychotic drugs may prove effective in relieving the symptoms of acute schizophrenia . Future studies may benefit from the design of this pilot study . However , it is premature to apply this augmentation strategy in the clinical setting just yet because of the small sample size and the likely heterogeneity of the disorder OBJECTIVE This study compared the specific antihostility effects of atypical antipsychotic monotherapy ( olanzapine or risperidone ) with that of combination treatment with divalproex sodium among patients with schizophrenia experiencing an acute psychotic episode . METHODS A total of 249 in patients with schizophrenia were r and omly assigned to receive olanzapine plus placebo , olanzapine plus divalproex , risperidone plus placebo , or risperidone plus divalproex in a double-blind , 28-day multicenter trial . The target daily dose was 15 milligrams for olanzapine , 6 milligrams for risperidone , and up to 30 milligrams per kilogram ( minimum , 15 milligrams per kilogram ) for divalproex . The hostility item of the Positive and Negative Syndrome Scale ( PANSS ) was the principal outcome measure . Covariates included the PANSS items reflecting positive symptoms of schizophrenia ( delusions , suspiciousness/persecution , gr and iosity , unusual thought content , conceptual disorganization , and hallucinatory behavior ) . RESULTS Combination treatment with risperidone or olanzapine plus divalproex was associated with different scores on the hostility item of the PANSS compared with antipsychotic monotherapy . Combination therapy had a significantly greater antihostility effect at days 3 and 7 than monotherapy . This result was not seen beyond the first week of treatment , but there was a trend toward a difference in effect for the entire treatment period . The effect on hostility appears to be statistically independent of antipsychotic effect on other PANSS items reflecting delusional thinking , a formal thought disorder , or hallucinations . CONCLUSIONS Divalproex sodium may be useful as an adjunctive agent in specifically reducing hostility in the first week of treatment with risperidone or olanzapine among patients with schizophrenia experiencing an acute psychotic episode The objective of this study was to compare the effects of carbamazepine ( CBZ ) and valproate ( VPA ) cotreatment on the plasma levels of haloperidol and on the psychopathologic outcome in schizophrenic disorders . In this controlled clinical trial , 27 patients with an ICD-10 diagnosis of schizophrenia ( N = 24 ) or schizoaffective disorder ( N = 3 ) were r and omly assigned to receive 4 weeks of treatment with either haloperidol alone , haloperidol with CBZ , or haloperidol with VPA . Whereas the haloperidol dose remained stable , the antiepileptic drug doses were adjusted to achieve therapeutic plasma levels . Clinical state was rated by the Positive subscale of the Positive and Negative Syndrome Scale and the Inpatient Multidimensional Psychiatric Scale . The use of CBZ was associated with significantly lower haloperidol plasma levels and with a worse clinical outcome compared with antipsychotic monotherapy . VPA had no significant effect on either plasma levels or on psychopathology . Our results suggest that comedication with haloperidol and CBZ is associated with a high risk for treatment failure . This might be a result of a pharmacokinetic interaction on the hepatic level . The concomitant use of VPA with neuroleptic therapy is not impaired by clinical ly significant drug interactions , but it is not associated with a better outcome under our conditions The effect of sodium valproate , a drug which has been demonstrated to increase gamma-aminobutyric acid levels in the CNS , on tardive dyskinesia and psychiatric symptoms was investigated in a double-blind cross-over study on 32 chronic psychiatric patients . The oro-facial Output:	REVIEW ER 'S CONCLUSIONS Based on r and omised trial-derived evidence which is currently available , there are no data to support or to refute the use of valproate as a sole agent for schizophrenia . There is some evidence for a more rapid improvement with valproate augmentation , but this effect vanished over time .
MS22545	*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: Iloprost , a stable prostacyclin analogue , was given by intravenous infusion to 29 patients with severe Raynaud 's phenomenon , 26 of whom had systemic sclerosis ( SS ) , and compared with placebo infusion in a double blind crossover trial . Iloprost significantly lessened the number and the severity of attacks compared with placebo . Nine patients expressed a preference for effectiveness of treatment , eight of these in favour of Iloprost . Thermography failed to show any long term effect of Iloprost . Side effects of headache , flushing , nausea , and vomiting were common , and the inconvenience of intravenous administration may limit its routine use OBJECTIVE --To compare the efficacy , tolerance and safety of 50 - 150 micrograms orally administered iloprost given twice a day versus placebo in patients with Raynaud 's syndrome . METHODS --The study was multicentre ( n = 3 ) , double blind and placebo controlled . Sixty three patients who had eight or more vasospastic attacks per week were enrolled . After a one week run-in period , all patients received either iloprost or placebo treatment to a maximum tolerated dose of 150 micrograms twice a day for 10 days . Diary cards assessed the duration and severity of the vasospastic attacks . Side effects were monitored by direct question ing . A global assessment of treatment efficacy was made by the patient at the end of treatment and two weeks later . RESULTS --Patient opinion tended to favour iloprost at the end of the 10 day treatment phase ( p = 0.09 ) and this was significant at day 24 ( the follow up visit ) ( p = 0.011 ) . Although the duration and severity of attacks tended to decrease in the iloprost treated group , these results tended not to reach statistical significance ( for severity p = 0.06 at end of treatment , p = 0.09 on day 24 ) . CONCLUSION --Iloprost administered intravenously has been shown to be of benefit in the treatment of the Raynaud 's syndrome associated with systemic sclerosis , but this route of administration is inconvenient . This study evaluated the use of iloprost administered orally to patients with Raynaud 's syndrome . Patient documented improvement was significantly improved by iloprost . Diary card analysis showed a trend in favour of iloprost , but these results did not reach statistical significance R and omized controlled trials ( RCTs ) in Raynaud 's phenomenon ( RP ) have shown conflicting efficacy data . Also , there is no consensus on the outcome measures that should be used . Our objectives were to assess the reliability of individual core set measures used in 3 RCTs , evaluate the placebo response for individual core set measures , and determine if a composite of individual core set measures will decrease the placebo response , which may improve our ability to see treatment effects in future trials OBJECTIVE We conducted this study to assess the clinical usefulness and physiologic effects of intravenous iloprost in patients with Raynaud 's phenomenon secondary to systemic sclerosis . METHODS Thirty-five patients with Raynaud 's phenomenon secondary to systemic sclerosis , including 11 with digital ischemic ulcerations , were enrolled in a double blind placebo controlled parallel study in 2 centers . Following a 2 week washout , subjects received intravenous iloprost ( 0.5 - 2.0 ng/kg/min ) or saline by continuous infusion for 6 h on 5 consecutive days . Clinical assessment s , status of digital ulcers , measures of in vivo platelet activation and detailed studies of peripheral vascular response to cold challenge , were performed at entry , at 5 days of therapy and at biweekly intervals for 10 weeks . RESULTS Complete healing of all cutaneous lesions ( ulcers , fissures , and paronychia ) was observed 10 weeks after treatment in 6 of 7 patients receiving iloprost versus none of 4 receiving placebo ( p = 0.015 ) . Ischemic digital tip ulcers completely healed in all 4 patients with ulcers in the iloprost group , but none in the placebo group ( p = 0.029 ) . Patient diaries of frequency , duration and symptoms of Raynaud 's phenomenon showed improvement in both groups . Critical ischemic temperature ( finger temperature during controlled cold challenge at which Raynaud 's or loss of detectable digital blood flow occurred ) progressively decreased in the iloprost group from 21.3 + /- 7.3 degrees C at baseline to a minimum of 16.1 + /- 3.2 degrees C at 8 weeks after treatment ( p = 0.076 ) , whereas no consistent changes were observed in the placebo group . Treatment was associated with improvement in the rate of skin temperature recovery following cold challenge . No changes were noted in ambient digital skin temperature , total digital blood flow , finger systolic pressure or in measures of in vivo platelet activation . One subject dropped out with chest pain , but adverse effects of nausea , vomiting , headache and jaw pain were otherwise limited to the 5 days of drug infusion . CONCLUSION Iloprost appears useful for the treatment of digital ulcers in systemic sclerosis and is associated with evidence of prolonged physiologic improvement although the mechanism of this effect remains unclear Twelve female patients with severe secondary Raynaud 's phenomenon were treated in a r and omized order with both placebo and Iloprost infusions . Infusions were for 5 hours on 3 consecutive days and Iloprost was administered at variable dosage from 1.0 to 3.0 ng/kg/min . A 6-week follow-up period was used between the two sets of infusions . A significant number of patients reported Iloprost had improved Raynaud 's symptomatology compared with placebo and this effect lasted for up to 6 weeks . The number of attacks of Raynaud 's as recorded by patients in diary books was similarly reduced after Iloprost . Digital and nail-bed blood flows measured by laser-Doppler methods were increased for up to 6 weeks after Iloprost , but not after placebo infusions . Iloprost may be a useful therapeutic agent in the treatment of severe secondary Raynaud 's syndrome OBJECTIVE To evaluate the efficacy and tolerability of an oral preparation of iloprost , a prostacyclin analog , in patients with Raynaud 's phenomenon ( RP ) secondary to systemic sclerosis ( scleroderma ) . METHODS A multicenter , r and omized , parallel-group , placebo-controlled double-blind study was performed at university and community-based medical centers . Patients were r and omly assigned to receive either 50 microg of iloprost orally twice daily or an identical gelatin-coated capsule containing placebo for 6 weeks . Outcome measures included average total daily duration of RP attacks , average number of RP attacks , and RP condition scored via a st and ardized daily diary . RESULTS Three hundred eight patients with scleroderma ( 272 women , 36 men , mean age 49 years [ range 18 - 80 ] ) were enrolled . One hundred fifty seven were assigned to receive iloprost and 151 to receive placebo . One hundred forty-three patients in the iloprost group ( 91.1 % ) and 144 in the placebo group ( 95.4 % ) completed the 6-week treatment phase . Fifteen of these treated patients ( 8 iloprost , 7 placebo ) failed to complete all of the followup visits . The mean reduction in the average duration of attacks from baseline to week 5 - 6 was 24.32 minutes in the iloprost group and 34.34 minutes in the placebo group ( P = 0.569 ) . Likewise , the mean reduction from baseline to week 5 - 6 in the daily frequency of attacks was 1.02 in the iloprost group and 0.83 in the placebo group ( P = 0.459 ) . The Raynaud 's condition score , a patient-completed assessment of the severity of RP attacks , was reduced by 1.32 in the iloprost group and 1.00 in the placebo group ( P = 0.323 ) . The lack of significant difference between treatment groups did not change when a variety of factors , including use of other vasodilators , duration of disease , classification of scleroderma ( limited versus diffuse ) , or number of baseline digital ulcers were taken into account . Premature withdrawal from the study due to adverse events occurred in 10 patients ( 6.4 % ) in the iloprost group and 3 ( 2.0 % ) in the placebo group ( P = 0.058 ) . CONCLUSION Oral iloprost at a dosage of 50 microg twice daily is no better than placebo for management of RP secondary to scleroderma , either during 6 weeks of treatment or during 6 weeks of posttreatment followup Iloprost is a chemically stable analog of prostagl and in I2 showing the same properties as the naturally occurring substance , but with advantages of ease of h and ling and administration to patients . A double blind within patient comparison of intravenous iloprost and placebo was undertaken in 13 patients with Raynaud 's phenomenon severe enough to warrant short term hospitalization for intravenous dilator therapy ; thermography was used as one form of assessment . Our results , while showing improvements in frequency of Raynaud 's attacks after iloprost compared with placebo , show no significant effects on other variables Raynaud phenomenon occurs in more than 90 % of patients with systemic sclerosis . In these patients the digital arteries and precapillary arterioles show marked fibrosis of the intima and luminal narrowing [ 1 , 2 ] . This peripheral vascular disease has been associated with in vivo platelet activation and abnormal vascular reactivity [ 3 - 5 ] . Vasodilator therapy can prevent or ameliorate Raynaud episodes in patients with scleroderma , thus providing increased blood flow and healing of ischemic digital lesions . Unfortunately , currently available vasodilators are incompletely effective in treating Raynaud phenomenon in patients with systemic sclerosis [ 6 , 7 ] . Iloprost is a chemically stable prostacyclin analog with both vasodilating and platelet inhibitory effects [ 8 - 10 ] . Iloprost is not yet available but is being studied in clinical trials for various vascular conditions , including ischemic ulcers , pulmonary hypertension , and vasospastic disorders . Short-term intravenous infusions of prostacyclin have been beneficial in the treatment of Raynaud phenomenon [ 11 - 14 ] . Previous studies suggest that iloprost is helpful in the treatment of Raynaud phenomenon and ischemic ulcers secondary to systemic sclerosis [ 15 - 22 ] . However , these studies have been conducted on small numbers of patients and have either been uncontrolled [ 19 - 21 ] or based on a cross-over design [ 15 - 17 ] . Because the effects of iloprost may persist for 6 to 10 weeks , a parallel study design is preferable . We report the first double-blind , placebo-controlled , parallel-group , multicenter study design ed to investigate the efficacy of iloprost in treating patients with Raynaud phenomenon secondary to systemic sclerosis . Methods Patients Out patients with Raynaud phenomenon secondary to systemic sclerosis with either diffuse cutaneous or limited cutaneous variants from 12 clinical centers were eligible to enter the study . The diagnosis of Raynaud phenomenon was based on a history of episodic digital pallor and cyanosis . The diagnosis of systemic sclerosis was made according to the classification criteria developed by the American Rheumatism Association [ 23 ] . Patients were considered to have sufficiently severe Raynaud phenomenon for study entry if they met either of the following criteria : a minimum of 8 Raynaud attacks per week documented by patient diary during the 2 weeks before the first day of infusion or one or more cutaneous ischemic finger lesions ( ulcers , fissures , or paronychiae ) . The patient could be male or female and at least 18 years old . Women of childbearing age were required to practice a medically acceptable method of birth control and to have a negative pregnancy test 1 week before the start of infusion and on the morning of the first day of infusion . All the patients provided written informed consent . Patients were excluded if they met any of the following conditions : surgical sympathectomy done within the past 12 months ; bleeding diathesis or a platelet disorder ; stroke , transient cerebral ischemic attack , or myocardial infa rct ion within the past 6 months ; history of angina pectoris within the preceding 12 months ; evidence within the preceding 4 weeks of the onset of renal disease manifested by new hypertension or abnormal urinalysis results , evidence of microangiopathic hemolytic anemia , or azotemia ; hypertension not controlled by diuretics , clonidine , or angiotensin-converting-enzyme inhibitors ; evidence of cancer within the past year ; evidence of any uncontrolled cardiovascular , pulmonary , renal , hepatic , endocrine , neurologic , or gastrointestinal disease ; smoking within the preceding 4 weeks ; history of substance abuse ( drug or alcohol ) ; or participation in an investigational drug study within 4 weeks before pretreatment . The patients were required to discontinue certain medications at least 14 days before the first day of the study . Among the disallowed medications were aspirin , dipyridamole , calcium channel blockers , and other vasodilators . Treatment Regimen Iloprost was supplied in ampules containing 0.1 mg of the active drug in 1 mL of a sterile pyrogen-free solution . Placebo ampules contained the same solution without iloprost . Infusion rates of 0.5 to 2.0 ng/kg per minute were used , based on studies showing that 0.5 ng/kg per minute was the usual threshold for the inhibition of platelet aggregation and that infusion rates greater than 2 ng/kg per minute frequently produced side effects . Patients were assigned r and omly to one of two treatment groups , either a Output:	We concluded iloprost may lead to little or no difference in the frequency or severity of secondary Raynaud , and it is associated to adverse effects and important costs
MS22546	*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 estimate the effect of adding exercise classes , spinal manipulation delivered in NHS or private premises , or manipulation followed by exercise to “ best care ” in general practice for patients consulting with back pain . Fig 1 Progress of the UK BEAM trial Design Pragmatic r and omised trial with factorial design . Setting 181 general practice s in Medical Research Council General Practice Research Framework ; 63 community setting s around 14 centres across the United Kingdom . Participants 1334 patients consulting their general practice s about low back pain . Main outcome measures Scores on the Rol and Morris disability question naire at three and 12 months , adjusted for centre and baseline scores . Results All groups improved over time . Exercise improved mean disability question naire scores at three months by 1.4 ( 95 % confidence interval 0.6 to 2.1 ) more than “ best care . ” For manipulation the additional improvement was 1.6 ( 0.8 to 2.3 ) at three months and 1.0 ( 0.2 to 1.8 ) at 12 months . For manipulation followed by exercise the additional improvement was 1.9 ( 1.2 to 2.6 ) at three months and 1.3 ( 0.5 to 2.1 ) at 12 months . No significant differences in outcome occurred between manipulation in NHS premises and in private premises . No serious adverse events occurred . Conclusions Relative to “ best care ” in general practice , manipulation followed by exercise achieved a moderate benefit at three months and a small benefit at 12 months ; spinal manipulation achieved a small to moderate benefit at three months and a small benefit at 12 months ; and exercise achieved a small benefit at three months but not 12 months BACKGROUND AND OBJECTIVE To develop a checklist of items measuring the quality of reports of r and omized clinical trials ( RCTs ) assessing nonpharmacological treatments ( NPTs ) . STUDY DESIGN AND SETTING The Delphi consensus method was used to select and reduce the number of items in the checklist . A total of 154 individuals were invited to participate : epidemiologists and statisticians involved in the field of methodology of RCTs ( n = 55 ) , members of the Cochrane Collaboration ( n = 41 ) , and clinicians involved in planning NPT clinical trials ( n = 58 ) . Participants ranked on a 10-point Likert scale whether an item should be included in the checklist . RESULTS Fifty-five experts ( 36 % ) participated in the survey . They were experienced in systematic review s ( 68 % were involved in the Cochrane Collaboration ) and in planning RCTs ( 76 % ) . Three rounds of the Delphi method were conducted to achieve consensus . The final checklist contains 10 items and 5 subitems , with items related to the st and ardization of the intervention , care provider influence , and additional measures to minimize the potential bias from lack of blinding of participants , care providers , and outcome assessors . CONCLUSIONS This tool can be used to critically appraise the medical literature , design NPT studies , and assess the quality of trial reports included in systematic review Abstract . The literature on the efficacy of traction in the treatment of low back pain ( LBP ) is conflicting . The aim of this study was to examine its efficacy in this disorder . Forty-two patients with at least 6 weeks of nonspecific LBP were selected . Demographic data were obtained . All patients completed the Oswestry disability index ( ODI ) to assess disability and the 10-cm visual analog scale ( VAS ) for evaluation of pain . Subjects were r and omly assigned into group 1 , receiving only st and ard physical therapy , or group 2 , receiving st and ard physical therapy with conventional lumbar traction . St and ard physical therapy consisted of local heat , ultrasound for the lumbar region , and an active exercise program , given for ten sessions in all . The subjects received instruction on correct posture and recommended therapeutic exercises . They were reevaluated at the end of treatment and at 3-month follow-up . The mean outcome measures were global improvement and satisfaction with the therapy , as well as disability by ODI and pain by VAS . There were no group differences in terms of demographic and baseline clinical characteristics . There was a significant reduction in pain intensity and disability at the end of treatment in both groups . There was complete or mild improvement in 47.6 % of group 1 and 40 % of group 2 . The satisfaction rate with both treatments was more than 70 % immediately after the therapies . During the 3-month period , the outcome measures except disability remained statistically stable , with no difference amongst groups . Disability was significantly reduced at follow-up in both groups . Of the patients , 51 % continued with the recommended exercises and had significantly lower disability scores than those who did not continue with the exercises . Pain and global improvement were also better in this group , but the difference was not statistically significant . In conclusion , no specific effect of traction on st and ard physical therapy was observed in our study group . We suggest focusing on back education and exercise therapy in the management of patients suffering from this chronic condition Our aim is to investigate the effects of three therapeutic approaches in the chronic low back pain on pain , spinal mobility , disability , psychological state , and aerobic capacity . Sixty patients with chronic low back pain were r and omized to three groups : group 1 , aerobic exercise + home exercise ; group 2 , physical therapy ( hot pack , ultrasound , TENS ) + home exercise ; group 3 , home exercise only . Spinal mobility , pain severity , disability , and psychological disturbance of the patients were assessed before and after the treatment and at 1-month follow-up . Aerobic capacities of the patients were measured before and after treatment . All of the groups showed similar decrease in pain after the treatment and at 1-month follow-up , and there was no significant difference between the groups . In group 2 , a significant decrease in Beck Depression Inventory scores was observed with treatment . At 1-month follow-up , group 1 and 2 showed significant decreases in General Health Assessment Question naire scores . In group 2 , there was also a significant improvement in Rol and Morris Disability scores . There were similar improvements in exercise test duration and the MET levels in all the three groups . All of the three therapeutic approaches were found to be effective in diminishing pain and thus increasing aerobic capacity in patients with chronic low back pain . On the other h and , physical therapy + home exercise was found to be more effective regarding disability and psychological disturbance The efficacy of ultrasound therapy in the management of back pain result ing from rupture of the intervertebral disc was evaluated in 3 groups : treatment , placebo , and control . Range of motion of total flexion and extension , total side flexion and total rotation of the lumbar spine , and subjective assessment of pain were used as criteria to determine the efficacy of treatment . Group comparisons showed statistical significance in favor of the treatment group ( p 0.01 ) , leading to the conclusion that ultrasound therapy is significantly effective in the treatment of back pain result ing from prolapse of the lumbar intervertebral disc Study Design . A r and omized controlled trial . Objective . To investigate the effectiveness and cost of usual care plus patient choice of acupuncture , chiropractic , or massage therapy ( choice ) compared with usual care alone in patients with acute low back pain ( LBP ) . Summary of Background Data . Few studies have evaluated care models with facilitated access to and financial coverage for adjunctive complementary and alternative medicine therapies . Methods . A total of 444 patients with acute LBP ( < 21 days ) were recruited from 4 clinical sites and r and omized into 2 groups : usual care or choice . Outcomes included symptoms ( bothersomeness ) , functional status ( Rol and ) , and satisfaction between baseline and 5 weeks , and cost of medical care in the 12 weeks after r and omization . Results . After 5 weeks , providing patients with a choice did not yield clinical ly important reductions in symptoms ( median −4 , [ interquartile range −7 , −2 ] for usual care , and −5 [ −7 , −3 ] for choice ; P = 0.002 ) or improvements in functional status ( −8 [ −13 , −2 ] for usual care , and −9 [ −15 , −4 ] for choice ; P = 0.15 ) . Although there was a significantly greater satisfaction with care in the choice group , this came at a net increase in costs of $ 244 per patient . This consisted of a $ 99 reduction in the average cost to the insurer for medical care but an additional cost of $ 343 , for an average of 6.0 complementary and alternative medicine treatments per patient . Conclusions . A model of care that offered access to a choice of complementary and alternative medicine therapies for acute LBP did not result in clinical ly significant improvements in symptom relief or functional restoration . This model was associated with greater patient satisfaction but increased total costs . Future evaluations of this choice model should focus on patients with chronic conditions ( including chronic back pain ) for which conventional medical care is often costly and of limited benefit Background The causes of chronic low back pain ( CLBP ) remain obscure and effective treatment of symptoms remains elusive . A mechanism of relieving chronic pain based on the consequences of conflicting unpleasant sensory inputs to the central nervous system has been hypothesised . As a result a device was generated to deliver sensory discrimination training ( FairMed ) , and this r and omised controlled trial compared therapeutic effects with a comparable treatment modality , TENS . Methods 60 patients with CLBP were recruited from physiotherapy referrals to a single-blinded , r and omised controlled , non-inferiority trial . They were r and omised to receive either FairMed or TENS and asked to use the allocated device for 30 minutes , twice a day , for 3 weeks . The primary outcome variable measured at 0 and 3 weeks was pain intensity measured using a visual analogue scale averaged over 7 days . Secondary outcome measures were Oswestry Disability Index , 3 timed physical tests , 4 question naires assessing different aspects of emotional coping and a global measure of patient rating of change . Data were analysed for the difference in change of scores between groups using one-way ANOVA . Results Baseline characteristics of the two groups were comparable . The primary outcome , change in pain intensity ( VAS ) at 3 weeks showed a mean difference between groups of -0.1 , ( non significant p = 0.82 ) . The mean difference in change in ODI scores was 0.4 ; ( non significant p = 0.85 ) . Differences in change of physical functioning showed that no significant difference in change of scores for any of these test ( p = 0.58 – 0.90 ) . Changes in scores of aspects of emotional coping also demonstrated no significant difference in change scores between the groups ( p = 0.14 – 0.94 ) . Conclusion FairMed was not inferior to TENS treatment . The findings have implication s for further research on current chronic pain theories and treatments . Further work to explore these mechanisms is important to exp and our underst and ing of chronic pain and the role of neuro-modulation . Trial Registration UKCRN Study ID OBJECTIVE This study measures and compares the outcome of traction , ultrasound , and low-power laser ( LPL ) therapies by using magnetic resonance imaging and clinical parameters in patients presenting with acute leg pain and low back pain caused by lumbar disc herniation ( LDH ) . METHODS A total of 60 patients were enrolled in this study and r and omly assigned into 1 of 3 groups equally according to the therapies applied , either with traction , ultrasound , or LPL . Treatment consisted of 15 sessions over a period of 3 weeks . Magnetic resonance imaging examinations were done before and immediately after the treatment . Physical examination of the lumbar spine , severity of pain , functional disability by Rol and Disability Question naire , and Modified Oswestry Disability Question naire were assessed at baseline , immediately after , and at 1 and 3 months after treatment . RESULTS There were significant reductions in pain and disability scores between baseline and follow-up periods , but there was not a significant difference between the 3 treatment groups at any of the 4 interview times . There were significant reductions of size of the herniated mass on magnetic resonance imaging after treatment , but no differences between groups . CONCLUSIONS This study showed that traction , ultrasound , and LPL therapies were all effective in the treatment of this group of patients with acute LDH . These results suggest that conservative measures such as traction , laser , and ultrasound treatments might have an important role in the treatment of acute LDH Study Design . A r and omized controlled trial was conducted . Objective . To determine the efficacy of osteopathic manipulative treatment as a complementary treatment for chronic nonspecific low back pain . Summary of Background Data . Osteopathic manipulative treatment may be useful for acute or subacute low back pain . However , its role in chronic low back pain is unclear . Methods . This trial was conducted in a university-based clinic from 2000 through 2001 . Of the 199 subjects who responded to recruitment procedures , 91 met the eligibility criteria . They were r and omized , with 82 patients completing the 1-month follow-up evaluation , 71 completing the 3-month evaluation , and 66 completing the 6-month evaluation . The subjects were r and omized to osteopathic manipulative treatment , sham manipulation , or a no-intervention control group , and they were allowed to continue their usual care for low back pain . The main outcomes included the SF-36 Health Survey , a 10-cm visual analog scale for overall back pain , the Rol and –Morris Disability Question naire , lost work or school days because of back pain , and satisfaction with back care . Results . As compared with the no-intervention control subjects , the patients who received osteopathic manipulative treatment reported greater improvements in back pain , greater satisfaction with back care throughout the trial , better physical functioning and mental health at 1 month , and fewer cotreatments at 6 months . The subjects who received sham manipulation also reported greater improvements in back pain and physical functioning and greater satisfaction than the no-intervention control subjects . There were no significant benefits with osteopathic manipulative treatment , as compared with sham manipulation . Conclusions . Osteop Output:	For acute patients with LBP and leg pain attributed to disc herniation , ultrasound , traction , and low-power laser obtained similar results . For chronic LBP patients without leg pain , ultrasound was less effective than spinal manipulation , whereas a shock wave device and transcutaneous electrical nerve stimulation led to similar results . The available evidence does not support the effectiveness of ultrasound or shock wave for treating LBP .
MS22547	*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 Shock-absorbing and biomechanic shoe orthoses are frequently used in the prevention and treatment of back and lower extremity problems . One review concludes that the former is clinical ly effective in relation to prevention , whereas the latter has been tested in only 1 r and omized clinical trial , concluding that stress fractures could be prevented . OBJECTIVES To investigate if biomechanic shoe orthoses can prevent problems in the back and lower extremities and if reducing the number of days off-duty because of back or lower extremity problems is possible . DESIGN Prospect i ve , r and omized , controlled intervention trial . STUDY SUBJECTS One female and 145 male military conscripts ( aged 18 to 24 years ) , representing 25 % of all new conscripts in a Danish regiment . METHOD Health data were collected by question naires at initiation of the study and 3 months later . Custom-made biomechanic shoe orthoses to be worn in military boots were provided to all in the study group during the 3-month intervention period . No intervention was provided for the control group . Differences between the 2 groups were tested with the chi-square test , and statistical significance was accepted at P < .05 . Risk ratio ( RR ) , risk difference ( ARR ) , numbers needed to prevent ( NNP ) , and cost per successfully prevented case were calculated . OUTCOME VARIABLES Outcome variables included self-reported back and /or lower extremity problems ; specific problems in the back or knees or shin splints , Achilles tendonitis , sprained ankle , or other problems in the lower extremity ; number of subjects with at least 1 day off-duty because of back or lower extremity problems and total number of days off-duty within the first 3 months of military service because of back or lower extremity problems . RESULTS Results were significantly better in an actual-use analysis in the intervention group for total number of subjects with back or lower extremity problems ( RR 0.7 , ARR 19 % , NNP 5 , cost 98 US dollars ) ; number of subjects with shin splints ( RR 0.2 , ARR 19 % , NNP 5 , cost 101 US dollars ) ; number of off-duty days because of back or lower extremity problems ( RR 0.6 , ARR < 1 % , NNP 200 , cost 3750 US dollars ) . In an intention-to-treat analysis , a significant difference was found for only number of subjects with shin splints ( RR 0.3 , ARR 18 % , NNP 6 cost 105 US dollars ) , whereas a worst-case analysis revealed no significant differences between the study groups . CONCLUSIONS This study shows that it may be possible to prevent certain musculoskeletal problems in the back or lower extremities among military conscripts by using custom-made biomechanic shoe orthoses . However , because care-seeking for lower extremity problems is rare , using this method of prevention in military conscripts would be too costly . We also noted that the choice of statistical approach determined the outcome Orthotic insoles are suggested to prevent low back pain . This r and omized controlled study assessed if customised orthotic insoles prevent low back pain . Healthy military conscripts ( n = 228 ; mean age 19 years , range 18–29 ) were r and omly assigned to use either customised orthotic insoles ( treatment group , n = 73 ) or nothing ( control group , n = 147 ) . The main outcome measure was low back pain requiring a physician visit and result ing in minimum 1 day suspension from military duty . Twenty-four ( 33 % ) treated subjects and 42 ( 27 % ) control subjects were suspended from duty due to low back pain ( p = 0.37 ; risk difference 4.3 % ; 95 % CI : −8.7 to 17.3 % ) . Mean suspension duration was 2 days ( range 1–7 ) in both groups . Four ( 5 % ) treated subjects and eight ( 5 % ) control subjects were released from duty due to persistent low back pain ( p = 0.92 ; risk difference 0 % ; 95 % CI : −6 to 6 % ) . Use of orthotic insoles is therefore not recommended to prevent physical stress-related low back pain Study design : r and omized , double-blinded , clinical trial . Background : Low back pain is one of the commonest disorders affecting the back . The literature reflects how over time excessive pronation of the foot has become to be recognized as linked to chronic low back pain , and how the problem can evolve for the better with the use of compensating foot orthoses . Objectives : The main objective of this study is to answer the question of whether the use of a certain type of custom-made foot orthosis alleviates low back pain . Material and methods : In a sample of 51 participants with excessive subtalar pronation and chronic low back pain ( 43 women and 8 men ) , the effect of custom-made foot orthoses in low back pain was studied . The study design was a r and omized , double-blinded , clinical trial with two groups : experimental , treated with the custom-made foot orthoses , and control , treated with a placebo . Low back pain was evaluated by a visual analog scale for pain and Oswestry ’s Disability Index Question naire for lower back pain at two moments — on the day of inclusion in the study and after 4 weeks of treatment . Results : The evolution of the low back pain showed significant differences in the experimental group , showing a significant reduction of pain and disability ( p < 0.001 , visual analog scale ; p < 0.001 , Oswestry ’s Index ) . Conclusions : In the sample studied , the use of custom-made foot orthoses to control foot pronation had a short-term effect in reduction of perceived low back pain . Clinical relevance If subtalar joint hyperpronation plays a fundamental role in the pathomechanics of lower limb , and this can facilitate the development of low back pain , then controlling the abnormal mobility of subtalar joint by means of foot orthoses should improve this symptom . This article could help solve this controversy 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 Study Design . R and omized controlled trial . Objectives . To determine if the use of custom shoe orthoses can lessen the incidence of weight bearing-induced back pain . Summary of Background Data . The scientific basis for the use of orthoses to prevent back pain is based principally on studies that show that shoe orthoses can attenuate the shock wave generated at heel strike . The repetitive impulsive loading that occurs because of this shock wave can cause wear of the mechanical structures of the back . Previous r and omized studies showed mixed results in preventing back pain , were not blinded , and used orthoses for only short periods of time . Methods . A total of 404 eligible new infantry recruits without a history of prior back pain were r and omly assigned to received either custom soft , semirigid biomechanical , or simple shoe inserts without supportive or shock absorbing qualities . Recruits were review ed biweekly by an orthopaedist for back signs and symptoms during the course of 14 weeks of basic training Results . The overall incidence of back pain was 14 % . By intention-to treat and per- protocol analyses , there was no statistically significant difference between the incidence of either subjective or objective back pain among the 3 treatment groups . Significantly more recruits who received soft custom orthoses finished training in their assigned orthoses ( 67.5 % ) than those who received semirigid biomechanical orthoses ( 45.5 % ) or simple shoe inserts ( 48.6 % ) , P = 0.001 . Conclusions . The results of this study do not support the use of orthoses , either custom soft or semirigid biomechanical , as prophylactic treatment for weight bearing-induced back pain . Custom soft orthoses had a higher utilization rate than the semirigid biomechanical or simple shoe inserts . The pretraining physical fitness and sports participation of recruits were not related to the incidence of weight bearing-induced back pain Objective To compare the clinical efficacy of foot orthoses in the management of patellofemoral pain syndrome with flat inserts or physiotherapy , and to investigate the effectiveness of foot orthoses plus physiotherapy . Design Prospect i ve , single blind , r and omised clinical trial . Setting Single centre trial within a community setting in Brisbane , Australia . Participants 179 participants ( 100 women ) aged 18 to 40 years , with a clinical diagnosis of patellofemoral pain syndrome of greater than six weeks ’ duration , who had no previous treatment with foot orthoses or physiotherapy in the preceding 12 months . Interventions Six weeks of physiotherapist intervention with off the shelf foot orthoses , flat inserts , multimodal physiotherapy ( patellofemoral joint mobilisation , patellar taping , quadriceps muscle retraining , and education ) , or foot orthoses plus physiotherapy . Main outcome measures Global improvement , severity of usual and worst pain over the preceding week , anterior knee pain scale , and functional index question naire measured at 6 , 12 , and 52 weeks . Results Foot orthoses produced improvement beyond that of flat inserts in the short term , notably at six weeks ( relative risk reduction 0.66 , 99 % confidence interval 0.05 to 1.17 ; NNT 4 ( 99 % confidence interval 2 to 51 ) . No significant differences were found between foot orthoses and physiotherapy , or between physiotherapy and physiotherapy plus orthoses . All groups showed clinical ly meaningful improvements in primary outcomes over 52 weeks . Conclusion While foot orthoses are superior to flat inserts according to participants ’ overall perception , they are similar to physiotherapy and do not improve outcomes when added to physiotherapy in the short term management of patellofemoral pain . Given the long term improvement observed in all treatment groups , general practitioners may seek to hasten recovery by prescribing prefabricated orthoses . Trial registration Australian Clinical Trials Registry ACTRN012605000463673 and Clinical Trials.gov NCT00118521 OBJECTIVES The purpose of this pilot study was to investigate the feasibility of a r and omized clinical trial of shoe orthotics for chronic low back pain . METHODS The study recruited 50 patients with chronic low back pain through media advertising in a midwestern suburban area . Medical history and a low back examination were completed at a chiropractic clinic . Subjects were r and omized to either a treatment group receiving custom-made shoe orthotics or a wait-list control group . After 6 weeks , the wait-list control group also received custom-made orthotics . This study measured change in perceived pain levels ( Visual Analog Scale ) and functional health status ( Oswestry Disability Index ) in patients with chronic low back pain at the end of 6 weeks of orthotic treatment compared with no treatment and at the end of 12 weeks of orthotic treatment . RESULTS This study showed changes in back pain and disability with the use of shoe orthotics for 6 weeks compared with a wait-list control group . It appears that improvement was maintained through the 12-week visit , but the subjects did not continue to improve during this time . CONCLUSIONS This pilot study showed that the measurement of shoe orthotics to reduce low back pain and discomfort after 6 weeks of use is feasible . A larger clinical trial is needed to verify these results Soccer referees participating in large soccer tournaments may develop overuse injuries . In this study the effect of shock absorbing heel inserts in the incidence of soreness was investigated . Forty-eight referees were r and omly selected to wear shock absorbing heel inserts ( SAH ) in the 5 day-tournament , while 43 referees were the control group . A daily question naire inquiring about complaints from the locomotive system was completed for each referee and in case of any soreness they were examined by doctors to document and classify the anatomical site . Calf , thigh , back , achilles tendon and knee were the most common localizations of overuse symptoms . The incidence of soreness in achilles tendon , calf and back were significantly reduced by the use of ( SAH ) inserts 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 Output:	Conclusions There is insufficient evidence to support the use of insoles or foot orthoses as either a treatment for LBP or in the prevention of LBP . Future research should concentrate on identification of LBP patients most suited to foot orthoses or insole treatment , as there is some evidence that trials structured along these lines have a greater effect on reducing LBP
MS22548	*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 conduct a pilot study of the effect of intercessory prayer on patients entering treatment for alcohol abuse or dependence . DESIGN In addition to st and ard treatment , 40 patients admitted to a public substance abuse treatment facility for treatment of alcohol problems who consented to participate were r and omized to receive or not receive intercessory prayer ( double-blind ) by outside volunteers . Assessment s were conducted at baseline , 3 months , and 6 months . RESULTS No differences were found between prayer intervention and nonintervention groups on alcohol consumption . Compared with a normative group of patients treated at the same facility participants in the prayer study experienced a delay in drinking reduction . Those who reported at baseline that a family member or friend was already praying for them were found to be drinking significantly more at 6 months than were those who reported being unaware of anyone praying for them . Greater frequency of prayer by the participants themselves was associated with less drinking , but only at months 2 and 3 . CONCLUSION Intercessory prayer did not demonstrate clinical benefit in the treatment of alcohol abuse and dependence under these study conditions . Prayer may be a complex phenomenon with many interacting variables National evaluations of drug treatment outcomes and processes over the past 30 years have been an important source of ‘ ‘ real-world ’ ’ evidence for the effectiveness of treatment in the U.S. While they are more limited than experimental protocol s in their capacity to establish scientific causality , they excel in documenting naturally occurring patterns of treatment delivery and patient recovery . The Drug Abuse Treatment Outcome Studies ( DATOS ) is the third national evaluation of community-based treatment effectiveness funded by the National Institute on Drug Abuse ( Flynn , Craddock , Hubbard , And erson , & Etheridge , 1997 ) following the Drug Abuse Reporting Program from the 1970s ( see Simpson & Sells , 1982 , 1990 ) and the Treatment Outcomes Prospect i ve Study from the 1980s ( see Hubbard , Marsden , Rachal , Harwood , Cavanaugh , & Ginzburg , 1989 ) . The National Treatment Outcome Research Study ( NTORS ) has followed the same general model to provide the first large-scale evaluation of its kind in the United Kingdom ( Gossop , Marsden , Stewart , & Kidd , 2003 ) . Sets of papers focused on 1-year outcomes and treatment process from DATOS and NTORS have been published in special issues of Psychology of Addictive Behaviors ( Simpson & Curry , 1997 ) and Drug and Alcohol Dependence ( Simpson & Brown , 1999 ) , and evaluations of treatment for adolescents in DATOS were reported in a special issue of the Journal of Adolescent Research ( Grella & Hser , 2001 ) . Overviews of 1-year and 5-year treatment outcomes for adult cocaine users were also reported in Archives of General Psychiatry ( Simpson , Joe , Fletcher , Hubbard , & Anglin , 1999 ; Simpson , Joe , & Broome , 2002 ) , along with 1-year treatment outcomes for adolescents ( Hser et al. , 2001 ) . Bullet reports and charts that summarize findings of 75 publications from DATOS are available on its website at www.datos.org . Outcome evaluations reported in this issue and previously were conducted by the four collaborating research Objective : The primary aim of this prospect i ve study was to examine the role of several aspects of spirituality in maintaining abstinence from alcohol for one year in persons treated for alcohol dependence . The roles of alcohol abstinence self-efficacy and Alcoholics Anonymous affiliation were also examined . Method : Seventy-four adults with alcohol dependence who had completed a three-week outpatient addiction program participated in this study . Instruments used included the Spiritual Well-Being Scale , Duke Religion Index , Brief Religious Coping Scale , Alcohol Abstinence Self-Efficacy Scale , and Alcoholics Anonymous Affiliation Scale . Abstinence data was collected from participants and collaterals three , six , and twelve months after treatment discharge . Demographics , discharge measures , and the change in scores from admission to discharge were compared between those with and without 12-month alcohol abstinence using logistic regression or Fisher 's exact tests . Results : Twenty-eight participants were categorized as continuously abstinent for one year . The strongest associations between 12 month abstinence and the variables of interest were discharge scores of abstinence self-efficacy and existential well-being , and increases during treatment in scores of private spiritual practice s. Increased age demonstrated a significant association with positive outcome . Conclusion : The associations of private spiritual practice s , existential well-being , and abstinence self-efficacy with one year of continuous abstinence following treatment discharge suggest the importance of addressing issues related to these variables during alcoholism treatment . More research is needed to underst and the role of these variables in promoting and maintaining abstinence and to determine whether or not a related intervention would improve abstinence rates Abstract The purpose of the present study was to obtain preliminary data on the effectiveness of a faith-based treatment adjunct for cocaine-using homeless mothers in residential treatment . The Bridges intervention utilizes various Black church communities to provide culturally-relevant group activities and individual mentoring from volunteers . Eighteen women who were recent treatment admissions were r and omly assigned to receive St and ard Treatment plus Bridges or St and ard Treatment with an Attention Control . Participants were assessed at intake and three and six months after intake . Bridges treatment result ed in significantly better treatment retention ( 75 % vs. 20 % at six months ) than st and ard residential treatment alone . In addition , Bridges produced superior outcomes at the six month followup assessment on a secondary measure of cocaine abstinence . Creating a community of social support through Black churches appears feasible and promising , and may be a cost-effective means of providing longer-term post-treatment support for cocaine-addicted women Output:	The most common treatment outcome was abstinence followed by treatment retention , alcohol or drug use severity , and discharge status . For most studies , we found evidence suggesting at least some support for a beneficial relationship between spirituality or religion and recovery from substance use disorders .
MS22549	*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 Observational studies suggested that luteinizing hormone-releasing hormone agonists ( LHRHa ) might prevent premature ovarian failure result ing from adjuvant chemotherapy in premenopausal patients . We aim ed to test the efficacy of ovarian function preservation with the LHRHa goserelin in patients with breast cancer . PATIENTS AND METHODS In a prospect i ve , r and omized , open-label , controlled multicenter study , 60 patients younger than age 46 years with hormone-insensitive breast cancer were allocated to receive anthracycline/cyclophosphamide ( with or without taxane ) -based neoadjuvant chemotherapy with or without goserelin . The first goserelin injection was administered at least 2 weeks before the first chemotherapy cycle , continuing at 3.6 mg subcutaneously every 4 weeks until the end of the last cycle . The primary objective was the reappearance of normal ovarian function , defined as two consecutive menstrual periods within 21 to 35 days at 6 months after end of chemotherapy . RESULTS Fifty-three patients ( 88.3 % ) experienced temporary amenorrhea ( 93.3 % with v 83.3 % without goserelin ) . No significant difference was observed regarding the reappearance of menstruation at 6 months after chemotherapy ( 70.0 % with v 56.7 % without goserelin ; difference of 13.3 % ; 95 % CI , -10.85 to 37.45 ; P = .284 ) . All but one evaluable patient reported regular menses at 2 years after chemotherapy . Time to restoration of menstruation was 6.8 months ( 95 % CI , 5.2 to 8.4 ) with goserelin and 6.1 months ( 95 % CI , 5.3 to 6.8 ) without goserelin ( P = .304 ) . Chemotherapy result ed in a decreased ovarian reserve measured by inhibin B and anti-Müllerian hormone during follow-up , supporting the other findings . CONCLUSION Premenopausal patients with breast cancer receiving goserelin simultaneously with modern neoadjuvant chemotherapy did not experience statistically significantly less amenorrhea 6 months after end of chemotherapy compared with those receiving chemotherapy alone Background Chemotherapy-induced premature ovarian insufficiency ( POI ) impacts fertility and other aspects of women 's health . The OPTION trial tested whether administration of a gonadotropin-releasing hormone agonist during chemotherapy for early breast cancer reduced the risk of POI . Patients and methods This was a prospect i ve , r and omized , parallel group study of the gonadotropin-releasing hormone agonist goserelin administered before and during chemotherapy for breast cancer with stage I-IIIB disease . The primary outcome was amenorrhoea between 12 and 24 months after r and omization , supported by elevated follicle stimulating hormone concentrations to give an additional analysis as rate of POI . Results A total of 227 patients were r and omized and the primary analysis was conducted on 202 patients . Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22 % versus 38 % in the control group ( P = 0.015 ) and the prevalence of POI to 18.5 % versus 34.8 % in the control group ( P = 0.048 ) . Follicle stimulating hormone concentrations were also lower in all women treated with goserelin at both 12 and 24 months ( P = 0.027 , P = 0.001 , respectively ) . The effect of goserelin was not statistically significant in women > 40 years . Assessment of the ovarian reserve using anti-Müllerian hormone showed a marked fall in both groups during treatment to median values of 5 % of pretreatment levels in the control group and 7 % in the goserelin group , which were not significantly different between groups . Conclusion This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer , with particular efficacy in women aged ≤40 years old . The degree of ovarian protection also seems limited and the clinical significance for fertility and longer term prevention of estrogen deficiency-related outcomes needs to be determined STUDY OBJECTIVE To explore the interindividual and intraindividual variation of Pictorial Blood Loss Assessment Chart ( PBAC ) registration s of subjective perception of minimal , normal , and heavy menstrual bleeding in women using their usual sanitary protection . DESIGN Retrospective study ( Canadian Task Force classification II-3 ) . SETTING University tertiary hospital . PATIENTS Women who had participated in 4 previously published prospect i ve studies using PBAC as the outcome measure . INTERVENTIONS Patients underwent hysteroscopic removal of polyps , laparoscopic occlusion of uterine vessels , or uterine artery embolization , and control subjects received no treatment . MEASUREMENTS AND MAIN RESULTS PBAC scores , hemoglobin concentration , and subjective assessment of periodic blood loss were recorded in 429 women during 1049 menstrual cycles . The median PBAC values in groups of women who assessed their bleeding as light , normal , and heavy were 45.0 , 116.0 , and 254.5 , respectively ( p < .001 ) . Sensitivity and specificity for specific PBAC cutoff points were calculated using a receiver operating characteristic curve . The maximum sensitivity for assessment of heavy periodic blood loss ( 78.5 ) was reached at a PBAC score of 160 . The corresponding specificity was 75.8 . At PBAC values below 130 , 90 % of the women reported normal blood loss , and 91 % had hemoglobin values > 12.0 g/dL. The reliability of repeated PBAC scores for individual measures was assessed via calculation of the intraclass correlation coefficient , which for repeated PBAC measurements was 0.86 ( 95 % confidence interval , 0.80 - 0.90 ) for average measures . CONCLUSION The interindividual variation was high , and the intraindividual variation was low . A low PBAC score may be used to define treatment end points for clinical use or in trials IMPORTANCE Whether the administration of luteinizing hormone-releasing hormone analogues ( LHRHa ) during chemotherapy is a reliable strategy to preserve ovarian function is controversial owing to both the lack of data on long-term ovarian function and pregnancies and the safety concerns about the potential negative interactions between endocrine therapy and chemotherapy . OBJECTIVE To evaluate long-term results of LHRHa-induced ovarian suppression during breast cancer chemotherapy . DESIGN , SETTING , AND PARTICIPANTS Parallel , r and omized , open-label , phase 3 superiority trial conducted at 16 Italian sites . Between October 2003 and January 2008 , 281 premenopausal women with stage I to III hormone receptor-positive or hormone receptor-negative breast cancer were enrolled . Last annual follow-up was June 3 , 2014 . INTERVENTIONS Patients were r and omized to receive adjuvant or neoadjuvant chemotherapy alone ( control group ) or chemotherapy plus triptorelin ( LHRHa group ) . MAIN OUTCOMES AND MEASURES The primary planned end point was incidence of chemotherapy-induced early menopause . Post hoc end points were long-term ovarian function ( evaluated by yearly assessment of menstrual activity and defined as resumed by the occurrence of at least 1 menstrual cycle ) , pregnancies , and disease-free survival ( DFS ) . RESULTS A total of 281 women ( median age , 39 [ range , 24 - 45 ] years ) were r and omized . Median follow-up was 7.3 years ( interquartile range , 6.3 - 8.2 years ) . The 5-year cumulative incidence estimate of menstrual resumption was 72.6 % ( 95 % CI , 65.7%-80.3 % ) among the 148 patients in the LHRHa group and 64.0 % ( 95 % CI , 56.2%-72.8 % ) among the 133 patients in the control group ( hazard ratio [ HR ] , 1.28 [ 95 % CI , 0.98 - 1.68 ] ; P = .07 ; age-adjusted HR , 1.48 [ 95 % CI , 1.12 - 1.95 ] ; P = .006 ) . Eight pregnancies ( 5-year cumulative incidence estimate of pregnancy , 2.1 % [ 95 % CI , 0.7%-6.3 % ] ) occurred in the LHRHa group and 3 ( 5-year cumulative incidence estimate of pregnancy , 1.6 % [ 95 % CI , 0.4%-6.2 % ] ) in the control group ( HR , 2.56 [ 95 % CI , 0.68 - 9.60 ] ; P = .14 ; age-adjusted HR , 2.40 [ 95 % CI , 0.62 - 9.22 ] ; P = .20 ) . Five-year DFS was 80.5 % ( 95 % CI , 73.1%-86.1 % ) in the LHRHa group and 83.7 % ( 95 % CI , 76.1%-89.1 % ) in the control group ( LHRHa vs control : HR , 1.17 [ 95 % CI , 0.72 - 1.92 ] ; P = .52 ) . CONCLUSIONS AND RELEVANCE Among premenopausal women with either hormone receptor-positive or hormone receptor-negative breast cancer , concurrent administration of triptorelin and chemotherapy , compared with chemotherapy alone , was associated with higher long-term probability of ovarian function recovery , without a statistically significant difference in pregnancy rate . There was no statistically significant difference in DFS for women assigned to triptorelin and those assigned to chemotherapy alone , although study power was limited . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00311636 OBJECTIVE To determine whether GnRHa administration before and during combination chemotherapy for breast cancer could preserve posttreatment ovarian function in young women or not . DESIGN Prospect i ve r and omized controlled study . SETTING Department of Obstetrics and Gynecology , Mansura University Hospital , Mansura , Egypt . PATIENT(S ) Eighty patients with unilateral adenocarcinoma of the breast and with no metastasis who had undergone modified radical mastectomy or breast-conserving surgery plus full axillary lymph node dissection were included in the study . Patients were assigned r and omly to receive combined GnRHa and chemotherapy or chemotherapy alone . One woman in each group dropped out . MAIN OUTCOME MEASURE(S ) Return of spontaneous menstruation and ovulation . Hormonal changes ( FSH , LH , E(2 ) , P ) during and after the course of treatment . RESULT ( S ) In the study group , 89.6 % resumed menses and 69.2 % resumed spontaneous ovulation within 3 - 8 months of termination of the GnRHa/chemotherapy cotreatment ; 11.4 % experienced hypergonadotrophic amenorrhoea and ovarian failure 8 months after treatment . In the control group ( chemotherapy without GnRHa ) , 33.3 % resumed menses and 25.6 % resumed normal ovarian activity . The median FSH and LH concentrations , 6 months after completion of the GnRHa/chemotherapy cotreatment group , were significantly less than the control group . During the GnRHa/chemotherapy cotreatment the concentrations of FSH , LH , and P decreased to almost prepubertal levels . However , within 1 - 3 months after the last GnRHa injection , an increase in LH and FSH concentrations was detected , followed several weeks later in by an increase in P concentrations to within normal levels . CONCLUSION ( S ) GnRHa administration before and during combination chemotherapy for breast cancer may preserve posttreatment ovarian function in women < 40 years . Long-term studies are required The increased survival of patients with breast cancer has given rise to other problems associated with the complications of chemotherapy . One major complication is premature ovarian failure , an especially harmful outcome for women of reproductive age . This study was performed to evaluate the efficacy of GnRH agonist ( GnRHa ) treatment on protecting ovarian function in young breast cancer patients ( 30.59±5.1 yr ) receiving chemotherapy after surgery . Twenty-two women were enrolled and given subcutaneous injections of leuprolide acetate ( 3.75 mg ) every 4 weeks during chemotherapy . Follow-up laboratory tests ( luteinizing hormone [ LH ] , follicle stimulating hormone [ FSH ] , and estradiol ) were performed 1 , 3 , and 6 months after chemotherapy . Menstruation patterns and clinical symptoms were followed up for a mean duration of 35.6±1.7 months . FSH and LH levels were normal in all patients 6 months after completing chemotherapy ( 8.0±5.3 , 4.4±2.7 mIU/mL , respectively ) . During follow-up , none of the patients complained of menopausal symptoms and 81.8 % experienced recovery of menstruation . This report is the first trial of GnRHa as a treatment modality to protect ovarian function during adjuvant chemotherapy in young Korean breast cancer patients BACKGROUND The reduction of treatment-related toxic effects is the main goal in the current trials of Output:	Evidence , albeit of low quality , supports the use of GnRHa before and /or during chemotherapy to reduce the risk of POI and increase the probability of spontaneous pregnancy in the short term .
MS22550	*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 ( S ) Little is known about the pharmacokinetic ( PK ) properties of gentamicin in newborns undergoing controlled hypothermia after suffering from hypoxic−ischaemic encephalopathy due to perinatal asphyxia . This study prospect ively evaluates and describes the population PK of gentamicin in these patients METHODS Demographic , clinical and laboratory data of patients included in a multicentre prospect i ve observational cohort study ( the ‘ PharmaCool Study ’ ) were collected . A non-linear mixed-effects regression analysis ( nonmem ® ) was performed to describe the population PK of gentamicin . The most optimal dosing regimen was evaluated based on simulations of the final model . RESULTS A total of 47 patients receiving gentamicin were included in the analysis . The PK were best described by an allometric two compartment model with gestational age ( GA ) as a covariate on clearance ( CL ) . During hypothermia the CL of a typical patient ( 3 kg , GA 40 weeks , 2 days post-natal age ( PNA ) ) was 0.06 l kg−1 h−1 ( inter-individual variability ( IIV ) 26.6 % ) and volume of distribution of the central compartment ( Vc ) was 0.46 l kg−1 ( IIV 40.8 % ) . CL was constant during hypothermia and rewarming , but increased by 29 % after reaching normothermia ( > 96 h PNA ) . CONCLUSIONS This study describes the PK of gentamicin in neonates undergoing controlled hypothermia . The 29 % higher CL in the normothermic phase compared with the preceding phases suggests a delay in normalization of CL after rewarming has occurred . Based on simulations we recommend an empiric dose of 5 mg kg−1 every 36 h or every 24 h for patients with GA 36–40 weeks and GA 42 weeks , respectively In an examination of the relationships among plasma aminoglycoside concentrations , the minimal inhibitory concentration ( MIC ) for the infecting organism , and therapeutic outcome , data were analyzed from 236 patients with gram-negative bacterial infections who were participants in four clinical trials of gentamicin , tobramycin , and amikacin . Clinical response to therapy occurred in 188 ( 80 % ) patients . Elevated maximal and mean peak aminoglycoside concentration/MIC ratios were strongly associated with clinical response ( P less than .00001 and P less than .0001 , respectively ) . A grade d dose-response effect was found between an increasing maximal peak concentration/MIC ratio and clinical response . By logistic regression the peak concentration/MIC ratios were associated significantly with clinical response after adjustment for underlying severity of illness and other factors correlated with response . These results demonstrate that a high peak concentration relative to the MIC for the infecting organism is a major determinant of the clinical response to aminoglycoside therapy A prospect i ve case controlled study was conducted in the NICU of a tertiary level referral teaching hospital to determine the incidence of renal failure in asphyxiated neonates and to correlate severity and type of renal failure with Apgar score and hypoxic ischemic encephalopathy ( HIE ) grading of the neonates . Ninety-eight neonates were enrolled 70 asphyxiated babies and 28 healthy controls . Renal functions were assessed using urinary output , urine microscopy , biochemical parameters and sonographic findings . Babies having renal failure were managed on a protocol ised plan and followed up till 6 months of age to detect any residual impairment . Blood urea and serum creatinine were significantly higher in asphyxiated babies compared to the control group . Biochemical derangements correlated well with HIE staging and Apgar scores . There was no significant difference in urine output in the control and the study group as significant oliguria was seen in only 7 of the 70 asphyxiated babies and the output did not correlate with severity of asphyxia . Serum sodium level and fractional excretion of sodium showed significantly different values in the asphyxiated babies compared to control . Of the 70 asphyxiated babies 33 ( 47.1 % ) had renal failure , which was of the non-oliguric type in 78 % cases and oliguric type in 22 % cases . Sonographic abnormalities were seen more often in oliguric babies and was associated with a bad prognosis . Renal parameters normalized in all neonates by 6 months of age . Mortality was higher in babies with oliguric renal failure . We conclude that renal failure is a significant problem in asphyxiated neonates with majority of babies having nonoliguric failure . Severity of renal function abnormality correlates well with degree of asphyxia . Oliguria , hyponatremia and abnormal sonographic scan are bad prognostic signs in renal failure secondary to birth asphyxia Abstract Background and objective : Preterm and term newborn infants show wide interindividual variability ( IIV ) in pharmacokinetic parameters of gentamicin . More extensive knowledge and use of predictive covariates could lead to faster attainment of therapeutic concentrations and a reduced need for concentration monitoring . This study was performed to characterize the population pharmacokinetics of gentamicin in preterm and term neonates and to identify and quantify relationships between patient characteristics and IIV . A secondary aim was to evaluate cystatin C as a marker for gentamicin clearance in this patient population . Methods : Data were collected in a prospect i ve study performed in the Neonatal Intensive Care Unit at the University Children ’s Hospital , Uppsala , Sweden . Population pharmacokinetic modelling was performed using nonlinear mixed-effects modelling ( NONMEM ) software . Bodyweight was included as the primary covariate according to an allometric power model . Other evaluated covariates were age ( postmenstrual age , gestational age [ GA ] , postnatal age [ PNA ] ) , markers for renal function ( serum creatinine , serum cystatin C ) and concomitant medication with cefuroxime , vancomycin or indometacin . Covariate-parameter relationships were explored using a stepwise covariate model building procedure . The predictive performance of the developed model was evaluated using an independent external data set for a similar patient population . Results : Sixty-one newborn infants ( GA range 23.3–42.1 weeks , PNA range 0–45 days ) were enrolled in the study . In total , 894 serum gentamicin sample s were included in the analysis . The concentration-time profile was described using a three-compartment model . Gentamicin clearance increased with the GA and PNA ( included in a nonlinear fashion ) . The GA was also identified as having a significant influence on the central volume of distribution , with a preterm neonate having a larger central volume of distribution per kilogram of bodyweight than a term neonate . Cystatin C and creatinine were not correlated with gentamicin clearance in this study population . The external data set was well predicted by the developed model . Conclusion : Bodyweight and age ( GA and PNA ) were found to be major factors contributing to IIV in gentamicin clearance in neonates . Based on these data , cystatin C and serum creatinine were not correlated with gentamicin clearance and therefore not likely to be predictive markers of renal function in this patient population . Based on predictions from the developed model , preterm neonates do not reach targeted peak and trough gentamicin concentrations after a st and ard dosage regimen of 4 mg/kg given once daily , suggesting a need for higher loading doses and prolonged dosing intervals in this patient population OBJECTIVES To develop and vali date a new risk-of-bias tool for nonr and omized studies ( NRSs ) . STUDY DESIGN AND SETTING We developed the Risk of Bias Assessment Tool for Nonr and omized Studies ( RoBANS ) . A validation process with 39 NRSs examined the reliability ( interrater agreement ) , validity ( the degree of correlation between the overall assessment s of RoBANS and Method ological Index for Nonr and omized Studies [ MINORS ] , obtained by plotting the overall risk of bias relative to effect size and funding source ) , face validity with eight experts , and completion time for the RoBANS approach . RESULTS RoBANS contains six domains : the selection of participants , confounding variables , the measurement of exposure , the blinding of the outcome assessment s , incomplete outcome data , and selective outcome reporting . The interrater agreement of the RoBANS tool except the measurement of exposure and selective outcome reporting domains ranged from fair to substantial . There was a moderate correlation between the overall risks of bias determined using RoBANS and MINORS . The observed differences in effect sizes and funding sources among the assessed studies were not correlated with the overall risk of bias in these studies . The mean time required to complete RoBANS was approximately 10 min . The external experts who were interviewed evaluated RoBANS as a " fair " assessment tool . CONCLUSIONS RoBANS shows moderate reliability , promising feasibility , and validity . The further refinement of this tool and larger validation studies are required OBJECTIVE To define the incidence of hearing impairment , document plasma gentamicin concentrations , and identify factors associated with permanent hearing impairment in infants subjected to therapeutic hypothermia for moderate or severe neonatal encephalopathy . STUDY DESIGN Data were collected prospect ively in a regional center providing therapeutic hypothermia . Cooled infants at ≥ 36 weeks gestation with moderate or severe neonatal encephalopathy were analyzed if a full data set was available ( n = 108 ) , including clinical variables and gentamicin trough levels . Infants with hearing impairment were identified , and survivors were followed up with neurodevelopmental evaluation at age 18 months . Stepwise logistic regression identified factors associated with hearing impairment . RESULTS Nine infants died , and among the survivors , 10.1 % developed a permanent hearing impairment . The trough gentamicin level was above the recommended cutoff of 2 mg/L in 37 % of the infants in the entire cohort and in 90 % of the infants with hearing impairment . Logistic regression analysis identified high trough gentamicin level , low cord pH , and hypoglycemia ( < 46.8 mg/dL ) in the first postnatal hour as significantly associated with hearing impairment . The need for inotropic support was close to significant ( P = .055 ) . CONCLUSION Hearing impairment was a common finding among cooled infants . Plasma gentamicin levels were commonly > 2 mg/L. Based on these findings , we propose changes in gentamicin dosing interval and trough level monitoring to minimize the risk of potentially toxic levels in cooled newborns Two hundred fifty-eight patients with suspected sepsis were treated with tobramycin or gentamicin in a prospect i ve , r and omized , double-blind trial . One hundred forty-six patients received nine or more doses , had serial determinations of serum creatinine , and were evaluated for nephrotoxicity ; 91 were able to cooperate with audiometry and were evaluated for auditory toxicity . Auditory toxicity developed in five of 47 ( 10 per cent ) given gentamicin and five of 44 ( 11 per cent ) given tobramycin . Nephrotoxicity developed in 19 of 72 ( 26 per cent ) given gentamicin and nine of 74 ( 12 per cent ) given tobramycin ( P less than 0.025 ) . The severity of the nephrotoxicity was not different ; the mean increase in creatinine was 1.3 mg per 100 ml ( 114.9 mumol per liter ) in both groups . Both the tobramycin and gentamicin groups had a similar mean age , initial serum creatinine level , total dose , serum aminoglycoside level , and duration of therapy . We conclude that tobramycin causes nephrotoxicity less frequently than does gentamicin BACKGROUND Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy is uncertain . METHODS We performed a r and omized trial of infants who were less than 6 hours of age and had a gestational age of at least 36 weeks and perinatal asphyxial encephalopathy . We compared intensive care plus cooling of the body to 33.5 degrees C for 72 hours and intensive care alone . The primary outcome was death or severe disability at 18 months of age . Prespecified secondary outcomes included 12 neurologic outcomes and 14 other adverse outcomes . RESULTS Of 325 infants enrolled , 163 underwent intensive care with cooling , and 162 underwent intensive care alone . In the cooled group , 42 infants died and 32 survived but had severe neurodevelopmental disability , whereas in the noncooled group , 44 infants died and 42 had severe disability ( relative risk for either outcome , 0.86 ; 95 % confidence interval [ CI ] , 0.68 to 1.07 ; P=0.17 ) . Infants in the cooled group had an increased rate of survival without neurologic abnormality ( relative risk , 1.57 ; 95 % CI , 1.16 to 2.12 ; P=0.003 ) . Among survivors , cooling result ed in reduced risks of cerebral palsy ( relative risk , 0.67 ; 95 % CI , 0.47 to 0.96 ; P=0.03 ) and improved scores on the Mental Developmental Index and Psychomotor Developmental Index of the Bayley Scales of Infant Development II ( P=0.03 for each ) and the Gross Motor Output:	WHAT IS NEW AND CONCLUSION Gentamicin clearance is decreased in neonates with HIE receiving hypothermia treatment compared to those not receiving hypothermia treatment .
MS22551	*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 vitro and animal studies suggest that high concentrations of recombinant human erythropoietin ( rHuEPO ) might divert multipotent progenitors into erythroid maturation at the expense of granulocyte production . We determined whether changes of number and lineage commitment of peripheral blood progenitor cells occur in premature infants during therapy with rHuEPO . Thirty preterm infants were r and omly assigned either to receive 300 IU of eopoetin alpha s.c . per kilogram body weight three times a week for four weeks or to a control group . At study entry and after two weeks of treatment the numbers of circulating BFU-E , granulocyte-macrophage colony-forming units ( CFU-GM ) and granulocyte-erythrocyte-macrophage-megakaryocyte CFU ( CFU-GEMM ) were analyzed by semisolid culture technique , CD34 + cells and early myeloid CD34+CD45RA- progenitors by flow cytometry . As compared with the control group , rHuEPO treatment did not exert any significant modulatory effect on numbers of CFU-GM , nor was there a significant change in numbers of BFU-E , CFU-GEMM , total-CFU , percentage of CD34 + or CD34+CD45RA- cells . Mean neutrophil count was not significantly reduced at any period during the study . Compared with the control group , the infants receiving rHuEPO had higher hematocrit values ( p = 0.003 ) and absolute reticulocyte counts ( p < 0.001 ) . The median cumulative volume of blood transfused per kilogram per day was 0.86 ml ( first quartile 0.5 ml ; third quartile 1.1 ml ) in the control group and 0 ml ( first quartile 0 ml ; third quartile 0.47 ml ) in the rHuEPO group ( p = 0.038 ) . We conclude using a relatively high dose of rHuEPO in premature infants , no significant in vivo effect on circulating peripheral blood progenitor or neutrophil count could be detected In addition to its hematopoietic effects , erythropoietin causes an increased release of endothelin-1 and the stimulation of angiogenesis and thereby it may have possible role in development of retinopathy of prematurity ( ROP ) . Our objective was to determine if an association exists between recombinant human erythropoietin ( rhEPO ) treatment and the development of ROP . Our case-control study involved 85 very low birthweight infants with birthweights < 1500 g born during 2003 and 2004 . All the infants were divided into two groups on the basis of whether they got rhEPO or not . The rhEPO was given at the dose of 200 to 250 units/kg/dose three times a week for 10 doses . Further duration of rhEPO therapy was decided on the basis of the clinical response . Ophthalmological examinations were done at the age of 5 to 6 weeks and were repeated 1 to 4 weeks after the first examination according to the severity of the ROP disease during their in-hospital stay . Of 85 infants , 56 ( 66 % ) received rhEPO and 29 ( 34 % ) did not . In the rhEPO-treated group , 12 infants ( 21 % ) had ROP ; in the non-rhEPO group , 11 infants ( 38 % ) developed ROP . This difference is not statistically significant ( odds ratio = 2.63 ; P = 0.10 ) . There was no correlation between the use of rhEPO and the stage of ROP ( r and om sample = -0.01 ; P = 0.89 ) . There was no significant difference in the incidence of plus , prethreshold , or threshold disease and the treatment required for ROP between the rhEPO-treated and the nontreated group . The study showed there is no significant difference in the incidence and severity of ROP between the rhEPO-treated and nontreated group BACKGROUND : We previously reported decreased transfusions and donor exposures in preterm infants r and omized to Darbepoetin ( Darbe ) or erythropoietin ( Epo ) compared with placebo . As these erythropoiesis-stimulating agents ( ESAs ) have shown promise as neuroprotective agents , we hypothesized improved neurodevelopmental outcomes at 18 to 22 months among infants r and omized to receive ESAs . METHODS : We performed a r and omized , masked , multicenter study comparing Darbe ( 10 μg/kg , 1 × /week subcutaneously ) , Epo ( 400 U/kg , 3 × /week subcutaneously ) , and placebo ( sham dosing 3 × /week ) given through 35 weeks ’ postconceptual age , with transfusions administered according to a st and ardized protocol . Surviving infants were evaluated at 18 to 22 months ’ corrected age using the Bayley Scales of Infant Development III . The primary outcome was composite cognitive score . Assessment s of object permanence , anthropometrics , cerebral palsy , vision , and hearing were performed . RESULTS : Of the original 102 infants ( 946 ± 196 g , 27.7 ± 1.8 weeks ’ gestation ) , 80 ( 29 Epo , 27 Darbe , 24 placebo ) returned for follow-up . The 3 groups were comparable for age at testing , birth weight , and gestational age . After adjustment for gender , analysis of covariance revealed significantly higher cognitive scores among Darbe ( 96.2 ± 7.3 ; mean ± SD ) and Epo recipients ( 97.9 ± 14.3 ) compared with placebo recipients ( 88.7 ± 13.5 ; P = .01 vs ESA recipients ) as was object permanence ( P = .05 ) . No ESA recipients had cerebral palsy , compared with 5 in the placebo group ( P < .001 ) . No differences among groups were found in visual or hearing impairment . CONCLUSIONS : Infants r and omized to receive ESAs had better cognitive outcomes , compared with placebo recipients , at 18 to 22 months . Darbe and Epo may prove beneficial in improving long-term cognitive outcomes of preterm infants ABSTRACT : To assess whether erythropoietin ( EPO ) treatment is safe and reduces the need for transfusion , we r and omized 44 preterm infants to an EPO group and a comparable control ( CON ) group . EPO 150 U/kg was given s.c . twice weekly for 6 wk from the 1st wk of life . Hematologic parameters , transfusion requirements , and growth were followed during therapy and for 6 mo thereafter . To better assess in which neonates EPO treatment was effective , we classified retrospectively the EPO and CON groups into uncomplicated neonates ( EPO A : n = 9 , birth weight = 1247 ± 126 g , gestational age = 29.8 ± 1.5 wk ; CON A : n = 7 , birth weight = 1217 ± 145 g , gestational age = 29.9 ± 1.5 wk ) and neonates requiring artificial ventilation ( EPO B : n = 16 , birth weight = 1169 ± 249 g , gestational age = 28.1 ± 2 wk ; CON B : n = 12 , birth weight = 1173 ± 215 g , gestational age = 28.3 ± 2 wk ) . There were significant differences in reticulocytes between both uncomplicated and ventilated neonates in the EPO group compared with respective control groups . However , the need for transfusion was significantly less in the uncomplicated EPO group ( EPO A : 0.44 ± 0.73 versus CON A : 1.28 ± 0.75 , p < 0.05 ) but not in the neonates on ventilation ( EPO B : 8.25 ± 5 versus CON B : 7.75 ± 3.7 ) . In conclusion , early EPO administration reduces the need for transfusion in uncomplicated premature neonates . Although stimulation of erythropoiesis was apparent in both uncomplicated and complicated neonates , the end- result of increased need for transfusion in complicated neonates was related to altered indication of transfusion . These infants probably require further or longer EPO administration after weaning from ventilation and improvement of clinical condition OBJECTIVE To study the efficacy , safety and cost effectiveness of recombinant human erythropoietin ( r-HuEPO ) in reducing erythrocyte transfusion needs in very low birthweight ( VLBW ) infants . METHODS We conducted a non-blind r and omized controlled trial and assigned 100 VLBW infants , less than 33 weeks gestation , to receive either r-HuEPO 750 U/kg per week subcutaneously from day 5 to day 40 or no erythropoietin ( EPO ) . Infants received oral iron 3 - 6 mg/kg per day from day 10 . Transfusion needs were analysed for all enrolled infants and in five weight subgroups : birthweight of less than 600 g , 600 - 799 g , 800 - 999 g , 1000 - 1199 g and infants more than 1200 g. RESULTS VLBW infants on r-HuEPO attained higher reticulocyte counts and haematocrit than control infants but the mean number of transfusions and volume of erythrocyte transfused per infant were not statistically different . Of infants 800 - 999 g at birth , the mean number of transfusions per infant was 2.1 compared with 3.5 transfusions per control infant ( P = 0.04 ) . Volume of erythrocytes transfused was 34.9 + /- 32.1 mL/kg in r-HuEPO-treated infants and 56.6 + /- 25.8 mL/kg in control infants ( P = 0.03 ) . The cost per patient for transfusion and EPO was S$388 for r-HuEPO recipient and S$438 for control infant . Blood pressure , neutrophil count , platelet count and complications of prematurity were not significantly different in both groups of VLBW infants . CONCLUSION r-HuEPO at 750 U/kg per week stimulates erythropoiesis in VLBW infants but significantly reduces the need for erythrocyte transfusion only in infants weighing 800 - 999 g at birth OBJECTIVE : The purpose of this study was to evaluate the efficacy and safety of erythropoietin in neonatal hypoxic-ischemic encephalopathy ( HIE ) , by using a r and omized , prospect i ve study design . METHODS : A total of 167 term infants with moderate/severe HIE were assigned r and omly to receive either erythropoietin ( N = 83 ) or conventional treatment ( N = 84 ) . Recombinant human erythropoietin , at either 300 U/kg ( N = 52 ) or 500 U/kg ( N = 31 ) , was administered every other day for 2 weeks , starting < 48 hours after birth . The primary outcome was death or disability . Neurodevelopmental outcomes were assessed at 18 months of age . RESULTS : Complete outcome data were available for 153 infants . Nine patients dropped out during treatment , and 5 patients were lost to follow-up monitoring . Death or moderate/severe disability occurred for 35 ( 43.8 % ) of 80 infants in the control group and 18 ( 24.6 % ) of 73 infants in the erythropoietin group ( P = .017 ) at 18 months . The primary outcomes were not different between the 2 erythropoietin doses . Subgroup analyses indicated that erythropoietin improved long-term outcomes only for infants with moderate HIE ( P = .001 ) and not those with severe HIE ( P = .227 ) . No negative hematopoietic side effects were observed . CONCLUSION : Repeated , low-dose , recombinant human erythropoietin treatment reduced the risk of disability for infants with moderate HIE , without apparent side effects OBJECTIVE This is a repeat cohort study in which we sought to determine whether an association of necrotizing enterocolitis ( NEC ) < 48 hours of a packed red blood cells ( PRBC ) transfusion was a prior sampling artifact . STUDY DESIGN All very low birth weight neonates with NEC Stage ≥ IIB admitted over an 18-month period were categorized for NEC : ( 1 ) < 48 hours after a PRBC transfusion ; ( 2 ) unrelated to the timing of PRBCs ; and ( 3 ) never transfused . RESULTS Eight hundred eighty-three admissions over 18 months were review ed ; 256 were very low birth weight that result ed in 36 NEC cases and 25 % were associated with PRBC ( n = 9 ) . PRBC-associated cases had lower birth weight , hematocrit , and rapid onset of signs ( < 5 hours ) . The timing of association of PRBC transfusion and NEC differed from r and om , showing a distribution that was not uniform over time ( χ(2 ) = 170.7 , df = 40 ; P < .000001 ) consistent with the possibility of a causative relationship in certain cases of NEC . Current weight at onset of NEC did not Output:	Early administration of EPO reduces the use of RBC transfusions , the volume of RBCs transfused , and donor exposure after study entry .
MS22552	*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 — Epidemiological studies aim ed at correlating coronary heart disease ( CHD ) with serum ferritin levels have thus far yielded inconsistent results . We hypothesized that a labile iron component associated with non – transferrin-bound iron ( NTBI ) that appears in individuals with overt or cryptic iron overload might be more suitable for establishing correlations with CHD . Methods and Results — We investigated the relation of NTBI , serum iron , transferrin saturation , and serum ferritin with risk of CHD and acute myocardial infa rct ion ( AMI ) . The cohort used comprised a population -based sample of 11 471 postmenopausal women aged 49 to 70 years at enrollment in 1993 to 1997 . During a median follow-up of 4.3 years ( quartile limits Q1 to Q3 : 3.3 to 5.4 ) , 185 CHD events were identified , including 66 AMI events . We conducted a case-cohort study using all CHD cases and a r and om sample from the baseline cohort ( n=1134 ) . A weighted Cox proportional hazards model was used to estimate hazard ratios for tertiles of iron variables in relation to CHD and AMI . Adjusted hazard ratios of women in the highest NTBI tertile ( range 0.38 to 3.51 ) compared with the lowest ( range −2.06 to −0.32 ) were 0.84 ( 95 % confidence interval 0.61 to 1.16 ) for CHD and 0.47 ( 95 % confidence interval 0.31 to 0.71 ) for AMI . The results were similar for serum iron , transferrin saturation , and serum ferritin . Conclusions — Our results show no excess risk of CHD or AMI within the highest NTBI tertile compared with the lowest but rather seem to demonstrate a decreased risk . Additional studies are warranted to confirm our findings BACKGROUND Iron deficiency may impair aerobic performance . This study aim ed to determine whether treatment with intravenous iron ( ferric carboxymaltose ) would improve symptoms in patients who had heart failure , reduced left ventricular ejection fraction , and iron deficiency , either with or without anemia . METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association ( NYHA ) functional class II or III , a left ventricular ejection fraction of 40 % or less ( for patients with NYHA class II ) or 45 % or less ( for NYHA class III ) , iron deficiency ( ferritin level < 100 microg per liter or between 100 and 299 microg per liter , if the transferrin saturation was < 20 % ) , and a hemoglobin level of 95 to 135 g per liter . Patients were r and omly assigned , in a 2:1 ratio , to receive 200 mg of intravenous iron ( ferric carboxymaltose ) or saline ( placebo ) . The primary end points were the self-reported Patient Global Assessment and NYHA functional class , both at week 24 . Secondary end points included the distance walked in 6 minutes and the health-related quality of life . RESULTS Among the patients receiving ferric carboxymaltose , 50 % reported being much or moderately improved , as compared with 28 % of patients receiving placebo , according to the Patient Global Assessment ( odds ratio for improvement , 2.51 ; 95 % confidence interval [ CI ] , 1.75 to 3.61 ) . Among the patients assigned to ferric carboxymaltose , 47 % had an NYHA functional class I or II at week 24 , as compared with 30 % of patients assigned to placebo ( odds ratio for improvement by one class , 2.40 ; 95 % CI , 1.55 to 3.71 ) . Results were similar in patients with anemia and those without anemia . Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality -of-life assessment s. The rates of death , adverse events , and serious adverse events were similar in the two study groups . CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency , with or without anemia , improves symptoms , functional capacity , and quality of life ; the side-effect profile is acceptable . ( Clinical Trials.gov number , NCT00520780 ) The ' iron hypothesis ' cl aims that Fe depletion protects against IHD . The objective of the present study was to investigate the associations between serum ferritin levels and the risk of CVD and IHD in a population -based sample . A total of 2874 subjects with serum ferritin levels between 15 and 300 microg/l from the Danish part of the ' Monitoring of Trends and Determinants in Cardiovascular Disease ' ( DAN-MONICA ) I study and the 1914 Cohort survey were followed for 10 years . Information on behavioural and socio-demographic characteristics were collected and serum ferritin levels measured . Non-fatal and fatal CVD and IHD were identified by the International Classification of Diseases diagnoses numbers . Multivariable Cox proportional hazard regression models with restricted cubic splines were performed . During the follow-up period , 310 subjects ( 201 men ; 109 women ) and 161 subjects ( 117 men ; forty-four women ) experienced CVD and IHD , respectively . Our analyses revealed no statistically significant associations between serum ferritin levels and the risk of CVD or IHD in both sexes . However , in women , the results argue for a U-shaped relationship between serum ferritin levels and CVD as well as IHD . In concordance with former prospect i ve studies , the present results do not support the hypothesis that normal body Fe stores should play a significant role in the development of CVD BACKGROUND In a recent Finnish study , ferritin was suggested to be an independent risk factor for acute myocardial infa rct ion . This study suggested that high levels of iron stores might thus be atherogenic and possibly explain partly the sex difference in the incidence of ischemic heart disease . METHODS AND RESULTS A r and omly selected group ( n = 2036 ) , men and women aged 25 to 74 years , were examined between June and September 1983 . All classic risk factors for coronary artery disease were measured as well as basic hematologic parameters and the parameters of iron metabolism , ie , iron , total iron-binding capacity ( TIBC ) , and ferritin . During the follow-up for 8.5 years , 81 subjects experienced acute myocardial infa rct ion ( 63 men and 18 women ) . The differences in the iron parameters between men and women were almost exclusively seen in ferritin values ( 198 micrograms/L in men and 91 micrograms/L in women ) , whereas small differences were seen in TIBC . The Cox proportional hazards model was used to estimate the contribution of independent variables to the risk of myocardial infa rct ion . TIBC was found to be a strong independent negative risk factor in men ( RR = 0.95 ; 95 % CI , 0.92 to 0.98 ) , whereas ferritin ( RR = 0.999 ; 95 % CI , 0.997 to 1.001 ) or other iron parameters had no significant predictive power . Each increase in TIBC of 1 mumol/L was associated with a 5.1 % decrease in the risk of myocardial infa rct ion . The classic major risk factors , ie , blood pressure , smoking , total cholesterol , and high-density lipoprotein , had significant independent correlation with myocardial infa rct ion . When Cox multivariate analysis was carried out on both sexes combined , TIBC was still an independent negative risk factor , and the logarithmic transform of ferritin had a weak negative correlation but was not statistically significant . Sex was in this group still a very strong risk factor after taking into account all classic risk factors as well as the parameters of iron metabolism . CONCLUSIONS This study suggests that transferrin , measured as TIBC , is an independent negative risk factor for myocardial infa rct ion . Other parameters of iron metabolism , including ferritin , were not found to contribute to the risk The positive association between body iron stores and risk of coronary heart disease ( CHD ) initially observed among a Finnish male population has not been corroborated by studies conducted in other population s. The soluble transferrin receptor (sTfR):ferritin ratio has been suggested to be a better index than ferritin to measure body iron stores . Because sTfR is sensitive to iron deficiency , this ratio can distinguish individuals with similar ferritin levels with respect to their iron status . To evaluate this novel index in relation to CHD risk , we prospect ively identified and confirmed 242 incident CHD cases and r and omly selected 483 controls matched for age , smoking , and fasting status among women that provided blood sample s in the Nurses ' Health Study during 9 y of follow-up . In both crude and multivariate analyses , neither the sTfR : ferritin ratio nor ferritin was significantly associated with an elevated risk of CHD . After multivariate adjustment for established and potential CHD risk factors , compared with women in the lowest quartile of the sTfR : ferritin ratio , women in the 2nd to 4th quartiles had relative risks ( RR ) ( 95 % CI ) of 1.39 ( 0.82 , 2.36 ) , 1.12 ( 0.66 , 1.91 ) , and 1.13 ( 0.65 , 1.97 ; P-trend = 0.61 ) , respectively . The multivariate RR ( 95 % CI ) for ferritin were 1.05 ( 0.62 , 1.77 ) , 1.19 ( 0.69 , 2.03 ) , and 1.05 ( 0.60 , 1.85 ; P-trend = 0.90 ) across quartiles . Our data do not support the hypothesis that excessive body iron stores are associated with risk of CHD OBJECTIVE Our specific aim in the prospect i ve , longitudinal assessment of 8,251 subjects in the National Health and Nutrition Examination Survey , NHANES I , followup study was to assess the important roles of modifiable dietary and behavioral characteristics in the causation and prevention of coronary heart disease ( CHD ) . METHODS Using NHANES I prospect i ve 10 year followup data , we studied 8,251 subjects ; 492 with cardiovascular events and 7,759 without events during the followup period ( 1971 - 75 to 1982 - 84 ) . Using general linear models and logistic regression , we assessed the relationships of CHD risk factors to CHD morbidity and mortality . RESULTS By logistic regression , the following factors were independently , significantly , and inversely associated with coronary heart and vascular disease deaths and hospitalizations : alcohol intake , dietary riboflavin , dietary iron , serum magnesium , leisure time exercise , habitual physical activity , and female gender . Positive significant independent determinants of CHD events included cigarette smoking , sedimentation rate , Quetelet index , maximum body weight , and age . CONCLUSIONS These associations emphasize the important role of modifiable dietary and behavioral characteristics in the causation and prevention of CHD BACKGROUND Iron has been suggested to play a role in the development of cardiovascular disease ( CVD ) through its pro-oxidant properties . However , epidemiological studies on iron status and the risk of CVD have yielded conflicting results . We therefore carried out a prospect i ve study to evaluate the relationship between iron status and CVD in a middle-aged French population . METHODS In total , 9917 subjects ( 3223 men aged 45 - 60 years and 6694 women aged 35 - 60 years ) included in the SU.VI.MAX ( SUpplementation en VItamines et Minéraux AntioXydants ) cohort were followed prospect ively for 7.5 years . All cases of ischaemic heart disease ( IHD ) were identified and vali date d. CVD risk factors , haemoglobin and serum ferritin concentrations were measured at baseline . FINDINGS Of men 4.3 % , and of women 37.8 % , presented at baseline a serum ferritin concentration < 30 microg l(-1 ) . During the follow-up , 187 subjects ( 148 men , 39 women ) developed IHD . Serum ferritin was positively associated with total cholesterol , serum triglycerides , systolic and diastolic blood pressure , body mass index and haemoglobin . No linear association was found between serum ferritin and IHD risk in men or in women . CONCLUSION Our data do not support a major role of iron status in the development of IHD in a healthy general population BACKGROUND We prospect ively studied iron intake in relation to the incidence of coronary disease in a 4-year follow-up of 44,933 men ( with no previous history of cardiovascular disease ) aged 40 to 75 years in 1986 who completed a food frequency question naire at baseline . METHODS AND RESULTS We documented 844 incident cases of coronary disease ( 249 nonfatal myocardial infa rct ions , 137 coronary disease fatalities , and 458 bypass operations or angioplasties ) . After adjustment for established risk factors , there was no significant association between total iron intake and risk of coronary heart disease . Men in the highest quintile of total intake ( median , 37 mg/d ) had a relative risk ( RR ) of fatal coronary disease or nonfatal myocardial infa rct ion of 0.73 ( 9 Output:	The most likely scenario that emerges from the available studies is that , in the reference range , iron status has a neutral effect . Extreme conditions of iron deficiency , as well as of iron overload , are associated with modestly increased CVD risk , although with different proposed mechanisms
MS22553	*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 purpose of our study was to organize the literature regarding the efficacy of modern videolaryngoscopes in oral endotracheal intubation , then perform a quality assessment according to recommended external criteria and make recommendations for use . Methods Inclusion criteria included devices with recent studies of human subjects . A total of 980 articles were returned in the initial search and 65 additional items were identified using cited references . After exclusion of articles failing to meet study criteria , 77 articles remained . Data were extracted according to the rate of successful intubation and improvement of glottic view compared with direct laryngoscopy . Studies were classified according to whether they primarily examined subjects with normal airways , possessing risk factors for difficult direct laryngoscopy , or following difficult or failed direct laryngoscopy . Results The evidence of efficacy for videolaryngoscopy in the difficult airway is limited . What evidence exists is both r and omized prospect i ve and observational in nature , requiring a scheme that evaluates both forms and allows recommendations to be made . Conclusions In patients at higher risk of difficult laryngoscopy we recommend the use of the Airtraq , CTrach , GlideScope , Pentax AWS and V-MAC to achieve successful intubation . In difficult direct laryngoscopy ( C&L > /= 3 ) we cautiously recommend the use of the Airtraq , Bonfils , Bullard , CTrach , GlideScope , and Pentax AWS , by an operator with reasonable prior experience , to achieve successful intubation when used in accordance with the ASA practice guidelines for management of the difficult airway . There is additional evidence to support the use of the Airtraq , Bonfils , CTrach , GlideScope , McGrath , and Pentax AWS following failed intubation via direct laryngoscopy to achieve successful intubation . Future investigation would benefit from precise qualification of the subjects under study , and an improvement in overall methodology to include r and omization and blinding Background For patients suspicious of cervical spine injury , a Philadelphia cervical collar is usually applied . Application of Philadelphia cervical collar may cause difficult airway . The aim of this study was to evaluate the laryngeal view and the success rate at first intubation attempt of the Airtraq and conventional laryngoscopy in patients with simulated cervical spine injury after application of a Philadelphia cervical collar . Methods Anesthesia was induced with propofol , remifentanil , and rocuronium . After a Philadelphia cervical collar applied , patients were r and omly assigned to tracheal intubation with an Airtraq ( Group A , n = 25 ) or with conventional laryngoscopy ( Group L , n = 25 ) . Measurements included intubation time , success rate of first intubation attempt , number of intubation attempts , and percentage of glottic opening ( POGO ) score . Mean blood pressure and heart rate were also recorded at baseline , just before and after intubation . Results The success rate of the first attempt in Group A ( 96 % ) was significantly greater than with the Group L ( 40 % ) . POGO score was significantly greater in Group A ( 84 ± 20 % ) than in Group L ( 6 ± 11 % ) . The duration of successful intubation at first tracheal intubation attempt and hemodynamic changes were not significantly different between the two groups . Conclusions The Airtraq offers a better laryngeal view and higher success rate at first intubation attempt in patients who are applied with a Philadelphia cervical collar due to suspicion of cervical spine injury The Airtraq ® laryngoscope is a novel single use tracheal intubation device . We compared the Airtraq ® with the Macintosh laryngoscope in patients deemed at low risk for difficult intubation in a r and omised , controlled clinical trial . Sixty consenting patients presenting for surgery requiring tracheal intubation were r and omly allocated to undergo intubation using a Macintosh ( n = 30 ) or Airtraq ® ( n = 30 ) laryngoscope . All patients were intubated by one of four anaesthetists experienced in the use of both laryngoscopes . No significant differences in demographic or airway variables were observed between the groups . All but one patient , in the Macintosh group , was successfully intubated on the first attempt . There was no difference between groups in the duration of intubation attempts . In comparison to the Macintosh laryngoscope , the Airtraq ® result ed in modest improvements in the intubation difficulty score , and in ease of use . Tracheal intubation with the Airtraq ® result ed in less alterations in heart rate . These findings demonstrate the utility of the Airtraq ® laryngoscope for tracheal intubation in low risk patients Background : The Glide Scope videolaryngoscope provides a suitable view for intubation , with less force required . Objectives : The present study was conducted , to compare postoperative sore throat and hoarseness after laryngoscopy and intubation , by Macintosh blade or Glide Scope video laryngoscope in normal airway patients . Patients and Methods : Three hundred patients were r and omly allocated into two groups of 150 : Macintosh blade laryngoscope or Glide Scope video laryngoscope . The patients were evaluated for 48 hours for sore throat and hoarseness by an interview . Results : The incidence and severity of sore throat in the Glide Scope group , at 6 , 24 and 48 hours after the operation , were significantly lower than in the Macintosh laryngoscope group . In addition , the incidence of hoarseness in the Glide Scope group , at 6 and 24 hours after the operation , were significantly lower than in the Macintosh laryngoscope group . The incidence and severity of sore throat in men , at 6 and 24 hours after the operation , were significantly lower than in the women . Conclusions : The incidence and severity of sore throat and hoarseness after tracheal intubation by Glide Scope were lower than in the Macintosh laryngoscope . The incidence and severity of sore throat were increased by intubation and longer operation times Endotracheal intubation involving conventional laryngoscopy elicits a haemodynamic response associated with increased heart and blood pressure . The study was aim ed to see if video laryngoscopy and endotracheal intubation has any advantages over conventional laryngoscopy and endotracheal intubation in patients with coronary artery disease . Thirty patients suffering from coronary artery disease scheduled for elective coronary artery bypass grafting ( CABG ) were studied . The patients were r and omly allocated to undergo either conventional laryngoscopy ( group A ) or video laryngoscopy ( group B ) . The time taken to perform endotracheal intubation and haemodynamic changes associated with intubation were noted in both the groups at different time points . The duration of laryngoscopy and intubation was significantly longer in group B ( video laryngoscopy ) when compared to group A patients . However , haemodynamic changes were no different between the groups . There were no events of myocardial ischaemia as monitored by surface electrocardiography during the study period in either of the groups . In conclusion , video laryngoscopy did not provide any benefit in terms of haemodynamic response to laryngoscopy and intubation in patients undergoing primary CABG with a Mallampatti grade of < 2 Background : In the emergency trauma situation , in‐line stabilization ( ILS ) of the cervical spine is used to reduce head and neck extension during laryngoscopy . The Bullard laryngoscope may result in less cervical spine movement than the Macintosh laryngoscope . The aim of this study was to compare cervical spine extension ( measured radiographically ) and time to intubation with the Bullard and Macintosh laryngoscopes during a simulated emergency with cervical spine pre caution s taken . Methods : Twenty‐nine patients requiring general anesthesia and endotracheal intubation were studied . Patients were placed on a rigid board and anesthesia was induced . Laryngoscopy was performed on four occasions : with the Bullard and Macintosh laryngoscope both with and without manual ILS . Cricoid pressure was applied with ILS . To determine cervical spine extension , radiographs were exposed before and during laryngoscopy . Times to intubation and grade view of the larynx were also compared . Results : Cervical spine extension ( occiput‐C5 ) was greatest with the Macintosh laryngoscope ( 25.9 [ degree sign ] + /‐ 2.8 [ degree sign ] ) . Extension was reduced when using the Macintosh laryngoscope with ILS ( 12.9 + /‐ 2.1 [ degree sign ] ) and the Bullard laryngoscope without stabilization ( 12.6 + /‐ 1.8 [ degree sign ] ; P < 0.05 ) . Times to intubation were similar for the Macintosh laryngoscope with ILS ( 20.3 + /‐ 12.8 s ) and for the Bullard without ILS ( 25.6 + /‐ 10.4 s ) . Manual ILS with the Bullard laryngoscope results in further reduction in cervical spine extension ( 5.6 + /‐ 1.5 [ degree sign ] ) but prolongs time to intubation ( 40.3 + /‐ 19.5 s ; P < 0.05 ) . Conclusions : Cervical spine extension and time to intubation are similar for the Macintosh laryngoscope with ILS and the Bullard laryngoscope without ILS . However , time to intubation is significantly prolonged when the Bullard laryngoscope is used in a simulated emergency with cervical spine pre caution s taken . This suggests that the Bullard laryngoscope may be a useful adjunct to intubation of patients with potential cervical spine injury when time to intubation is not critical BACKGROUND The purpose of this study was to evaluate the effectiveness of the Pentax AWS , Glidescope , and the Truview EVO2 , in comparison with the Macintosh laryngoscope , when performing tracheal intubation in patients with neck immobilization using manual in-line axial cervical spine stabilization . METHODS One hundred and twenty consenting patients presenting for surgery requiring tracheal intubation were r and omly assigned to undergo intubation using a Macintosh ( n=30 ) , Glidescope ( n=30 ) , Truview EVO2 ( n=30 ) , or AWS ( n=30 ) laryngoscope . All patients were intubated by one of the three anaesthetists experienced in the use of each laryngoscope . RESULTS The Glidescope , AWS , and Truview EVO2 each reduced the intubation difficulty score ( IDS ) , improved the Cormack and Lehane glottic view , and reduced the need for optimization manoeuvres , compared with the Macintosh . The mean IDS was significantly lower with the Glidescope and AWS compared with the Truview EVO2 device , and the IDS was lowest with the AWS . The duration of tracheal intubation attempts was significantly shorter with the Macintosh compared with the other devices . There were no differences in success rates between the devices tested . The AWS produced the least haemodynamic stimulation . CONCLUSIONS The Glidescope and AWS laryngoscopes required more time but reduced intubation difficulty and improved glottic view over the Macintosh laryngoscope more than the Truview EVO2 laryngoscope when used in patients undergoing cervical spine immobilization We performed a r and omised trial comparing the CEL‐100 videolaryngoscopeTM with the Macintosh laryngoscope blade in 170 patients undergoing double‐lumen tube placement for thoracic surgery . Compared with the Macintosh laryngoscope blade , use of the CEL‐100 result ed in significantly more patients with a Cormack and Lehane Grade ‐1 laryngeal view ( 90.4 % vs 61.0 % , p < 0.001 ) , a higher rate of successful intubation on the first attempt ( 92.8 % vs 79.3 % , p = 0.012 ) , a lower median ( IQR [ range ] ) intubation difficulty score ( 0 ( 0–0 [ 0–60 ] ) vs 15 ( 0–30 [ 0–80 ] ) , p < 0.001 ) , a higher incidence of correct positioning of the tube ( 90.3 % vs 79.2 % , p = 0.041 ) and significantly fewer patients requiring external laryngeal pressure ( 19.3 % vs 32.9 % , p = 0.046 ) . Median ( IQR [ range ] ) time to successful intubation was 45 ( 38–55 [ 22–132 ] ) s with the CEL‐100 compared with 51 ( 40–61 [ 30–160 ] s using the Macintosh laryngoscope blade . We conclude that the CEL‐100 videolaryngoscope is superior to the Macintosh laryngoscope blade for double‐lumen tube insertion Background : The Truview EVO2(C ) laryngoscope ( TL ) is a recently introduced optical device design ed to provide an unmagnified anterior image of the glottic opening and allow indirect laryngoscopy . Aim : This study is design ed to determine whether the TL is a better alternative to the Macintosh laryngoscope ( ML ) for routine endotracheal intubations in patients with usual airway characteristics . Methods : We compared the Truview EVO2(C ) and MLs in 140 elective surgical patients requiring general anaesthesia and intubation in a prospect i ve crossover fashion . The two blades were compared in terms of Cormack and Lehane grade s , time required for intubation , anaesthetists ’ assessment of ease of intubation , intubation difficulty score , attempts at intubation , success rate , soft tissue damage and arterial oxygen saturation during laryngoscopy . The Output:	Videolaryngoscopes may reduce the number of failed intubations , particularly among patients presenting with a difficult airway . They improve the glottic view and may reduce laryngeal/airway trauma . Currently , no evidence indicates that use of a VLS reduces the number of intubation attempts or the incidence of hypoxia or respiratory complications , and no evidence indicates that use of a VLS affects time required for intubation
MS22554	*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 home-based telecare ( TC ) is utilised to manage risks of independent living and provide prompt emergency responses . This study examined the effect of TC on health-related quality of life ( HRQoL ) , anxiety and depressive symptoms over 12 months in patients receiving social care . DESIGN a study of participant-reported outcomes [ the Whole Systems Demonstrator ( WSD ) Telecare Question naire Study ; baseline n = 1,189 ] was nested in a pragmatic cluster-r and omised trial of TC ( the WSD Telecare trial ) , held across three English Local Authorities . General practice ( GP ) was the unit of r and omisation and TC was compared with usual care ( UC ) . METHODS participant-reported outcome measures were collected at baseline , short-term ( 4 months ) and long-term ( 12 months ) follow-up , assessing generic HRQoL , anxiety and depressive symptoms . Primary intention-to-treat analyses tested treatment effectiveness and were conducted using multilevel models to control for GP clustering and covariates for participants who completed question naire measures at baseline assessment plus at least one other assessment ( n = 873 ) . RESULTS analyses found significant differences between TC and UC on Short Form-12 mental component scores ( P < 0.05 ) , with parameter estimates indicating being a member of the TC trial-arm increases mental component scores ( UC-adjusted mean = 40.52 ; TC-adjusted mean = 43.69 ) . Additional significant analyses revealed , time effects on EQ5D ( decreasing over time ) and depressive symptoms ( increasing over time ) . CONCLUSIONS TC potentially contributes to the amelioration in the decline in users ' mental HRQoL over a 12-month period . TC may not transform the lives of its users , but it may afford small relative benefits on some psychological and HRQOL outcomes relative to users who only receive UC . International St and ard R and omised Controlled Trial Number Register : IS RCT N 43002091 BACKGROUND Mild frailty or pre-frailty is common and yet is potentially reversible . Preventing progression to worsening frailty may benefit individuals and lower health/social care costs . However , we know little about effective approaches to preventing frailty progression . OBJECTIVES ( 1 ) To develop an evidence - and theory-based home-based health promotion intervention for older people with mild frailty . ( 2 ) To assess feasibility , costs and acceptability of ( i ) the intervention and ( ii ) a full-scale clinical effectiveness and cost-effectiveness r and omised controlled trial ( RCT ) . DESIGN Evidence review s , qualitative studies , intervention development and a feasibility RCT with process evaluation . INTERVENTION DEVELOPMENT Two systematic review s ( including systematic search es of 14 data bases and registries , 1990 - 2016 and 1980 - 2014 ) , a state-of-the-art review ( from inception to 2015 ) and policy review identified effective components for our intervention . We collected data on health priorities and potential intervention components from semistructured interviews and focus groups with older people ( aged 65 - 94 years ) ( n = 44 ) , carers ( n = 12 ) and health/social care professionals ( n = 27 ) . These data , and our evidence review s , fed into development of the ' HomeHealth ' intervention in collaboration with older people and multidisciplinary stakeholders . ' HomeHealth ' comprised 3 - 6 sessions with a support worker trained in behaviour change techniques , communication skills , exercise , nutrition and mood . Participants addressed self-directed independence and well-being goals , supported through education , skills training , enabling individuals to overcome barriers , providing feedback , maximising motivation and promoting habit formation . FEASIBILITY RCT Single-blind RCT , individually r and omised to ' HomeHealth ' or treatment as usual ( TAU ) . SETTING Community setting s in London and Hertfordshire , UK . PARTICIPANTS A total of 51 community-dwelling adults aged ≥ 65 years with mild frailty . MAIN OUTCOME MEASURES Feasibility - recruitment , retention , acceptability and intervention costs . Clinical and health economic outcome data at 6 months included functioning , frailty status , well-being , psychological distress , quality of life , capability and NHS and societal service utilisation/costs . RESULTS We successfully recruited to target , with good 6-month retention ( 94 % ) . Trial procedures were acceptable with minimal missing data . Individual r and omisation was feasible . The intervention was acceptable , with good fidelity and modest delivery costs ( £ 307 per patient ) . A total of 96 % of participants identified at least one goal , which were mostly exercise related ( 73 % ) . We found significantly better functioning ( Barthel Index + 1.68 ; p = 0.004 ) , better grip strength ( + 6.48 kg ; p = 0.02 ) , reduced psychological distress ( 12-item General Health Question naire -3.92 ; p = 0.01 ) and increased capability-adjusted life-years [ + 0.017 ; 95 % confidence interval ( CI ) 0.001 to 0.031 ] at 6 months in the intervention arm than the TAU arm , with no differences in other outcomes . NHS and carer support costs were variable but , overall , were lower in the intervention arm than the TAU arm . The main limitation was difficulty maintaining outcome assessor blinding . CONCLUSIONS Evidence is lacking to inform frailty prevention service design , with no large-scale trials of multidomain interventions . From stakeholder/public perspectives , new frailty prevention services should be personalised and encompass multiple domains , particularly socialising and mobility , and can be delivered by trained non-specialists . Our multicomponent health promotion intervention was acceptable and delivered at modest cost . Our small study shows promise for improving clinical outcomes , including functioning and independence . A full-scale individually RCT is feasible . FUTURE WORK A large , definitive RCT of the HomeHealth service is warranted . STUDY REGISTRATION This study is registered as PROSPERO CRD42014010370 and Current Controlled Trials IS RCT N11986672 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 21 , No. 73 . See the NIHR Journals Library website for further project information Background : Achieving earlier stage diagnosis is one option for improving lung cancer outcomes in the United Kingdom . Patients with lung cancer typically present with symptoms to general practitioners several times before referral or investigation . Methods : We undertook a mixed methods feasibility individually r and omised controlled trial ( the ELCID trial ) to assess the feasibility and inform the design of a definitive , fully powered , UK-wide , Phase III trial of lowering the threshold for urgent investigation of suspected lung cancer . Patients over 60 , with a smoking history , presenting with new chest symptoms to primary care , were eligible to be r and omised to intervention ( urgent chest X-ray ) or usual care . Results : The trial design and material s were acceptable to GPs and patients . We r and omised 255 patients from 22 practice s , although the proportion of eligible patients who participated was lower than expected . Survey responses ( 89 % ) , and the fidelity of the intervention ( 82 % patients X-rayed within 3 weeks ) were good . There was slightly higher anxiety and depression in the control arm in participants aged > 75 . Three patients ( 1.2 % ) were diagnosed with lung cancer . Conclusions : We have demonstrated the feasibility of individually r and omising patients at higher risk of lung cancer , to a trial offering urgent investigation or usual care Background This study explored the effectiveness of a pro-active , integrated care model for community-dwelling frail older people compared to care as usual by evaluating the effects on a comprehensive set of outcomes : health outcomes ( experienced health , mental health and social functioning ) ; functional abilities ; and quality of life ( general , health-related and well-being ) . Methods The design of this study was quasi-experimental . In this study , 184 frail older patients of three GP practice s that implemented the Walcheren Integrated Care Model were compared with 193 frail older patients of five GP practice s that provided care as usual . In the Walcheren Integrated Care Model , community-dwelling elderly were pro-actively screened for frailty from the GP practice using the Groningen Frailty Indicator , and care needs were assessed with the EASYcare instrument . The GP practice functioned as single entry point from which case management was provided , and the GP was the coordinator of care . The entire process was supported by multidisciplinary meetings , multidisciplinary protocol s and web-based patient files . The outcomes of this study were obtained at baseline , after 3 months and after 12 months and analyzed with linear mixed models of repeated measures . Results The Walcheren Integrated Care Model had a positive effect on love and friendship and a moderately positive effect on general quality of life . The ability to receive love and friendship and general quality of life decreased in the control group but was preserved in the experimental group . No significant differences were found on health outcomes such as experienced health , mental health , social functioning and functional abilities . Conclusions The results indicated that pro-active , integrated care can be beneficial for frail older people in terms of quality of life and love and friendship but not in terms of health outcomes and functional abilities . Recommendations for future research are to gain greater insight into what specific outcomes can be achieved with proactive and integrated care , considering the specific content of this care , and to allow for the heterogeneity of frail older people in evaluation research .Trial registration Current Controlled Trials IS RCT N05748494 . Registration date : 14/03/2013 Background Lifestyle factors represent prime targets for behaviour change interventions to promote healthy ageing and reduce dementia risk . We evaluated a goal - setting intervention aim ed at promoting increased cognitive and physical activity and improving mental and physical fitness , diet and health . Methods This was a pilot r and omised controlled trial design ed to guide planning for a larger-scale investigation , provide preliminary evidence regarding efficacy , and explore feasibility and acceptability . Primary outcomes were engagement in physical and cognitive activity . Participants aged over 50 living independently in the community were recruited through a community Agewell Centre . Following baseline assessment participants were r and omly allocated to one of three conditions : control ( IC ) had an interview in which information about activities and health was discussed ; goal - setting ( GS n = 24 ) had an interview in which they set behaviour change goals relating to physical , cognitive and social activity , health and nutrition ; and goal - setting with mentoring ( GM , n = 24 ) had the goal - setting interview followed by bi-monthly telephone mentoring . Participants and research ers were blinded to group assignment . Participants were reassessed after 12 months . Results Seventy-five participants were r and omised ( IC n = 27 , GS n = 24 , GM n = 24 ) . At 12-month follow-up , the two goal - setting groups , taken together ( GS n = 21 , GM n = 22 ) , increased their level of physical ( effect size 0.37 ) and cognitive ( effect size 0.15 ) activity relative to controls ( IC n = 27 ) . In secondary outcomes , the two goal - setting groups taken together achieved additional benefits compared to control ( effect sizes ≥ 0.2 ) in memory , executive function , cholesterol level , aerobic capacity , flexibility , balance , grip strength , and agility . Adding follow-up mentoring produced further benefits compared to goal - setting alone ( effect sizes ≥ 0.2 ) in physical activity , body composition , global cognition and memory , but not in other domains . Implementation of the recruitment procedure , assessment and intervention was found to be feasible and the approach taken was acceptable to participants , with no adverse effects . Conclusions A brief , low-cost goal - setting intervention is feasible and acceptable , and has the potential to achieve increased activity engagement . Trial registration Current Controlled Trials IS RCT Abstract Purpose : To evaluate the impact of a person-centred , community rehabilitation service on outcomes for people with a neurological condition , in the first year of service . Method : A prospect i ve , observational , pre-post study was conducted with 206 people who had a neurological condition and attended the rehabilitation service to restore function ( e.g. , Stroke ) ; maximize recovery in an ongoing situation ( e.g. , Spina Bifida ) ; or maximize function and independence while preparing for inevitable decline ( e.g. , Parkinson ’s Disease ) . Outcomes were measured via self-report question naires , prior to , and following three months of rehabilitation . The primary outcome was achievement of self-identified goals , measured by the Patient-Specific Functional scale . Secondary outcomes included the Lawton Instrumental Activities of Daily Living ( IADL ) scale , EQ-5D-5L European Quality of Life scale , and ICECAP-O – Index of Capability for Older Adults and health and medical re source use . Results : Participants demonstrated significant goal achievement and a significant reduction in health and medical re source use . There were small positive changes in the Lawton IADL , EQ-5D-5L , and ICECAP-O however these changes were not significant . Conclusions : In the first year of operation , the community rehabilitation service made a significant impact on outcomes for individuals with a neurological condition . Further research is required to identify appropriate measures of activities of daily living and quality of life that reflect person-centred rehabilitation outcomes for restoring function , maximizing function , or preparing for functional decline . Implication s for Rehabilitation Self-identified goals are an important guide for achievement of meaningful outcomes for individuals with a neurological condition . Person-centred outcome measures are required to evaluate the benefits of a Output:	The ICECAP-O has good construct validity and responsiveness , but there is evidence of some issues relating to content validity . Conclusion Focus , in terms of publications , appears to have shifted now from assessment of psychometric properties to the utilisation of the ICECAP-O within economic evaluation .
MS22555	*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: Effects of nutritional supplements on minimizing weight loss and abnormalities of protein turnover during pulmonary exacerbations in cystic fibrosis ( CF ) were studied by controlled trial . Patients received pulmonary therapy and either st and ard diet ( n = 10 ) or adjunctive enteral supplements ( n = 12 ) . Initial protein turnover , measured by [15N]glycine kinetics , showed alterations of protein synthesis ( P Syn ) and catabolism ( P Cat ) , which correlated with the degree of underweight , and negligible net protein deposition ( P Dep ) . With treatment both groups had significant increases in mean body weight and forced expiratory volume in 1 s , expressed as percent predicted value for height ( FEV1 ) by 3 wk , but a significant correlation between initial underweight and subsequent weight gain was observed only in supplemented patients . Mean P Syn and P Dep increased significantly ( p less than 0.001 ) only in the supplemented group . Pulmonary exacerbations in CF have important adverse effects on body-protein metabolism , similar to changes in protein-energy malnutrition and infection . These effects are reversed by short-term nutritional support . Strategic nutritional intervention should thus be considered in management , especially in malnourished patients BACKGROUND Stunted children with cystic fibrosis ( CF ) have less net protein anabolism than do children without CF , and the result is retarded growth in the CF patients . It is not known whether protein intake above that recommended by the Cystic Fibrosis Foundation would further stimulate whole-body protein synthesis . OBJECTIVE We studied the effects of 3 amounts of protein intake on whole-body protein synthesis and breakdown by using isotopic infusion of [1-(13)C]valine and [(15)N(2)]urea in children with stable CF who required tube feeding . DESIGN In 8 pediatric CF patients , we administered 3 r and omly allocated isocaloric diets with normal ( NP ) , intermediate ( IP ) , and high ( HP ) amounts of protein ( 1.5 , 3 , and 5 g . kg(-1 ) . d(-1 ) , respectively ) by continuous drip feeding during a 4-d period at 6-wk intervals . Each patient acted as his or her own control . On the fourth day of feeding , whole-body protein synthesis and breakdown were measured . RESULTS Protein synthesis was significantly higher in the HP group ( x + /- SEM : 1.78 + /- 0.07 micromol . kg(-1 ) . min(-1 ) ) than in the IP ( 1.57 + /- 0.08 micromol . kg(-1 ) . min(-1 ) ; P=0.001 ) and NP ( 1.37 + /- 0.07 micromol . kg(-1 ) . min(-1 ) ; P < 0.001 ) groups . There were no significant differences in protein breakdown . Net retention of nitrogen was significantly higher in the HP group ( 12.93 + /- 1.42 micromol . kg(-1 ) . min(-1 ) ) than in the IP ( 7.61 + /- 1.40 micromol . kg(-1 ) . min(-1 ) ; P=0.01 ) and HP ( 2.48 + /- 0.20 micromol . kg(-1 ) . min(-1 ) ; P < 0.001 ) groups . CONCLUSION In stunted children with CF requiring tube feeding , the highest stimulation of whole-body protein synthesis was achieved with a short-term dietary protein intake of 5 g . kg(-1 ) . d(-1 ) Survival in cystic fibrosis has improved significantly in the last 30 years , with major therapeutic goals of delaying the progressive loss of pulmonary function and maintaining normal growth . Dual-energy X-ray absorptiometry ( DEXA ) was performed in children with cystic fibrosis ( CF ) to assess both bone mineral density and body composition . We hypothesised that there would be an association between body composition and pulmonary function in children with CF . Fifty subjects with CF ( 28 males ) , mean age 12.7 years , participated in the study . Body composition was determined by DEXA . Body mass index ( BMI ) was calculated from the ratio of weight/height2 ( kg/m2 ) . Lung function was assessed by spirometry . Most patients ( 78 % ) had mild lung disease . The mean forced expired volume in 1 sec percent predicted ( FEV1 % predicted ) for the 50 patients was 79.2 % ( range , 24 - 117 % ) . There was a strong association between FEV1 % predicted and BMI ( R=0.59 , P=0.0001 ) . Fat-free mass had positive association with pulmonary function tests ( R=0.30 , P=0.03 ) . Although fat mass showed a positive correlation with pulmonary function , this association did not reach statistical significance . In our group of children with CF and mild lung disease , pulmonary function was more strongly associated with BMI than with fat and fat-free mass High fat containing diets lower VCO(2)in patients with impaired pulmonary function fed at a high level of energy intake . We tested the effect of a high fat enteral nutrition on VCO(2 ) and substrate oxidation in cystic fibrosis patients fed enterally 130 % RDA . VCO(2 ) and substrate oxidation were studied in a group of eight 6 - 19 year old patients while receiving for 1 month and in a r and om order isocaloric ( 1000 kcal/m(2 ) ) , isonitrogenous enteral diet with a normal fat and a high fat content ( 40 % and 67 % of non-protein energy intake ) . Substrate oxidation and net balance were estimated using indirect calorimetry at the end of each study period . Overnight high fat enteral infusion result ed in no significant change in VCO(2 ) and VO(2)but lowered RQ ( 0.84 + /- 0.01 vs 0.88 + /- 0.01 , P= 0.02 ) and non-protein RQ ( 0.83 + /- 0.01 vs 0.88 + /- 0.01 ) . In spite of a higher glucose oxidation rate ( 8.1 + /- 0.5 vs 6.3 + /- 0.5 g. h(-1 ) , P= 0.04 ) , glucose net balance was significantly higher during normal fat formula administration ( + 2.5 + /- 0.8 v -0.3 7plusmn ; 0.7 g/h , P < 0.05 ) . The present study failed to show any benefit of a high fat diet on VCO(2)in non oxygenodependant cystic fibrosis children and adolescents fed slightly above RAD . Normal fat enteral formula led to higher glycogen repletion OBJECTIVE To determine whether differences in tolerance and absorption of fat and nitrogen exist between a semi-elemental nutritional formula without enzyme replacement and a nonelemental formula with enzyme replacement . STUDY DESIGN Sixteen patients ( eight girls and eight boys ) with cystic fibrosis , 4 to 20 years of age ( 12+/-1.3 , mean + /- SEM ) , who were pancreatic insufficient completed two 6-day regimens of nocturnal continuous enteral feedings offered in r and om order . Forty-four percent of the total daily energy was consumed as enteral tube feedings , and the remaining oral dietary intake remained constant throughout the study . Seventy-two-hour fecal collection s from each study period were analyzed for total fat , long-chain fatty acids ( LCFAs ) , medium-chain fatty acids ( MCFAs ) , and nitrogen . RESULTS Fat absorption was 80.2%+/-2.9 % and 82.3%+/-3.1 % ( p = 0.58 ) for the semi-elemental and nonelemental formulas , respectively . Similarly , the coefficient of absorption of LCFAs was 69.5%+/-4.5 % and 79.6%+/-3.4 % ( p = 0.30 ) for the semi-elemental and nonelemental formulas . Malabsorption of MCFAs contributed minimally to total fat malabsorption . There was no difference between formulas for MCFA or for nitrogen absorption , 83.7%+/-1.9 % and 87.4%+/-1.4 % , p = 0.48 . All patients tolerated all feedings , and weight gained was 1.8+/-0.3 kg with no difference in weight gain between the trials . CONCLUSION A nonelemental formula , with enzyme replacement , is absorbed as well as a predigested formula in patients with CF who are pancreatic insufficient BACKGROUND There is currently a lack of clinical data on fibre requirements in UK children . Subsequently , the ideal fibre profile for enteral formulae design ed to meet the requirements of older children is unknown . The present study aim ed to investigate the effect of fibre supplementation on gastrointestinal function of children aged 7 - 12 years ( or weight 21 - 45 kg ) receiving an age-specific high-energy enteral feed . METHODS In this double-blind r and omised crossover study , 25 home enterally tube-fed children with a range of medical conditions ( including cystic fibrosis , neurological conditions , liver transplant and bone marrow transplant ) were given a 1.5 kcal mL(-1 ) formula with or without added dietary fibre ( 1.13 g per 100 mL ) . Each formula was taken for 6 weeks , followed by 6 months on the second r and omly assigned formula . Anthropometry , blood biochemistry , stool characteristics , tolerance and oral dietary intake were assessed . RESULTS Despite a higher median fibre intake on the fibre-containing formula ( 84 % versus 26 % of recommended intake ; P = 0.003 ) , most children did not meet existing international recommendations for fibre as a result of small feed volumes ( median 800 mL day(-1 ) ; 9 g fibre day(-1 ) ) . There was some evidence of reduced constipation , laxative reliance and abdominal pain on the fibre-containing formula . CONCLUSIONS Given the poor fibre intakes and absence of adverse effects , the use of fibre-containing formulae should become st and ard practice for the majority of children on enteral feeds . Larger trials in children are required to further evaluate the effect of amount and blend of fibre in enteral formulae for older children . However , it is likely that current formulae require higher levels of fibre This study examined whether the increase in CO2 production ( VCO2 ) and ventilatory dem and s by carbohydrate loading with different formulas during nighttime enteral feedings could be detrimental in young adult cystic fibrosis patients with moderate to advanced lung disease . Ten patients age 17 to 24 ( mean 21.4 years ) received 1000 kcal/M2 of a low ( Pulmocare ) , medium ( Ensure Plus ) , and high ( Vivonex HN ) carbohydrate formula in r and om order . Eight patients had severe , and two moderate obstructive pulmonary disease ; nine used nighttime oxygen therapy . Basal energy expenditure ( BEE ) without feedings averaged 120 % of that predicted by the Harris-Benedict equation . The metabolic expenditure by indirect calorimetry during nighttime feedings was 25 to 36 % greater than the BEE . Oxygen consumption ( VO2 ) increased 21 to 27 % during nighttime feedings with no difference between formulas . VCO2 increased 29 % for Pulmocare , 46 % with Ensure Plus , and 53 % with Vivonex HN . The increase in VCO2 with Pulmocare was significantly less than Ensure Plus ( p less than 0.05 ) and Vivonex HN ( p less than 0.005 ) . The respiratory quotient ( RQ ) ( VCO2-/VO2 ) for Pulmocare ( 0.88 ) was the same as the BEE , but increased with Ensure Plus ( 1.00 ) , and Vivonex HN ( 1.08 ) . The 41 % increase in minute ventilation with Vivonex HN was greater than the 25 to 28 % increase observed for Pulmocare and Ensure Plus ( p less than 0.05 ) . Transcutaneous oxygen saturation fell no more than 2 % with all formulas . PCO2 changed + /- 5 torr during enteral feedings with similar changes in any patient with all formulas . ( ABSTRACT TRUNCATED AT 250 WORDS Background Patients with cystic fibrosis who have steatorrhea frequently are underweight and have essential fatty acid ( EFA ) depletion , which is associated with a poor clinical course . It has been stated that poor EFA status is difficult to correct in patients with cystic fibrosis , and an impaired EFA metabolism with reduced synthesis of long-chain polyunsaturated fatty acids has been proposed . In this study , the effects of an oral energy supplement rich in linoleic acid were investigated in patients with cystic fibrosis who had a body weight below 95 % of normal for height . Methods Thirty-six patients ( 16 girls ) more than 4 years of age were r and omized either to a control group ( n = 20 , age 13.3 ± 3.8 years , mean ± SD ) receiving intensive dietary counseling only , or an intervention group ( n = 16 , age , 10.4 ± 4.3 years ) treated for 3 months with dietary counseling plus 628 ± 254 mL ( = kcal ) per day of an energy supplement rich in fat ( 31 % of energy ) and linoleic acid ( 16 % of energy ) . Results In contrast to Output:	Supplemental enteral tube feeding is widely used throughout the world to improve nutritional status in people with cystic fibrosis . The methods mostly used , nasogastric or gastrostomy feeding , are expensive and may have a negative effect on self-esteem and body image .
MS22556	*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 AIM Some studies recently reported a favourable effect for cis-9 , trans-11 conjugated linoleic acid ( CLA ) on plasma lipoprotein profile of healthy subjects . Aim of this crossover intervention study was to evaluate the influence of a short-term dietary intake of a cheese derived from sheep 's milk naturally rich in CLA on several atherosclerotic biomarkers , in comparison with a commercially available cheese . METHODS AND RESULTS Ten subjects ( 6 F ; 4 M ) with a median age of 51.5 followed for 10 weeks a diet containing 200 g/week of cheese naturally rich in CLA ( intervention period ) and for the same period a diet containing a commercially available cheese of the same quantity ( placebo period ) . Consumption of the dairy product naturally rich in cis-9 , trans-11 CLA determined a significant ( p<0.05 ) reduction in inflammatory parameters such as interleukin-6 ( pre : 8.08+/-1.57 vs. post : 4.58+/-0.94 pg/mL ) , interleukin-8 ( pre : 45.02+/-5.82 vs. post : 28.59+/-2.64 pg/mL ) , and tumour necrosis factor-alpha ( pre : 53.58+/-25.67 vs. post : 32.09+/-17.42 pg/mL ) whereas no significant differences in the placebo period were observed . With regard to haemorheological parameters , the test period significantly ameliorated erythrocytes ' filtration rate ( pre : 7.61+/-0.71 % vs. post : 9.12+/-0.97 % ; p=0.03 ) with respect to the placebo period . Moreover , a reduction in the extent of platelet aggregation , induced by arachidonic acid [ pre : 87.8+/-1.76 % vs. post : 77.7+/-3.56 % ; p=0.04 ] was observed during the test period in comparison with the placebo period . CONCLUSIONS Dietary short-term intake of the tested dairy product naturally rich in cis-9 , trans-11 CLA appeared to cause favourable biochemical changes of atherosclerotic markers BACKGROUND AND AIMS Epidemiological studies have demonstrated an association between high-polyphenol intake and reduced incidence of atherosclerosis . The healthy effects of cocoa-polyphenols may be due to their antioxidant and anti-inflammatory actions , although the exact mechanisms are unknown and depend on the matrix in which cocoa-polyphenols are delivered . Nuclear factor κB ( NF-κB ) is a key molecule in the pathophysiology of atherosclerosis involved in the regulation of adhesion molecules(AM ) and cytokine expression and its activation is the first step in triggering the inflammatory process . The aim of this study was to evaluate the effect of acute cocoa consumption in different matrices related to the bioavailability of cocoa-polyphenols in NF-κB activation and the expression of AM . METHODS AND RESULTS Eighteen healthy volunteers r and omly received 3 interventions : 40 g of cocoa powder with milk ( CM ) , with water ( CW ) , and only milk ( M ) . NF-κB activation in leukocytes and AM ( sICAM , sVCAM , E-selectin ) were measured before and 6h after each intervention . Consumption of CW significantly decreased NF-κB activation compared to baseline and to CM ( P < 0.05 , both ) , did not change after CM intervention , and significantly increased after M intervention ( P = 0.014 ) . sICAM-1 concentrations significantly decreased after 6h of CW and CM interventions ( P ≤ 0.026 ; both ) and E-selectin only decreased after CW intervention ( P = 0.028 ) . No significant changes were observed in sVCAM-1 concentrations . CONCLUSIONS The anti-inflammatory effect of cocoa intake may depend on the bioavailability of bioactive compounds and may be mediated at least in part by the modulation of NF-κB activation and downstream molecules reinforcing the link between cocoa intake and health BACKGROUND & AIMS The study examined the value of n-3 LC-PUFA-enriched yogurt as means of improving cardiovascular health . DESIGN Fifty three mildly hypertriacylglycerolemic subjects ( TAG ≥ 1.7 mmol/L ) participated in a r and omized , placebo-controlled , double-blind , parallel design ed study . The subjects consumed 1 ) control yoghurt ; 2 ) yoghurt enriched with 0.8 g n-3 LC-PUFA/d ; or 3 ) yoghurt enriched with 3 g n-3 LC-PUFA/d for a period of 10 wks . Blood sample s were taken at the beginning and the end of the study period . RESULTS Following daily intake of 3 g n-3 LC-PUFA for 10 weeks , n-3 LC-PUFA levels increased significantly in plasma and red blood cells ( RBC ) with concomitant increase in the EPA-derived mediators ( PGE₃ , 12- , 15- , 18-HEPE ) in plasma whilst cardiovascular risk factors such as HDL , TAG , AA/EPA ratio , and n-3 index were improved ( P < 0.05 ) ; the decrease of TAG and increase in HDL were associated with the CD36 genotype . CONCLUSION The observed increase of n-3 LC-PUFA in RBC and plasma lipids due to intake of n-3 LC-PUFA enriched yoghurt result ed in a reduction of cardiovascular risk factors and inflammatory mediators showing that daily consumption of n-3 PUFA enriched yoghurt can be an effective way of supplementing the daily diet and improving cardiovascular health Intake of conjugated linoleic acid ( CLA ) has been demonstrated to beneficially affect risk markers of atherosclerosis and diabetes in rats . CLA is naturally found in milk fat , especially from cows fed a diet high in oleic acid , and increased CLA intake can occur concomitantly with increased milk fat intake . Our objective was to investigate the effect of CLA as part of a diet rich in butter as a source of milk fat on risk markers of atherosclerosis , inflammation , diabetes type II , and lipid peroxidation . A total of 38 healthy young men were given a diet with 115 g/d of CLA-rich fat ( 5.5 g/d CLA oil , a mixture of 39.4 % cis9 , trans11 and 38.5 % trans10 , cis12 ) or of control fat with a low content of CLA in a 5-wk double-blind , r and omized , parallel intervention study . We collected blood and urine before and after the intervention . The fatty acid composition of plasma triacylglycerol , cholesterol esters , and phospholipids reflected that of the intervention diets . The CLA diet result ed in increased lipid peroxidation measured as an 83 % higher 8-iso-prostagl and in F2alpha concentration compared with the control , P < 0.0001 . We observed no other significant differences in the effect of the interventions diets . In conclusion , when given as part of a diet rich in butter , a mixture of CLA isomers increased lipid peroxidation but did not affect risk markers of cardiovascular disease , inflammation , or fasting insulin and glucose concentrations BACKGROUND Epidemiologic studies have suggested that flavonoid intake plays a critical role in the prevention of coronary heart disease . Because atherosclerosis is considered a low- grade inflammatory disease , some feeding trials have analyzed the effects of cocoa ( an important source of flavonoids ) on inflammatory biomarkers , but the results have been controversial . OBJECTIVE The objective was to evaluate the effects of chronic cocoa consumption on cellular and serum biomarkers related to atherosclerosis in high-risk patients . DESIGN Forty-two high-risk volunteers ( 19 men and 23 women ; mean + /- SD age : 69.7 + /- 11.5 y ) were included in a r and omized crossover feeding trial . All subjects received 40 g cocoa powder with 500 mL skim milk/d ( C+M ) or only 500 mL skim milk/d ( M ) for 4 wk . Before and after each intervention period , cellular and serum inflammatory biomarkers related to atherosclerosis were evaluated . RESULTS Adherence to the dietary protocol was excellent . No significant changes in the expression of adhesion molecules on T lymphocyte surfaces were found between the C+M and M groups . However , in monocytes , the expression of VLA-4 , CD40 , and CD36 was significantly lower ( P = 0.005 , 0.028 , and 0.001 , respectively ) after C+M intake than after M intake . In addition , serum concentrations of the soluble endothelium-derived adhesion molecules P-selectin and intercellular adhesion molecule-1 were significantly lower ( both P = 0.007 ) after C+M intake than after M intake . CONCLUSIONS These results suggest that the intake of cocoa polyphenols may modulate inflammatory mediators in patients at high risk of cardiovascular disease . These antiinflammatory effects may contribute to the overall benefits of cocoa consumption against atherosclerosis . This trial was registered in the Current Controlled Trials at London , International St and ard R and omized Controlled Trial Number , at controlled-trials.com as IS RCT N75176807 BACKGROUND We recently showed that calcitriol increases oxidative and inflammatory stress ; moreover , inhibition of calcitriol with high-calcium diets decreased both adipose tissue and systemic oxidative and inflammatory stress in obese mice , whereas dairy exerted a greater effect . However , these findings may be confounded by concomitant changes in adiposity . OBJECTIVE The objective of this study was to evaluate the acute effects of a dairy-rich diet on oxidative and inflammatory stress in overweight and obese subjects in the absence of adiposity changes . DESIGN Twenty subjects ( 10 obese , 10 overweight ) participated in a blinded , r and omized , crossover study of dairy- compared with soy-supplemented eucaloric diets . Two 28-d dietary periods were separated by a 28-d washout period . Inflammatory and oxidative stress biomarkers were measured on days 0 , 7 , and 28 of each dietary period . RESULTS The dairy-supplemented diet result ed in significant suppression of oxidative stress ( plasma malondialdehyde , 22 % ; 8-isoprostane-F(2alpha ) , 12 % ; P < 0.0005 ) and lower inflammatory markers ( tumor necrosis factor-alpha , 15 % , P < 0.002 ; interleukin-6 , 13 % , P < 0.01 ; monocyte chemoattractant protein-1 , 10 % , P < 0.0006 ) and increased adiponectin ( 20 % , P < 0.002 ) , whereas the soy exerted no significant effect . These effects were evident by day 7 of treatment and increased in magnitude at the end of the 28-d treatment periods . There were no significant differences in response to treatment between overweight and obese subjects for any variable studied . CONCLUSION An increase in dairy food intake produces significant and substantial suppression of the oxidative and inflammatory stress associated with overweight and obesity . This trial was registered at clinical trials.gov as NCT00686426 n-3 long-chain PUFA ( n-3 LC-PUFA ) may improve cardiovascular and inflammatory diseases . The effects of n-3 LC-PUFA-supplemented dairy products on inflammation and immunological parameters , biomarkers of oxidative stress , serum lipids , and on disease activity were determined in patients with rheumatoid arthritis ( RA ) . Forty-five subjects ( forty-three females and two males ) were r and omly divided into two groups in a double-blind , placebo-controlled cross-over study . Both groups received placebo or verum products consecutively for 3 months with a 2-month washout phase between the two periods . Blood sample s were taken at the beginning and at the end of each period . The dairy products generally improved serum lipids by increasing HDL and lowering lipoprotein a. The n-3 LC-PUFA supplements act to lower TAG . Additionally , a decreased lipopolysaccharide-stimulated cylo-oxygenase-2 expression was found in patients who had consumed the enriched dairy products . The majority of the CD analysed were not influenced , although n-3 LC-PUFA did suppress the immune response as lymphocytes and monocytes were found to be significantly decreased . The n-3 LC-PUFA did not increase the biomarkers of oxidative stress such as 8-iso-PGF(2alpha ) and 15-keto-dihydro PGF(2alpha ) , and DNA damage like 7,8-dihydro-8-oxo-2'-deoxyguanosine . The long-term consumption of dairy products ( 2 x 12 weeks ) diminished the excretion of hydroxypyridinium Output:	When the subjects were stratified according to their health status , the IS was strongly indicative of an anti-inflammatory activity in subjects with metabolic disorders and of a pro-inflammatory activity in subjects allergic to bovine milk .
MS22557	*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 determine differences in interproximal plaque mass and fluoride retention with different modes of toothbrushing and flossing . MATERIAL S AND METHODS Forty-seven subjects in good health used four treatments in a four-period , r and omized , crossover design : 1 ) manual brushing only ; 2 ) manual brushing and daily flossing ; 3 ) electric brushing using a rotational oscillation toothbrush ; and 4 ) electric brushing using a sonic toothbrush . Subjects used a st and ard sodium fluoride dentifrice during the eight-day experimental periods and a fluoride-free dentifrice during the seven-day washout periods between treatments . Interproximal plaque sample s were taken on Day 1 and on Day 8 , weighed , and analyzed for fluoride content . RESULTS The amount of interproximal plaque was lowest with sonic brushing , which left 43 - 65 % less plaque than all other treatments . Manual brushing and flossing yielded less plaque than manual brushing alone and rotational oscillation brushing . Differences were statistically significant ( p < 0.05 ) for treatment ; there was no time effect on plaque mass . For fluoride retention , at Day 1 sonic brushing gave at least 54 % more fluoride in the interproximal plaque than all other treatments , which was significant . All treatments demonstrated a significant increase in fluoride concentration with time except manual brushing and flossing , which showed a significant decrease . At Day 8 , the fluoride concentration was significantly higher for sonic brushing than for manual brushing or rotational oscillation brushing by over 40 % , and all treatments exhibited significantly greater fluoride than the manual brushing and flossing combination . CONCLUSION The mode of toothbrushing may impact the amount of plaque retained interproximally and its fluoride concentration A clinical trial was conducted to evaluate the effects of a sanguinaria-zinc chloride dentifrice on the prevention of plaque formation and gingivitis . A total of 59 young adults , 18 to 30 years of age , either performed supervised brushing with a 0.075 % sanguinaria-0.05 % zinc chloride dentifrice , a 0.24 % sodium fluoride dentifrice , or rinsed daily with a 0.05 % NaF solution . Clinical evaluations for plaque and gingivitis were performed after 7 , 14 , and 21 days of the test regimen . After 21 days , all subjects resumed twice daily supervised brushing and flossing and post-test evaluations were conducted after two weeks . The results showed that after 7 , 14 , and 21 days both groups using dentifrices had significantly less plaque and gingivitis than the group using the rinse , and there were no significant differences between the two groups using either the sanguinaria-ZnCl2 or the NaF dentifrices OBJECTIVE To evaluate the safety and efficacy of a newly developed automated flossing device ( AF ) . METHODOLOGY Subjects were recruited from a university campus via announcements , and were r and omly assigned to a control ( C ) , manual ( M ) , or automated ( A ) group . Subjects brushed twice a day and treatment groups used their respective floss daily . The safety assessment ( SA ) , plaque index ( PI ) , and gingival index ( GI ) were measured at days one , 15 , and 30 . A pre- and post-intervention PI was measured at days 15 and 30 . RESULTS The majority of subjects ( n=76 ) were students , mean age + /- SD of 23.3 + /- 5.2 years . Based on one-way analysis of covariance , C had a higher mean PI score than A at days 15 ( p = 0.019 ) and 30 ( p < 0.001 ) , and M had a higher mean PI score than A at day 30 ( p = 0.022 ) . The C had a higher mean GI score than A at day 30 ( p = 0.034 ) . The SA included trauma associated with improper use of the AF for two subjects . CONCLUSION At four weeks , the AF removed more interproximal plaque than M , and there was less interdental inflammation compared to brushing alone . The AF is safe and effective when used properly , and demonstrates great promise as an alternative to manual floss The purpose of the present study was to compare in untreated patients suffering from moderate to severe periodontitis the efficacy of dental floss ( DF ) and interdental brushes ( IDB ) in the reduction of plaque , gingival inflammation , and probing depth in a 6-week period prior to subgingival debridement . Twenty-six patients ( 12 female , 14 male ; mean age 37.4 years ; range 27 to 72 years ) were instructed to use DF for one side of the dentition and IDB for the other side as an adjunct to the daily toothbrushing for 6 weeks . Oral hygiene instructions for toothbrushing and the use of the two devices were given at baseline and at week 3 . Measurements were carried out at baseline and at 6 weeks including plaque scores , probing depth , and 2 bleeding scores ( periodontal pocket bleeding index and angulated bleeding index ) . With the IDB , the approximal plaque score at baseline of 3.09 reduced to 2.15 at 6 weeks and with DF from 3.10 to 2.47 , respectively . IDB proved to remove significantly more plaque than DF . Baseline probing depth of 5.84 mm for IDB sites and 5.59 mm for DF sites was reduced to 5.01 mm at 6 weeks for both regimens . Analysis showed that the use of IDB result ed in a greater pocket reduction . Both bleeding indices were slightly reduced with IDB and DF , but no differences between devices were found . In relation to patient acceptance , more problems were observed with DF , and IDB were felt to be more efficacious . In conclusion , the results of the present study indicate that in combination with a manual toothbrush , the use of interdental brushes is more effective in removal of plaque and results in a larger reduction of probing depth than the use of dental floss . Although the differences were small , they indicate , in combination with patient preferences , that interdental brushes are to be considered preferable to floss for interdental plaque removal in patients suffering from moderate to severe periodontitis OBJECTIVE The study was conducted to compare the performance of three interdental products to dental floss in the control and removal of plaque , and in the reduction of gingivitis . METHODOLOGY One-hundred and twenty subjects were screened for the presence of interproximal sites of a size suitable for a GUMO Go-Betweens cleaner , and for being in compliance with inclusion and exclusion criteria . They were then assessed with the Plaque , Gingivitis , and Eastman Interdental Bleeding Indices ( EIBI ) at baseline , given a prophylaxis , r and omly assigned to one of four products ( Glide dental floss , Butler flossers , GUM Go-Betweens cleaners , and GUM Soft-Picks cleaners ) , and given product use instructions . Subjects returned at three weeks for a compliance review and at six weeks for a final visit . Plaque was assessed at the final visit before and after using the assigned products . Plaque , gingivitis , and bleeding scores were evaluated by analysis of covariance using the baseline measurements as the covariate . RESULTS All four interdental products significantly reduced interdental plaque from baseline to before-use at the final visit ( after six weeks ) employing baseline plaque as a covariate . Reductions were 16 % to 24 % . Similarly , use of the products at the final visit result ed in 26 % to 31 % reductions in plaque with the before-use plaque as a covariate . Interdental gingivitis scores showed a reduction both lingually and buccally , with reductions ranging from 27 % to 36 % for the former and 34 % to 53 % for the latter ( baseline was the covariate ) . No statistical differences were found between the products on the lingual interdental sites . The Go-Betweens cleaners showed a statistically greater reduction in the Gingival Index score buccally than the other three products . No differences were noted among the products for the EIBI . CONCLUSION In this study , dental floss , the recognized " gold st and ard " for gingivitis reduction , was matched in performance by flossers and an interdental cleaner with small elastomeric fingers , and surpassed by an interdental brush . All products performed comparably for plaque reduction and removal AIM The purpose of the present study was to compare 2 indices , i.e. , the Eastman interdental bleeding ( EIB ) index and the bleeding on marginal probing ( BOMP ) index . The comparison was made ( a ) in terms of the degree of bleeding provoked and the relationship with plaque in natural gingivitis and ( b ) for the ability of these 2 methods to detect differences between the development of experimental gingivitis in a control group and a group in which the development of gingival inflammation was suppressed by treatment . For the present studies , subjects were selected without interdental recession of the gingival tissues . METHODS EXPERIMENT 1 : In this experiment , 43 subjects having established moderate gingivitis were assessed using a r and om splitmouth design ( 1st and 3rd/2nd and 4th quadrant ) . Plaque was scored on all approximal sites after which the BOMP index was assessed in one half of the mouth and the EIB index in the other . RESULTS EXPERIMENT 1 : The BOMP index showed a bleeding score of 84 % and the EIB index of 87 % . The significant correlation between plaque and gingival bleeding for the BOMP index ( 0.55 ) was higher than for the EIB index ( 0.44 ) . METHODS EXPERIMENT 2 : For this experiment , 25 subjects participated in an experimental gingivitis trial of the lower jaw . At baseline , first the BOMP index and immediately thereafter the EIB index were assessed at all approximal sites . Experimental gingivitis ( EG ) was carried out in one r and omly assigned quadrant and as a treatment modality only floss was used in the other ( FL ) . RESULTS EXPERIMENT 2 : In the EG quadrant , the BOMP index increased to 69 % and the EIB index to 73 % . Both indices showed a significant correlation with plaque ; 0.60 and 0.64 respectively . In the FL quadrant , the BOMP index increased to 38 % and the EIB index to 30 % . No significant correlation between both gingivitis indices and the amount of plaque was present in the FL quadrant . CONCLUSION The ability of the BOMP index and the EIB index to assess the level gingival inflammation appears to be comparable Overemphasis on hypothesis testing-- and the use of P values to dichotomise significant or non-significant results --has detracted from more useful approaches to interpreting study results , such as estimation and confidence intervals . In medical studies investigators are usually interested in determining the size of difference of a measured outcome between groups , rather than a simple indication of whether or not it is statistically significant . Confidence intervals present a range of values , on the basis of the sample data , in which the population value for such a difference may lie . Some methods of calculating confidence intervals for means and differences between means are given , with similar information for proportions . The paper also gives suggestions for graphical display . Confidence intervals , if appropriate to the type of study , should be used for major findings in both the main text of a paper and its abstract BACKGROUND Manual floss is often difficult to use , particularly in hard to reach posterior teeth . Many prefer automated flossers because of their ease of use . The aim of the present study was to compare the effectiveness of an automated flosser to manual floss for anterior , premolar , and molar teeth using the plaque index ( PI ) and gingival ( GI ) index . METHODS A 10-week , two-treatment period , crossover design was used . The subjects were r and omly assigned to control ( C ) , manual ( M ) , or automated ( A ) groups . The PI and GI were measured interdentally at baseline and days 15 and 30 . Treatment subjects were assigned to the opposite group at the second baseline visit after a 2-week washout period . Subjects brushed twice a day . Treatment subjects used their respective floss once per day . Subjects refrained from oral hygiene 24 hours before study visits . The PI was measured pre- and postintervention on days 15 and 30 . Mixed-effect analysis of covariance crossover models were used to test group effects at days 15 and 30 from both periods with the corresponding mean preintervention and baseline score as covariates for PI and GI , respectively . Within-subject treatment comparisons were made , and carryover effects were evaluated . RESULTS The majority of subjects ( N = 102 ) were students ( mean age , 23.3 + /- 5.0 [ SD ] years ) with minimal gingivitis at baseline . At days 15 and 30 , the M group had more plaque than the A group for all regions ( P < or = 0.008 ) , and the C group had more plaque than the A ( P < 0.001 ) and M groups ( P < or = 0.021 ) for all regions . No regional treatment effect was observed for the GI . Within-subject analyses were more favorable for the A group than the M group . No significant carryover effect was observed . CONCLUSIONS The automated flossing device removed significantly more interproximal plaque in molar , premolar , and anterior teeth compared to manual floss at days 15 and 30 . There was no significant difference in interdental inflammation between groups OBJECTIVE The objective of this examiner-blind clinical study was to investigate the efficacy of three oral hygiene regimens for the control of gingivitis and supragingival plaque . METHODOLOGY Following a baseline examination for gingivitis and suprag Output:	A greater part of the studies did not show a benefit for floss on plaque and clinical parameters of gingivitis . In light of the results of this comprehensive literature search and critical analysis , it is concluded that a routine instruction to use floss is not supported by scientific evidence
MS22558	*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 r and omized behavioral trial examined whether youth living with HIV ( YLH ) receiving cell-phone support with study funded phone plans , demonstrated improved adherence and viral control during the 24 week intervention and 24 weeks post-intervention compared to controls . Monday through Friday phone calls confirmed medications were taken , provided problem-solving support , and referred to services to address adherence barriers . Of 37 participants ( ages 15–24 ) , 62 % were male and 70 % were African American . Self-reported adherence was significantly higher in the intervention group compared to the control at 24 and 48 weeks for the past month ( P = 0.007 ) and log 10 HIV VL was significantly lower at both 24 weeks ( 2.82 versus 4.52 P = 0.002 ) and 48 weeks ( 3.23 versus 4.23 P = 0.043 ) . Adherence and viral load showed medium to large effect sizes across the 48 week study . This is the first study to demonstrate sustained clinical ly significant reductions in HIV VL using youth friendly technology . ResumenEste ensayo de comportamiento aleatorio examinó si los jóvenes que viven con el VIH ( YLH ) reciben apoyo por celular con el estudio financiado de teléfono , se demostró un mejor cumplimiento y control viral durante la intervención de 24 semanas y 24 semanas después de la intervención en comparación con los controles . De Lunes a Viernes las llamadas telefónicas confirmaron los medicamentos , apoyaron la resolución de problemas , y se refirió a los servicios para hacer frente a las barreras de adherencia . De los 37 participantes ( siglos 15–24 ) , el 62 % eran hombres y el 70 % eran afroamericanos . Adherencia auto-reportada fue significativamente mayor en el grupo de intervención en comparación con el control a las 24 y 48 semanas del mes pasado ( P = 0.007 ) y el log 10 VL VIH fue significativamente menor en ambos 24 semanas ( 2.82 versus 4.52 P = 0.002 ) y 48 semanas ( 3.23 versus 4.23 P = 0.043 ) . La adhesión y la carga viral mostraron medianas y gr and es tamaños del efecto en todo el estudio de 48 semanas . Este es el primer estudio que demuestra descensos importantes de la VL VIH utiliz and o tecnología amigable para la juventud HIV-positive adolescents and young adults often experience suboptimal medication adherence , yet few interventions to improve adherence in this group have shown evidence of efficacy . We conducted a r and omized trial of a two-way , personalized daily text messaging intervention to improve adherence to antiretroviral therapy ( ART ) among N = 105 poorly adherent HIV-positive adolescents and young adults , ages 16–29 . Adherence to ART was assessed via self-reported visual analogue scale ( VAS ; 0–100 % ) at 3 and 6-months for mean adherence level and proportion ≥90 % adherent . The average effect estimate over the 6-month intervention period was significant for ≥90 % adherence ( OR = 2.12 , 95 % CI 1.01–4.45 , p < .05 ) and maintained at 12-months ( 6 months post-intervention ) . Satisfaction scores for the intervention were very high . These results suggest both feasibility and initial efficacy of this approach . Given study limitations , additional testing of this intervention as part of a larger clinical trial with objective and /or clinical outcome measures of adherence is warranted Social media technologies have become increasingly useful tools for research -based interventions . However , participants and social media users have expressed ethical concerns with these studies , such as risks and benefits of participation , as well as privacy , confidentiality , and informed consent issues . This study was design ed to follow up with and assess experiences and perceptions of ethics-related issues among a sample of 211 men who have sex with men who participated in the Harnessing Online Peer Education ( HOPE ) Peru study , a r and omized controlled HIV prevention intervention conducted in Peru . We found that after adjusting for age , highest educational attainment , race , sexual orientation , and prior HIV research experience , participants in the intervention group were more likely than those in the control group to have safe sex ( p = 0.0051 ) and get tested for HIV regularly ( p = 0.0051 ) . As a result of their participation , those in the intervention group benefited more positively than participants in the control group in improving HIV care ( p = 0.0077 ) and learning where to receive sexual health services ( p = 0.0021 ) . Participants in the intervention group expressed higher levels of comfort than those in the control group in joining and seeing other people in the Facebook group ( p = 0.039 ) , seeing other people ’s posts ( p = 0.038 ) and having other group members talk to them online ( p = 0.040 ) . We discuss the implication s of these results as they relate to social media-based HIV research & NA ; Patient engagement in care and adherence to medication are critical to achieving the full benefits of antiretroviral therapy ( ART ) among people with HIV infection . A r and omized controlled trial in Kenya , WelTelKenya1 , showed that an interactive mobile phone text‐messaging intervention can improve adherence and viral load suppression . We conducted a pilot study to adapt the WelTel intervention for HIV‐infected clients ( n = 25 ) at an HIV clinic in Vancouver , British Columbia . Between April and June 2012 , we recruited five participants from five groups : youth ( 14–24 years ) , mature ( ≥50 years ) , English as a second language , remote ( ≥3 hours travel time to clinic ) , and nonsuppressed ( CD4 + T cell count < 200 cells/mm3 and viral load ≥250 copies/mL on two consecutive occasions ) . Participants described the intervention as a useful way to communicate with health care providers , thus increasing the ability to access services , report side effects , and attend appointments Objective : To explore the effects of four types of short message service ( SMS ) plus real-time adherence monitoring on antiretroviral therapy ( ART ) adherence : daily reminders , weekly reminders , reminders triggered after a late or missed dose ( delivered to patients ) , and notifications triggered by sustained adherence lapses ( delivered to patient-nominated social supporters ) . Design : Pilot r and omized controlled trial . Methods : Sixty-three individuals initiating ART received a real-time adherence monitor and were r and omized ( 1 : 1 : 1 ) : ( 1 ) Scheduled SMS reminders ( daily for 1 month , weekly for 2 months ) , then SMS reminders triggered by a late or missed dose ( no monitoring signal within 2 h of expected dosing ) ; SMS notifications to social supporters for sustained adherence lapses ( no monitoring signal for > 48 h ) added after 3 months . ( 2 ) Triggered SMS reminders starting at enrolment ; SMS notifications to social supporters added after 3 months . ( 3 ) Control : No SMS . HIV RNA was determined at 9 months . Percentage adherence and adherence lapses were compared by linear generalized estimating equations and Poisson regression , respectively . Results : Median age was 31 years , 65 % were women , and median enrolment CD4 + cell count was 322 cells/&mgr;l 97 % took once daily tenofovir/emtricitabine/efavirenz . Compared to control , adherence was 11.1 % higher ( P = 0.04 ) and more than 48-h lapses were less frequent ( IRR 0.6 , P = 0.02 ) in the scheduled SMS arm . Adherence and more than 48-h lapses were similar in the triggered SMS arm and control . No differences in HIV RNA were seen . Conclusion : Scheduled SMS reminders improved ART in the context of real-time monitoring . Larger studies are needed to determine the impact of triggered reminders and role of social supporters in improving adherence Adherence to antiretroviral therapy ( ART ) represents one of the strongest predictors of progression to AIDS , yet it is difficult for most patients to sustain high levels of adherence . This study compares the efficacy of a personalized cell phone reminder system ( ARemind ) in enhancing adherence to ART versus a beeper . Twenty-three HIV-infected subjects on ART with self-reported adherence less than 85 % were r and omized to a cellular phone ( CP ) or beeper ( BP ) . CP subjects received personalized text messages daily ; in contrast , BP subjects received a reminder beep at the time of dosing . Interviews were scheduled at weeks 3 and 6 . Adherence to ART was measured by self-report ( SR , 7-day recall ) , pill count ( PC , past 30 days at baseline , then past 3 weeks ) , Medication Event Monitoring System ( MEMS ; cumulatively at 3 and 6 weeks ) , and via a composite adherence score constructed by combining MEMS , pill count , and self report . A mixed effects model adjusting for baseline adherence was used to compare adherence rates between the intervention groups at 3 and 6 weeks . Nineteen subjects completed all visits , 10 men and 9 females . The mean age was 42.7 ± 6.5 years , 37 % of subjects were Caucasian and 89 % acquired HIV heterosexually . The average adherence to ART was 79 % by SR and 65 % by PC at baseline in both arms ; over 6 weeks adherence increased and remained significantly higher in the ARemind group using multiple measures of adherence . A larger and longer prospect i ve study is needed to confirm these findings and to better underst and optimal reminder messages and user fatigue Background : HIV and AIDS are major public health problems in the world and Africa . In Cameroon , the HIV prevalence is 5.1 % . Cellphones have been found to be useful in the provision of modern health care services using short message services ( SMS ) . This study assessed the effectiveness of SMS in improving the adherence of people living with HIV and AIDS to their treatment and care in Cameroon . Methods : This intervention study used a r and omized controlled trial design . Ninety participants seeking treatment at the Nkwen Baptist Health Center were recruited between August and September 2011 using a purposive sampling method . They were r and omly allocated into the intervention and control groups , each containing 45 participants . In the intervention group , each participant received four SMSs per week at equal intervals for four weeks . The patients were investigated for adherence to ARVs by evaluating the number of times treatment and medication refill appointments were missed . Data were collected using an interviewer-administered question naire before and after intervention and analysed on STATA . Results : The baseline survey indicated that there were 55(61.1 % ) females and 35(38.9 % ) males aged 23 - 62 years ; the mean age was 38.77 ± 1.08 . Most participants were teachers [ 12 ( 13.3 % ) ] , farmers [ 11 ( 12.2 % ) ] , and businessmen [ 24 ( 26.7 % ) ] . Adherence to ARVs was 64.4 % in the intervention group and 44.2 % in the control group ( p = 0.05 ) . 2(4.4 % ) patients in the control group failed to respect their drug refill appointments while all the 45(100 % ) participants in the intervention group respected their drug refill appointments . 54.17 % of married people and 42.9 % of the participants with primary and secondary levels of education missed their treatment . Key reasons for missing treatment were late home coming ( 54 % ) , forgetfulness ( 22.5 % ) , and travelling out of station without medication ( 17.5 % ) . Other factors responsible for non-adherence included involvement in outdoor business ( 60.87 % ) , ARV stock out ( 37.8 % ) , and not belonging to a support group ( 10.23 % ) . Twenty eight ( 62.22 % ) subjects in the intervention group were able to take their treatment regularly and on time . Conclusion : SMS improved adherence to ARVs . Key constraints which affect adhere to ARV medication can be addressed using SMS Background Following male circumcision for HIV prevention , a high proportion of men fail to return for their scheduled seven-day post-operative visit . We evaluated the effect of short message service ( SMS ) text messages on attendance at this important visit . Methodology We enrolled 1200 participants > 18 years old in a two-arm , parallel , r and omized controlled trial at 12 sites in Nyanza province , Kenya . Participants received daily SMS text messages for seven days ( n = 600 ) or usual care ( n = 600 ) . The primary outcome was attendance at the scheduled seven-day post-operative visit . The primary analysis was by intention-to-treat . Principal Findings Of participants receiving SMS , 387/592 ( 65.4 % ) returned , compared to 356/596 ( 59.7 % ) in the control group ( relative risk [ RR ] = 1.09 , 95 % confidence interval [ CI ] 1.00–1.20 ; p = 0.04 ) . Men who paid more than US$ 1.25 to travel to clinic were at higher risk for failure to return compared to those who spent ≤US$1.25 ( adjusted relative risk [ aR Output:	Digital innovations were acceptable , feasible and generated impact . A trend towards the use of internet-based and combined ( internet and mobile ) innovations was noted .
MS22559	*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: Composite outcomes , in which multiple end points are combined , are frequently used as primary outcome measures in r and omized trials and are often associated with increased statistical efficiency . However , such measures may prove challenging for the interpretation of results . In this article , we examine the use of composite outcomes in major clinical trials , assess the arguments for and against them , and provide guidance on their application and reporting . To assess incidence and quality of reporting , we systematic ally review ed the use of composite end points in clinical trials in Annals of Internal Medicine , BMJ , Circulation , Clinical Infectious Diseases , Journal of the American College of Cardiology , JAMA , Lancet , New Engl and Journal of Medicine , and Stroke from 1997 through 2001 using a sensitive search strategy . We selected for review 167 original reports of r and omized trials ( with a total of 300 276 patients ) that included a composite primary outcome that incorporated all-cause mortality . Sixty-three trials ( 38 % ) were neutral both for the primary end point and the mortality component . Sixty trials ( 36 % ) reported significant results for the primary outcome measure but not for the mortality component . Only 6 trials ( 4 % ) were significant for the mortality component but not for the primary composite outcome , whereas 19 trials ( 11 % ) were significant for both . Twenty-two trials ( 13 % ) were inadequately reported . Our review suggests that reporting of composite outcomes is generally inadequate , implying that the results apply to the individual components of the composite outcome rather than only to the overall composite . Current guidelines for the undertaking and reporting of clinical trials could be revised to reflect the common use of composite outcomes in clinical trials BACKGROUND In the Action in Diabetes and Vascular Disease : Preterax and Diamicron Modified Release Controlled Evaluation ( ADVANCE ) factorial trial , the combination of perindopril and indapamide reduced mortality among patients with type 2 diabetes , but intensive glucose control , targeting a glycated hemoglobin level of less than 6.5 % , did not . We now report results of the 6-year post-trial follow-up . METHODS We invited surviving participants , who had previously been assigned to perindopril-indapamide or placebo and to intensive or st and ard glucose control ( with the glucose-control comparison extending for an additional 6 months ) , to participate in a post-trial follow-up evaluation . The primary end points were death from any cause and major macrovascular events . RESULTS The baseline characteristics were similar among the 11,140 patients who originally underwent r and omization and the 8494 patients who participated in the post-trial follow-up for a median of 5.9 years ( blood-pressure-lowering comparison ) or 5.4 years ( glucose-control comparison ) . Between-group differences in blood pressure and glycated hemoglobin levels during the trial were no longer evident by the first post-trial visit . The reductions in the risk of death from any cause and of death from cardiovascular causes that had been observed in the group receiving active blood-pressure-lowering treatment during the trial were attenuated but significant at the end of the post-trial follow-up ; the hazard ratios were 0.91 ( 95 % confidence interval [ CI ] , 0.84 to 0.99 ; P=0.03 ) and 0.88 ( 95 % CI , 0.77 to 0.99 ; P=0.04 ) , respectively . No differences were observed during follow-up in the risk of death from any cause or major macrovascular events between the intensive-glucose-control group and the st and ard-glucose-control group ; the hazard ratios were 1.00 ( 95 % CI , 0.92 to 1.08 ) and 1.00 ( 95 % CI , 0.92 to 1.08 ) , respectively . CONCLUSIONS The benefits with respect to mortality that had been observed among patients originally assigned to blood-pressure-lowering therapy were attenuated but still evident at the end of follow-up . There was no evidence that intensive glucose control during the trial led to long-term benefits with respect to mortality or macrovascular events . ( Funded by the National Health and Medical Research Council of Australia and others ; ADVANCE-ON Clinical Trials.gov number , NCT00949286 . ) Much of the controversy at the American Diabetes Association Scientific Sessions , held 6–10 June 2008 in San Francisco , California , pertained to questions raised about the benefits of intensive glycemic control by three large clinical studies : the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial , the Action in Diabetes and Vascular Disease ( ADVANCE ) trial , and the Veterans ’ Administration Diabetes Trial ( VADT ) . All three presented somewhat negative study results . David Goff ( Winston-Salem , NC ) discussed the ACCORD study design . The goal of ACCORD was to determine whether cardiovascular disease ( CVD ) event rates could be reduced by intensively treating three important risk factors ( hyperglycemia , dyslipidemia , and high blood pressure ) in a double 2 × 2 factorial design . For glycemia , the question of A1C < 6 vs. 7–7.9 % was addressed . Goff review ed previous studies that led to the decision to aim for the low A1C target . In the UK Prospect i ve Diabetes Study ( UKPDS ) , insulin and sulfonylurea treatment achieved a mean A1C level of 7 % , with 7.9 % in a control group . The 16 % CVD reduction just missed statistical significance . Metformin treatment in this study achieved a mean A1C level of 7.4 % with 8 % in a control group , associated with a significant 39 % CVD reduction . ( Goff did not mention that , compared with sulfonylureas alone , the other UKPDS metformin sub study showed that metformin with a sulfonylurea was associated with 96 , 60 , and 9 % increases in diabetes-related and all-cause mortality and in myocardial infa rct ion [ 1 ] . ) A nonsignificant CVD risk reduction of ∼50 % was seen in the Kumamoto study , while there was also a nonsignificant CVD risk increase of ∼50 % in the Veterans ’ Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes ( VACSDM ) ; both studies showed A1C 7.1 % in the treatment group and 9.3–9.4 % in the control group . Analysis of a number of observational studies OBJECTIVE The epidemic of type 2 diabetes ( T2DM ) threatens to become the major public health problem of this century . However , a comprehensive comparison of the long-term effects of medications to treat T2DM has not been conducted . GRADE , a pragmatic , unmasked clinical trial , aims to compare commonly used diabetes medications , when combined with metformin , on glycemia-lowering effectiveness and patient-centered outcomes . RESEARCH DESIGN AND METHODS GRADE was design ed with support from a U34 planning grant from the National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) . The consensus protocol was approved by NIDDK and the GRADE Research Group . Eligibility criteria for the 5,000 metformin-treated subjects include < 5 years ' diabetes duration , ≥30 years of age at time of diagnosis , and baseline hemoglobin A1c ( A1C ) of 6.8–8.5 % ( 51–69 mmol/mol ) . Medications representing four classes ( sulfonylureas , dipeptidyl peptidase 4 inhibitors , glucagon-like peptide 1 receptor agonists , and insulin ) will be r and omly assigned and added to metformin ( minimum – maximum 1,000–2,000 mg/day ) . The primary metabolic outcome is the time to primary failure defined as an A1C ≥7 % ( 53 mmol/mol ) , subsequently confirmed , over an anticipated mean observation period of 4.8 years ( range 4–7 years ) . Other long-term metabolic outcomes include the need for the addition of basal insulin after a confirmed A1C > 7.5 % ( 58 mmol/mol ) and , ultimately , the need to implement an intensive basal/bolus insulin regimen . The four drugs will also be compared with respect to selected microvascular complications , cardiovascular disease risk factors , adverse effects , tolerability , quality of life , and cost-effectiveness . CONCLUSIONS GRADE will compare the long-term effectiveness of major glycemia-lowering medications and provide guidance to clinicians about the most appropriate medications to treat T2DM . GRADE begins recruitment at 37 centers in the U.S. in 2013 BACKGROUND Improved blood-glucose control decreases the progression of diabetic microvascular disease , but the effect on macrovascular complications is unknown . There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation . We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a r and omised controlled trial . METHODS 3867 newly diagnosed patients with type 2 diabetes , median age 54 years ( IQR 48 - 60 years ) , who after 3 months ' diet treatment had a mean of two fasting plasma glucose ( FPG ) concentrations of 6.1 - 15.0 mmol/L were r and omly assigned intensive policy with a sulphonylurea ( chlorpropamide , glibenclamide , or glipizide ) or with insulin , or conventional policy with diet . The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group , the aim was the best achievable FPG with diet alone ; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment : any diabetes-related endpoint ( sudden death , death from hyperglycaemia or hypoglycaemia , fatal or non-fatal myocardial infa rct ion , angina , heart failure , stroke , renal failure , amputation [ of at least one digit ] , vitreous haemorrhage , retinopathy requiring photocoagulation , blindness in one eye , or cataract extraction ) ; diabetes-related death ( death from myocardial infa rct ion , stroke , peripheral vascular disease , renal disease , hyperglycaemia or hypoglycaemia , and sudden death ) ; all-cause mortality . Single clinical endpoints and surrogate sub clinical endpoints were also assessed . All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy . FINDINGS Over 10 years , haemoglobin A1c ( HbA1c ) was 7.0 % ( 6.2 - 8.2 ) in the intensive group compared with 7.9 % ( 6.9 - 8.8 ) in the conventional group -- an 11 % reduction . There was no difference in HbA1c among agents in the intensive group . Compared with the conventional group , the risk in the intensive group was 12 % lower ( 95 % CI 1 - 21 , p=0.029 ) for any diabetes-related endpoint ; 10 % lower ( -11 to 27 , p=0.34 ) for any diabetes-related death ; and 6 % lower ( -10 to 20 , p=0.44 ) for all-cause mortality . Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25 % risk reduction ( 7 - 40 , p=0.0099 ) in microvascular endpoints , including the need for retinal photocoagulation . There was no difference for any of the three aggregate endpoints between the three intensive agents ( chlorpropamide , glibenclamide , or insulin ) . Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis ( both p<0.0001 ) . The rates of major hypoglycaemic episodes per year were 0.7 % with conventional treatment , 1.0 % with chlorpropamide , 1.4 % with glibenclamide , and 1.8 % with insulin . Weight gain was significantly higher in the intensive group ( mean 2.9 kg ) than in the conventional group ( p<0.001 ) , and patients assigned insulin had a greater gain in weight ( 4.0 kg ) than those assigned chlorpropamide ( 2.6 kg ) or glibenclamide ( 1.7 kg ) . INTERPRETATION Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications , but not macrovascular disease , in patients with type 2 diabetes . ( ABSTRACT TRUNCATED Abstract Objective : To estimate the cost effectiveness of conventional versus intensive blood glucose control in patients with type 2 diabetes . Design : Incremental cost effectiveness analysis alongside r and omised controlled trial . Setting : 23 UK hospital clinic based study centres . Participants : 3867 patients with newly diagnosed type 2 diabetes ( mean age 53 years ) . Interventions : Conventional ( primarily diet ) glucose control policy versus intensive control policy with a sulphonylurea or insulin . Main outcome measures : Incremental cost per event-free year gained within the trial period . Results : Intensive glucose control increased trial treatment Output:	This evidence reported no significant impact of tight glycemic control on the risk of dialysis/transplantation/renal death , blindness , or neuropathy . Discordance exists between the research evidence and academic and clinical policy statements about the value of tight glycemic control to reduce micro- and macrovascular complications .
MS22560	*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 Tinnitus Research Consortium ( TRC ) issued a Request for Proposals in 2003 to develop a new tinnitus outcome measure that would : ( 1 ) be highly sensitive to treatment effects ( vali date d for " responsiveness " ) ; ( 2 ) address all major dimensions of tinnitus impact ; and ( 3 ) be vali date d for scaling the negative impact of tinnitus . A grant was received by M. Meikle to conduct the study . In that observational study , all of the TRC objectives were met , with the final 25-item Tinnitus Functional Index ( TFI ) containing eight subscales . The study was published in 2012 , and since then the TFI has received increasing international use and is being translated into at least 14 language s. The present study utilized data from a r and omized controlled trial ( RCT ) that involved testing the efficacy of " telephone tinnitus education " as intervention for bothersome tinnitus . These data were used to confirm results from the original TFI study . Overall , the TFI performed well in the RCT with Cohen 's d being 1.23 . There were large differences between the eight different subscales , ranging from a mean 13.2-point reduction ( for the Auditory subscale ) to a mean 26.7-point reduction ( for the Relaxation subscale ) . Comparison of TFI performance was made with the Tinnitus H and icap Inventory . All of the results confirmed sensitivity of the TFI along with its subscales . This article is part of a Special Issue entitled OBJECTIVE Using a r and omized group design , the efficacy of an outpatient cognitive-behavioral Tinnitus Coping Training ( TCT ) was compared to two minimal-contact ( MC ) interventions . METHODS TCT was conducted in a group format with 11 sessions ( total n=43 ) . One MC [ MC-E ( education ) , n=16 ] consisted of two group sessions in which education on tinnitus was presented and self-help strategies were introduced . The second MC [ MC-R ( relaxation ) , n=16 ] comprised four sessions . Besides education , music-supported relaxation was suggested as self-help strategy and audiotapes with relaxing music were provided . Furthermore , a waiting-list control group was installed ( WC , n=20 ) . Data were assessed at baseline ( pretherapy ) and at posttherapy period . Only TCT was additionally evaluated at a 6-month and a 12-month follow-up . Several outcome variables ( e.g. , awareness of tinnitus ) were recorded in a tinnitus diary . Tinnitus coping and disability due to tinnitus were assessed by question naires . Subjective ratings of improvement were also requested from the patients . Furthermore , inventories of psychopathology were given to the patients . RESULTS Findings reveal highly significant improvements in TCT in comparison to the control group ( WC ) . MC interventions do not differ significantly from each other , but are superior to WC in a few domains of outcome . Outcome in TCT is somewhat superior to combined MC interventions in two domains of data , but not regarding disability reduction . Effect sizes , nevertheless , indicate distinct differences in degree of improvement , with TCT achieving the best results . CONCLUSIONS A sequential scheme for the treatment of chronic tinnitus is discussed on the basis of cost-effectiveness considerations Many tinnitus sufferers believe that their tinnitus has an organic basis and thus seek medical rather than psychological treatments . Tinnitus has been found to be associated with negative appraisal , dysfunctional attention shift , and heightened psychophysiological arousal , so cognitive-behavioral interventions and biofeedback are commonly suggested as treatments . This study developed and investigated the efficacy of a biofeedback-based cognitive-behavioral treatment for tinnitus . In total , 130 tinnitus patients were r and omly assigned to an intervention or a wait-list control group . Treatment consisted of 12 sessions of a biofeedback-based behavioral intervention over a 3-month period . Patients in the wait-list group participated in the treatment after the intervention group had completed the treatment . Results showed clear improvements regarding tinnitus annoyance , diary ratings of loudness , and feelings of controllability . Furthermore , changes in coping cognitions as well as changes in depressive symptoms were found . Improvements were maintained over a 6-month follow-up period in which medium-to-large effect sizes were observed . The treatment developed and investigated in this study is well accepted and leads to clear and stable improvements . Through demonstration of psychophysiological interrelationships , the treatment enables patients to change their somatic illness perceptions to a more psychosomatic point of view For the first time , the therapeutic effects on subacute and chronic tinnitus of an inpatient multimodal treatment concept based on principles of Ericksonian hypnosis ( EH ) were examined by st and ardized criteria of the Tinnitus Question naire ( TQ ) and Health Survey ( SF-36 ) within a controlled prospect i ve , longitudinal study . A total of 393 patients were treated within an inpatient closed-group 28-day- setting based on a re source -oriented , hypnotherapeutic concept . The severity of tinnitus was assessed by TQ at times of admission , discharge and also at a 6- and 12-month follow-up . Health-related quality of life was evaluated before and after therapy using the SF-36 . After therapy , a decrease in TQ score was seen in 90.5 % of the patients with subacute tinnitus and in 88,3 % of those with chronic tinnitus . Assessment of the TQ score at the end of therapy revealed highly significant improvements of 15.9/14.1 points in mean . Effect sizes in the treatment groups ( 0.94/0.80 ) were superior to those in the waiting-list controls ( 0.14/0.23 ) . The TQ score remained stable in the follow-up controls . Significant improvement in health-related quality of life has been observed within the treatment groups depending on initial level of tinnitus serverity I – IV according to TQ . Using a multimodal treatment concept with emphasis on re source -activating approaches of EH the annoyance of tinnitus can be significantly reduced while health-related quality of life is enhanced within a comparatively short treatment period of 28 days 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 Since very little is understood about the exact aetiology of tinnitus , this has made treatment of the condition difficult . Even though approximately 10 - 15 % of the general population suffer from tinnitus , only 2 % consider it serious enough to warrant any treatment . The main problem arising from tinnitus is the disturbance it causes not only in day to day life but also in sleep , leading to fatigue and general discomfort . The present study focused on the effect of Melatonin in conjunction with Sulodexide as a treatment method for tinnitus . Overall , 102 patients suffering from tinnitus were evaluated in a prospect i ve r and omised controlled study conducted in a tertiary care ENT department . After r and omisation , 34 patients were treated with Melatonin and Sulodexide , another 34 were treated with Melatonin alone , while the remaining 34 ( control group ) were managed without treatment in order to evaluate spontaneous variations in the quality of tinnitus . Patients were assessed prospect ively with the Tinnitus H and icap Inventory and Acufenometry , both pre- and post-treatment . Among the patients studied , better results with both Tinnitus H and icap Inventory and Acufenometry were found in the group who received Melatonin and Sulodexide compared to those receiving Melatonin alone . No improvement was observed in the control group . In conclusion , Melatonin in combination with Sulodexide is , in our opinion , a viable treatment option for patients suffering from central or sensorineural tinnitus Objectives Question naires are essential for measuring tinnitus severity and intervention-related change but there is no st and ard instrument used routinely in research setting s. Most tinnitus question naires are optimised for measuring severity but not change . However , the Tinnitus Functional Index ( TFI ) cl aims to be optimised for both . It has not however been fully vali date d for research purpose s. Here we evaluate the relevant psychometric properties of the TFI , specifically the question naire factor structure , reproducibility , validity and responsiveness guided by quality criteria for the measurement properties of health-related question naires . Methods The study involved a retrospective analysis of data collected for 294 members of the general public who participated in a r and omised controlled trial of a novel tinnitus device ( Clinical Trials.gov Identifier : NCT01541969 ) . Participants completed up to eight commonly used assessment question naires including the TFI , Tinnitus H and icap Inventory ( THI ) , Tinnitus H and icap Question naire ( THQ ) , a Visual Analogue Scale of loudness ( VAS-Loudness ) , Percentage Annoyance question , the Beck 's Depression Inventory ( BDI ) , Beck 's Anxiety Inventory ( BAI ) , and the World Health Organisation Quality of Life-Bref ( WHOQOL-BREF ) . A series of analyses assessed the study objectives . Forty four participants completed the TFI at a second visit ( within 7–21 days and before receiving any intervention ) providing data for reproducibility assessment s. Results The 8-factor structure was not fully confirmed for this general ( non- clinical ) population . Whilst it was acceptable st and alone subscale , the ‘ auditory ’ factor showed poor loading with the higher order factor ‘ functional impact of tinnitus ’ . Reproducibility assessment s for the overall TFI indicate high internal consistency ( α = 0.80 ) and extremely high reliability ( ICC : 0.91 ) , whilst agreement was borderline acceptable ( 93 % ) . Construct validity was demonstrated by high correlations between scores on the TFI and THI ( r = 0.82 ) and THQ ( r = 0.82 ) , moderate correlations with VAS-L ( r = 0.46 ) , PR-A ( r = 0.58 ) , BDI ( r = 0.57 ) , BAI ( r = 0.39 ) and WHOQOL ( r = −0.48 ) . Floor effects were observed for more than 50 % of the items . A smallest detectable change score of 22.4 is proposed for the TFI global score . Conclusion Even though the proposed 8-factor structure was not fully confirmed for this population , the TFI appears to cover multiple symptom domains , and to measure the construct of tinnitus with an excellent reliability in distinguishing between patients . While the TFI may discriminate those whose tinnitus is not a problem , floor effects in many items means it is less appropriate as a measure of change in this subgroup . Further investigation is needed to determine whether these effects are relevant in other population The main component of tinnitus retraining therapy ( TRT ) is structured counseling . We conducted a r and omized clinical trial to test the hypothesis that group educational counseling based on TRT principles would effectively treat veterans who have clinical ly significant tinnitus . Veterans with clinical ly significant tinnitus were r and omized into one of three groups : educational counseling , traditional support , and no treatment . Subjects in the first two groups attended four 1.5 h group sessions each week . All subjects completed outcome question naires at baseline and at 1 , 6 , and 12 mo . A total of 269 subjects participated : 94 in the educational counseling group , 84 in the traditional support group , and 91 in the no-treatment group . Statistical analyses showed that educational counseling provided significantly more benefit than either traditional support or no treatment , as measured by the Tinnitus Severity Index . Results suggest that group educational counseling can significantly benefit many tinnitus patients and could be integral to a " progressive intervention " approach to tinnitus clinical management Objective The aim of this study was to investigate if cognitive behavior therapy ( CBT ) provided via the Internet results in significant decreases of distress in individuals with tinnitus . Methods Participants were recruited through Web pages and newspaper articles and thereafter r and omly allocated to a CBT self-help manual in six modules or to a waiting-list control group ( WLC ) . All treatment and contact with participants were conducted via the Internet with Web pages and E-mail correspondence . Participants were 117 individuals with tinnitus of duration of more than 6 months . In the first r and omized controlled phase of the study , 26 completed all stages of treatment ( 51 % dropout ) , and 64 of the WLC group completed measures . At 1-year follow-up , all participants had been offered the program and 96 provided outcome measures ( 18 % dropout rate from baseline ) . Tinnitus-related problems were assessed before and after treatment and at the 1-year follow-up . Daily diary ratings were included for 1 week before and 1 week following the treatment period . Results Tinnitus-related distress , depression , and diary ratings of annoyance decreased significantly . Immediately following the r and omized controlled phase ( with a WLC ) , significantly more participants in the treatment group showed an improvement of at least 50 % on the Tinnitus Reaction Question naire . At the uncontrolled follow-up , 27 ( 31 % ) of all participants had achieved a clinical ly significant improvement . Conclusions CBT via the Internet can help individuals decrease annoyance associated with tinnitus . High dropout rates or delay in completing treatment can be a characteristic of treatment studies using the Internet but should be contrasted with the cost effectiveness and accessibility of the Internet Background Tinnitus , the perception of sound in absence of an external acoustic source , impairs the quality of life in 2 % of the population . Since in most cases causal treatment is not possible , the majority of therapeutic attempts aim at developing and strengthening individual coping and habituation strategies . Therapeut Output:	RESULTS The evidence strongly favored a statistically significant decrease in the impact of tinnitus over time , though there was significant heterogeneity and clinical significance can not be interpreted . Outcome data regarding secondary measures did not demonstrate any clinical ly significant change . Participants allocated to the no-intervention or waiting-list control arm of clinical trials for a tinnitus intervention show a small but significant improvement in self-reported measures of tinnitus with time ; the clinical significance of this finding is unknown . There is , however , considerable variation across individuals .
MS22561	*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: From 1984 to 2001 , the Pediatric Oncology Group ( POG ) conducted 12 acute lymphoblastic leukemia ( ALL ) studies . Ten-year event-free survival ( EFS ) for patients > 12 months of age with B-precursor ALL on acute leukemia in children 14 , 15 and 16 series were 66.7±1.2 % , 68.1±1.4 % and 73.2±2.1 % , respectively . Intermediate dose methotrexate ( ID MTX ; 1 g/m2 ) improved outcomes for st and ard risk patients ( 10-year EFS 77.5±2.7 % vs 66.3±3.1 % for oral MTX ) . Neither MTX intensification ( 2.5 g/m2 ) nor addition of cytosine arabinoside/daunomycin/teniposide improved outcomes for higher risk patients . Intermediate dose mercaptopurine ( 1 g/m2 ) failed to improve outcomes for either group . Ten-year EFS for patients with T-cell ALL , POG 8704 and 9404 were 49.1±3.1 % and 72.2±4.7 % , respectively . Intensive asparaginase ( 10-year EFS 61.8 vs 42.7 % ) and high-dose MTX ( 5 g/m2 ) ( 10-year EFS 78.0 vs 65.8 % ) improved outcomes . There was a non-significant improvement in EFS for infants ( 10-year EFS 17.7±7.2–31.9±8.3 % ) . Prognostic indicators for B-precursor ALL were age and WBC at diagnosis , gender , central nervous system disease , DNA index and cytogenetic abnormalities . Only gender was prognostic in T-cell ALL . In infants , WBC and MLL translocation were linked to inferior outcome Summary Background We design ed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy ( ≥10 % viable tumour ) improved event-free survival in patients with high- grade osteosarcoma . Methods EURAMOS-1 was an open-label , international , phase 3 r and omised , controlled trial . Consenting patients with newly diagnosed , resectable , high- grade osteosarcoma aged 40 years or younger were eligible for r and omisation . Patients were r and omly assigned ( 1:1 ) to receive either postoperative cisplatin , doxorubicin , and methotrexate ( MAP ) or MAP plus ifosfamide and etoposide ( MAPIE ) using concealed permuted blocks with three stratification factors : trial group ; location of tumour ( proximal femur or proximal humerus vs other limb vs axial skeleton ) ; and presence of metastases ( no vs yes or possible ) . The MAP regimen consisted of cisplatin 120 mg/m2 , doxorubicin 37·5 mg/m2 per day on days 1 and 2 ( on weeks 1 and 6 ) followed 3 weeks later by high-dose methotrexate 12 g/m2 over 4 h. The MAPIE regimen consisted of MAP as a base regimen , with the addition of high-dose ifosfamide ( 14 g/m2 ) at 2·8 g/m2 per day with equidose mesna uroprotection , followed by etoposide 100 mg/m2 per day over 1 h on days 1–5 . The primary outcome measure was event-free survival measured in the intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT00134030 . Findings Between April 14 , 2005 , and June 30 , 2011 , 2260 patients were registered from 325 sites in 17 countries . 618 patients with poor response were r and omly assigned ; 310 to receive MAP and 308 to receive MAPIE . Median follow-up was 62·1 months ( IQR 46·6–76·6 ) ; 62·3 months ( IQR 46·9–77·1 ) for the MAP group and 61·1 months ( IQR 46·5–75·3 ) for the MAPIE group . 307 event-free survival events were reported ( 153 in the MAP group vs 154 in the MAPIE group ) . 193 deaths were reported ( 101 in the MAP group vs 92 in the MAPIE group ) . Event-free survival did not differ between treatment groups ( hazard ratio [ HR ] 0·98 [ 95 % CI 0·78–1·23 ] ) ; hazards were non-proportional ( p=0·0003 ) . The most common grade 3–4 adverse events were neutropenia ( 268 [ 89 % ] patients in MAP vs 268 [ 90 % ] in MAPIE ) , thrombocytopenia ( 231 [ 78 % in MAP vs 248 [ 83 % ] in MAPIE ) , and febrile neutropenia without documented infection ( 149 [ 50 % ] in MAP vs 217 [ 73 % ] in MAPIE ) . MAPIE was associated with more frequent grade 4 non-haematological toxicity than MAP ( 35 [ 12 % ] of 301 in the MAP group vs 71 [ 24 % ] of 298 in the MAPIE group ) . Two patients died during postoperative therapy , one from infection ( although their absolute neutrophil count was normal ) , which was definitely related to their MAP treatment ( specifically doxorubicin and cisplatin ) , and one from left ventricular systolic dysfunction , which was probably related to MAPIE treatment ( specifically doxorubicin ) . One suspected unexpected serious adverse reaction was reported in the MAP group : bone marrow infa rct ion due to methotrexate . Interpretation EURAMOS-1 results do not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma because its administration was associated with increased toxicity without improving event-free survival . The results define st and ard of care for this population . New strategies are required to improve outcomes in this setting . Funding UK Medical Research Council , National Cancer Institute , European Science Foundation , St Anna Kinderkrebsforschung , Fonds National de la Recherche Scientifique , Fonds voor Wetenschappelijk Onderzoek-Vla and eren , Parents Organization , Danish Medical Research Council , Academy of Finl and , Deutsche Forschungsgemeinschaft , Deutsche Krebshilfe , Federal Ministry of Education and Research , Semmelweis Foundation , ZonMw ( Council for Medical Research ) , Research Council of Norway , Sc and inavian Sarcoma Group , Swiss Paediatric Oncology Group , Cancer Research UK , National Institute for Health Research , University College London Hospitals , and Biomedical Research Centre PURPOSE To determine the cardioprotective effect of dexrazoxane ( DZR ) used in a doxorubicin-based combination therapy in advanced breast cancer . PATIENTS AND METHODS Between November 1988 and January 1991 , 534 patients with advanced breast cancer were r and omized to two multicenter , double-blind studies ( 088001 and 088006 ) . Patients received fluorouracil , doxorubicin , and cyclophosphamide ( FAC ) with either DZR ( DZR-to-doxorubicin ratio , 10:1 ) or placebo ( PLA ) every 3 weeks and were monitored with serial multiplegated acquisition ( MUGA ) scans . RESULTS The hazards ratio ( HR ) of PLA to DZR for a cardiac event , which was predefined ejection fraction changes or congestive heart failure ( CHF ) , was 2.63 ( 95 % confidence interval [ CI ] , 1.61 to 4.27 ; P < .001 ) for 088001 and 2.00 ( 95 % CI , 1.01 to 3.96 ; P = .038 ) for 088006 . The objective response rates for 088001 were 46.8 % for DZR and 60.5 % for PLA , a difference of 14 % ( 95 % CI , -25 % to -2 % ; P = .019 ) , and for 088006 were 53.7 % for DZR and 49.3 % for PLA , a difference of 4 % ( 95 % CI , -13 % to 22 % ; P = .63 ) . Time to progression and survival were not significantly different between treatment arms in either study . Toxicities on the DZR arms included lower granulocyte and platelet counts at nadir ( P = .009 and P = .004 , respectively ) and more pain on injection ( P = .001 ) , with no difference in the rates of fever , infection , or hemorrhage . CONCLUSION DZR had a significant cardioprotective effect as measured by noninvasive testing and clinical CHF . One of the two studies ( 088001 ) showed a lower response rate with DZR , but time to progression and survival were not significantly different . DZR is the first agent shown to reduce cardiotoxicity from doxorubicin Doxorubicin is an effective agent for many malignancies . To limit cardiotoxicity , doxorubicin can be given as prolonged infusion ( PIDX ) or bolus infusion following dexrazoxane ( DZX ) . The authors report their institutional experience comparing PIDX and DZX in a sarcoma cohort . Retrospective record review for newly diagnosed sarcoma patients at the University of Texas M.D. And erson Cancer Center from June 1998 to June 2006 . There were 23 Ewing 's sarcoma ( EWS ) patients treated with DZX and 40 osteosarcoma ( OS ) patients treated with PIDX . The DZX group had higher mean cumulative anthracycline dose ( 510 mg/m2 [ SD 120 mg/m2 ] versus 414 mg/m2 [ SD 99 mg/m2 ] , P = .002 ) , however mean lowest left ventricular ejection fraction ( EF ) values were higher for DZX ( 52.5 % [ SD 5.6 % ] versus 47.2 % [ SD 10.9 % ] , P = .014 ) . Fifteen of 19 patients with cardiac dysfunction were PIDX patients ( P = .15 ) . Five PIDX patients required cardiac medication , and 1 patient died of congestive heart failure ( CHF ) . Sixteen patients with cardiac dysfunction had improvement , demonstrated by EF ≥ 50 % at last echocardiogram . Although not statistically significant , there were 4 DZX patients with cardiac dysfunction . Prospect i ve studies are required to determine which strategy has long-term advantages and if certain patients are at increased risk for cardiac dysfunction This manuscript describes the experience from registration until r and omisation for a cohort of 2260 patients with osteosarcoma who joined the EURAMOS-1 trial . This includes pre-operative chemotherapy and surgery . It sets out the practical issues in collaboration and in achieving r and omisation BACKGROUND Previous r and omized controlled trials that used the two-drug chemotherapy regimen of cisplatin and doxorubicin as the conventional arm showed no evidence of benefit from an increase in the number of agents or the length of treatment . It was then proposed that survival could be improved by increasing the planned dose intensity of cisplatin and doxorubicin . METHODS Previously untreated patients with nonmetastatic , high- grade , central osteosarcoma of an extremity were r and omly assigned to Regimen-C ( conventional treatment with six 3-week cycles of cisplatin [ 100 mg/m2 by 24-hour infusion ] and doxorubicin [ 25 mg/m2/day by 4-hour infusion for 3 days ] ) or to Regimen-DI ( intensified treatment with identical total doses of cisplatin and doxorubicin , planned as six 2-week cycles supported by granulocyte colony stimulating factor ( G-CSF ) . Surgery was scheduled for week 6 in both arms . Primary and secondary outcome measures were overall and progression-free survival , respectively . Intention-to-treat analyses were performed using st and ard survival analysis methods . L and mark analyses were performed in patients with known surgical details and central ly review ed histologic response . All statistical tests were two-sided . RESULTS Between May 1993 and September 2002 , treatment was r and omly allocated to 497 eligible patients . Six cycles of chemotherapy were completed by 78 % of patients in Regimen-C and 80 % of patients in Regimen-DI . The delivered preoperative median dose intensity of cisplatin was 86 % in Regimen-C and 111 % in Regimen-DI ( as the percentage of that planned for the conventional regimen ) . Postoperative median dose intensity of cisplatin was 82 % in Regimen-C and 110 % in Regimen-DI ( the corresponding figures for doxorubicin dose intensity were similar ) . Regimen-DI was associated with lower risks of severe leucopenia and neutropenia and higher risks of thrombocytopenia and mucositis . Good histologic response ( > Output:	On the basis of our model , current dosing regimens — doxorubicin doses > 375 mg/m2 without dexrazoxane — overvalue increased anthracycline administration and may contribute to devastating cardiotoxicity .
MS22562	*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 proliferation marker Ki67 has been suggested as a promising cancer biomarker . As Ki67 needs an exact quantification , this marker is a prototype of a new generation of tissue-based biomarkers . In this study , we have systematic ally evaluated different cut points for Ki67 using three different clinical end points in a large neoadjuvant study cohort . PATIENTS AND METHODS We have evaluated pretherapeutic Ki67 levels by immunohistochemistry in 1166 breast cancer core biopsies from the neoadjuvant GeparTrio trial . We used the st and ardized cutoff-finder algorithm for three end points [ response to neoadjuvant chemotherapy ( pCR ) , disease-free ( DFS ) and overall-survival ( OS ) ] . The analyses were stratified for hormone receptor ( HR ) and HER2 status by molecular subtype radar diagrams ( MSRDs ) . RESULTS A wide range of Ki67 cut points between 3%-94 % ( for pCR ) , 6%-46 % ( for DFS ) and 4%-58 % ( for OS ) were significant . The three groups of Ki67 ≤ 15 % versus 15.1%-35 % versus > 35 % had pCR-rates of 4.2 % , 12.8 % , and 29.0 % ( P < 0.0005 ) , this effect was also present in six of eight molecular subtypes . In MSRD , Ki67 was significantly linked to prognosis in uni- and multivariate analysis in the complete cohort and in HR-positive , but not triple-negative tumors . CONCLUSIONS Ki67 is a significant predictive and prognostic marker over a wide range of cut points suggesting that data -derived cut point optimization might not be possible . Ki67 could be used as a continuous marker ; in addition , the scientific community could define st and ardized cut points for Ki67 . Our analysis explains the variability observed for Ki67 cut points in previous studies ; however , this should not be seen as weakness , but as strength of this marker . MSRDs are an easy new approach for visualization of biomarker effects on outcome across molecular subtypes in breast cancer . The experience with Ki67 could provide important information regarding the development and implementation of other quantitative biomarkers BACKGROUND The biological basis for the superior efficacy of neoadjuvant letrozole versus tamoxifen for postmenopausal women with estrogen receptor (ER)-positive locally advanced breast cancer was investigated by analyzing tumor proliferation and expression of estrogen-regulated genes before and after the initiation of therapy . METHODS Tumor sample s were obtained at baseline and at the end of treatment from 185 patients participating in a double blind r and omized Phase III study of neoadjuvant endocrine therapy . These paired specimens were simultaneously analyzed for Ki67 , ER , progesterone receptor ( PgR ) , trefoil factor 1 ( PS2 ) , HER1 ( epidermal growth factor receptor ) , and HER2 ( ErbB2 or neu ) by semiquantitative immunohistochemistry . RESULTS The treatment-induced reduction in geometric mean Ki67 was significantly greater with letrozole ( 87 % ) than tamoxifen ( 75 % ; analysis of covariance P = 0.0009 ) . Differences in the average Ki67 reduction were particularly marked for ER-positive tumors that overexpressed HER1 and /or HER2 ( 88 versus 45 % , respectively ; P = 0.0018 ) . Twenty-three of 92 tumors ( 25 % ) on tamoxifen and 14 of 93 on letrozole ( 15 % ) showed a paradoxical increase in Ki67 with treatment , and the majority of these cases was HER1/2 negative . Letrozole , but not tamoxifen , significantly reduced expression of the estrogen-regulated proteins PgR and trefoil factor 1 , regardless of HER1/2 status ( P < 0.0001 ) . ER down-regulation occurred with both agents , although levels decreased more with tamoxifen ( P < 0.0001 ) . CONCLUSION Letrozole inhibited tumor proliferation to a greater extent than tamoxifen . The molecular basis for this advantage appears complex but includes possible tamoxifen agonist effects on the cell cycle in both HER1/2 + and HER1/2- tumors . A pattern of continued proliferation despite appropriate down-regulation of PgR expression with estrogen deprivation or tamoxifen was also documented . This observation suggests the estrogenic regulation of proliferation and PgR expression may be dissociated in endocrine therapy resistant cells Background Expression of aromatase by malignant breast epithelial cells and /or the surrounding stroma implies local estrogen production that could influence the outcome of endocrine therapy for breast cancer . Methods A vali date d immunohistochemical assay for aromatase was applied to sample s from the P024 neoadjuvant endocrine therapy trial that compared tamoxifen and letrozole . The presence of aromatase expression by tumor or stromal cells was correlated with tumor response , treatment induced changes in proliferation index ( Ki67 ) , relapse-free survival ( RFS ) and breast cancer-specific survival ( BCSS ) . Results Tumor and stromal aromatase expression were highly correlated ( P = 0.0001 ) . Tumor cell aromatase , as a semi-continuous score , also correlated with smaller tumor size at presentation ( P = 0.01 ) higher baseline ER Allred score ( P = 0.006 ) and lower Ki67 levels ( P = 0.003 ) . There was no significant relationship with clinical response or treatment-induced changes in Ki67 . However , in a Cox multivariable model that incorporated a post-treatment tumor profile ( pathological T stage , N stage , Ki67 and ER status of the surgical specimen ) , the presence of tumor aromatase expression at baseline sample remained a favorable independent prognostic biomarker for both RFS ( P = 0.01 , HR 2.3 , 95 % CI 1.2–4.6 for absent expression ) and BCSS ( P = 0.008 , HR 3.76 , 95 % CI 1.4–10.0 ) . Conclusions Autocrine estrogen synthesis may be most characteristic of smaller , more indolent and ER-rich breast cancers with lower baseline growth rates . However , response to endocrine treatment may not depend on whether the estrogenic stimulus has a local versus systemic source Background : The National Epirubicin Adjuvant Trial ( NEAT ) and BR9601 trials tested the benefit of epirubicin when added to cyclophosphamide , methotrexate and 5-fluorouracil ( E-CMF ) compared with st and ard CMF in adjuvant chemotherapy for women with early breast cancer . This report details longer follow-up with interesting additional time-dependent analyses . Methods : National Epirubicin Adjuvant Trial used epirubicin ( E ) 3-weekly for four cycles followed by classical ( c ) CMF for four cycles ( E-CMF ) compared with cCMF for six cycles . BR9601 used E 3-weekly for four cycles followed by CMF 3-weekly for four cycles , compared with CMF 3-weekly for eight cycles . Results : In all , 2391 eligible patients were r and omised and with a median 7.4-year follow-up , E-CMF confirmed a significant benefit over CMF in both relapse-free survival ( RFS ) ( 78 % vs 71 % 5 years RFS , respectively , hazard ratio (HR)=0.75 ( 95 % CI : 0.65–0.86 ) , P<0.0001 ) and overall survival ( OS ) ( 84 % vs 78 % 5 years OS , respectively , HR=0.76 ( 95 % CI : 0.65–0.89 ) , P=0.0007 ) . Interaction of treatment effect and prognostic factors was demonstrated for duplication of chromosome 17 centromeric enumeration ( Ch17CEP ) as previously reported . Poor prognostic factors at diagnosis ( ER and PR negative and HER2 positive ) showed time-dependent annual hazard rates for RFS and OS . In univariate analysis , these factors demonstrated more favourable HRs for RFS after 5 years . Treatment effects also suggested a differential benefit for E-CMF within the first 5 years for poor prognosis tumours . Conclusion : Longer follow-up has confirmed E-CMF as significantly superior to CMF for all patients . Ch17CEP duplication was the only biomarker that demonstrated significant treatment interaction . St and ard poor prognostic factors at diagnosis were time-dependent , and after 5 years disease-free , poor prognosis patients demonstrated favourable HRs for survival BACKGROUND We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer . METHODS The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks ( group 1 ) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel ( group 2 ) . The North Central Cancer Treatment Group trial N9831 compared three regimens : doxorubicin and cyclophosphamide followed by weekly paclitaxel ( group A ) , the same regimen followed by 52 weeks of trastuzumab after paclitaxel ( group B ) , and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel ( group C ) . The studies were amended to include a joint analysis comparing groups 1 and A ( the control group ) with groups 2 and C ( the trastuzumab group ) . Group B was excluded because trastuzumab was not given concurrently with paclitaxel . RESULTS By March 15 , 2005 , 394 events ( recurrent , second primary cancer , or death before recurrence ) had been reported , triggering the first scheduled interim analysis . Of these , 133 were in the trastuzumab group and 261 in the control group ( hazard ratio , 0.48 ; P<0.0001 ) . This result crossed the early stopping boundary . The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years . Trastuzumab therapy was associated with a 33 percent reduction in the risk of death ( P=0.015 ) . The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831 . CONCLUSIONS Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer . ( Clinical Trials.gov numbers , NCT00004067 and NCT00005970 . Purpose : We have shown that DNA methylation of the PITX2 gene predicts risk of distant recurrence in steroid hormone receptor-positive , node-negative breast cancer . Here , we present results from a multicenter study investigating whether PITX2 and other c and i date DNA methylation markers predict outcome in node-positive , estrogen receptor-positive , HER-2-negative breast cancer patients who received adjuvant anthracycline-based chemotherapy . Experimental Design : Using a microarray platform , we analyzed DNA methylation in regulatory regions of PITX2 and 60 additional c and i date genes in 241 breast cancer specimens . Using Cox regression analysis , we assessed the predictive power of the individual marker/marker panel c and i date s. Clinical endpoints were time to distant metastasis , disease-free survival , and overall survival . A nested bootstrap/cross-validation strategy was applied to identify and vali date marker panels . Results : DNA methylation of PITX2 and 14 other genes was correlated with clinical outcome . In multivariate models , each methylation marker added significant information to established clinical factors . A four-marker panel including PITX2 , BMP4 , FGF4 , and C20orf55 was identified that result ed in improvement of outcome prediction compared with PITX2 alone . Conclusions : This study provides further evidence for the PITX2 biomarker , which has now been successfully confirmed to predict outcome among different breast cancer patient population s. We further identify new DNA methylation biomarkers , three of which can be combined into a panel with PITX2 to increase the outcome prediction performance in our anthracycline-treated primary breast cancer population . Our results show that a well-defined panel of DNA methylation markers enables outcome prediction in lymph node-positive , HER-2-negative breast cancer patients treated with anthracycline-based chemotherapy Abstract This r and omized , multicenter study compared the efficacy of docetaxel with or without capecitabine following fluorouracil/epirubicin/cyclophosphamide ( FEC ) therapy in operable breast cancer and investigated the role of Ki67 as a predictive biomarker . Patients were r and omized to 4 cycles of docetaxel/capecitabine ( docetaxel : 75 mg/m2 on day 1 ; capecitabine : 1,650 mg/m2 on days 1–14 every 3 weeks ) or docetaxel alone ( 75 mg/m2 on day 1 Output:	The use of these prognostic biomarkers should increase the options available for treatment algorithms
MS22563	*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 examined the prevalence of impaired glucose metabolism and its association with inflammation and insulin resistance ( IR ) in acute myocardial infa rct ion ( AMI ) patients without a previous diagnosis of diabetes . This prospect i ve study enrolled 52 AMI patients , and 75-g oral glucose tolerance testing was performed on 30 patients at discharge and again 3 months later . We also measured serum adiponectin , high sensitive C-reactive protein , and IL-6 on both occasions . Data were compared with those of 30 type 2 diabetic patients without a history of AMI . Forty percent and 36.7 % of AMI patients had impaired glucose tolerance ( IGT ) at discharge and at 3 months , respectively . The corresponding proportions for newly diagnosed diabetes are 33.0 % and 30.0 % . At discharge , AMI patients with IGT or diabetes showed higher high sensitive C-reactive protein and IL-6 levels compared with AMI patients with normal glucose tolerance or control type 2 diabetic patients . Furthermore , AMI patients with IGT or diabetes exhibited higher IR and lower serum adiponectin levels than AMI patients with normal glucose tolerance at 3 months after discharge . Previously undiagnosed diabetes and IGT are common in Korean patients with AMI . These glycometabolic abnormalities are associated with inflammation , IR , and serum adiponectin levels Background A high prevalence of impaired glucose tolerance and unknown type 2-diabetes in patients with coronary heart disease and no previous diagnosis of diabetes have been reported . The aims of the present study were to investigate the prevalence of abnormal glucose regulation ( AGR ) 3 months after an acute ST-elevation myocardial infa rct ion ( STEMI ) in patients without known glucometabolic disturbance , to evaluate the reliability of a 75-g oral glucose tolerance test ( OGTT ) performed very early after an acute STEMI to predict the presence of AGR at 3 months , and to study other potential predictors measured in-hospital for AGR at 3 months . Methods This was an observational cohort study prospect ively enrolling 224 STEMI patients treated with primary PCI . An OGTT was performed very early after an acute STEMI and was repeated in 200 patients after 3 months . We summarised the exact agreement observed , and assessed the observed reproducibility of the OGTTs performed in-hospital and at follow up . The patients were classified into glucometabolic categories defined according to the World Health Organisation criteria . AGR was defined as the sum of impaired fasting glucose , impaired glucose tolerance and type 2-diabetes . Results The prevalence of AGR at three months was 24.9 % ( 95 % CI 19.1 , 31.4 % ) , reduced from 46.9 % ( 95 % CI 40.2 , 53.6 ) when measured in-hospital . Only , 108 of 201 ( 54 % ) patients remained in the same glucometabolic category after a repeated OGTT . High levels of HbA1c and admission plasma glucose in-hospital significantly predicted AGR at 3 months ( p < 0.001 , p = 0.040 , respectively ) , and fasting plasma glucose was predictive when patients with large myocardial infa rct ion were excluded ( p < 0.001 ) . Conclusion The prevalence of AGR in STEMI patients was lower than expected . HbA1c , admission plasma glucose and fasting plasma glucose measured in-hospital seem to be useful as early markers of longst and ing glucometabolic disturbance . An OGTT performed very early after a STEMI did not provide reliable information on long-term glucometabolic state and should probably not be recommended IMPORTANCE Physicians often perceive as futile intensive care interventions that prolong life without achieving an effect that the patient can appreciate as a benefit . The prevalence and cost of critical care perceived to be futile have not been prospect ively quantified . OBJECTIVE To quantify the prevalence and cost of treatment perceived to be futile in adult critical care . DESIGN , SETTING , AND PARTICIPANTS To develop a common definition of futile care , we convened a focus group of clinicians who care for critically ill patients . On a daily basis for 3 months , we surveyed critical care specialists in 5 intensive care units ( ICUs ) at an academic health care system to identify patients whom the physicians believed were receiving futile treatment . Using a multivariate model , we identified patient and clinician characteristics associated with patients perceived to be receiving futile treatment . We estimated the total cost of futile treatment by summing the charges of each day of receiving perceived futile treatment and converting to costs . MAIN OUTCOME AND MEASURE Prevalence of patients perceived to be receiving futile treatment . RESULTS During a 3-month period , there were 6916 assessment s by 36 critical care specialists of 1136 patients . Of these patients , 904 ( 80 % ) were never perceived to be receiving futile treatment , 98 ( 8.6 % ) were perceived as receiving probably futile treatment , 123 ( 11 % ) were perceived as receiving futile treatment , and 11 ( 1 % ) were perceived as receiving futile treatment only on the day they transitioned to palliative care . The patients with futile treatment assessment s received 464 days of treatment perceived to be futile in critical care ( range , 1 - 58 days ) , accounting for 6.7 % of all assessed patient days in the 5 ICUs studied . Eighty-four of the 123 patients perceived as receiving futile treatment died before hospital discharge and 20 within 6 months of ICU care ( 6-month mortality rate of 85 % ) , with survivors remaining in severely compromised health states . The cost of futile treatment in critical care was estimated at $ 2.6 million . CONCLUSIONS AND RELEVANCE In 1 health system , treatment in critical care that is perceived to be futile is common and the cost is substantial OBJECTIVE Our goal was to determine the association between r and om admission hyperglycemia and new diagnosis of diabetes after discharge in patients hospitalized with pneumonia . METHODS Clinical data , including the Pneumonia Severity Index , were prospect ively collected on all 2124 patients without diabetes admitted with pneumonia to 6 hospitals in Edmonton , Alberta , Canada . Admission glucose was classified as : normal ( 4.0 - 6.0 mmol/L , reference group ) versus mild ( 6.1 - 7.7 mmol/L ) , moderate ( 7.8 - 11.0 mmol/L ) , and severe ( 11.1 - 20.0 mmol/L ) stress hyperglycemia . New diagnosis of diabetes over 5 years was ascertained using well-vali date d criteria within linked administrative data bases . Multivariable Cox models were used , and sensitivity , specificity , and likelihood ratios were calculated . RESULTS Mean age was 68 years ; 1091 ( 51 % ) were male , and 1418 ( 67 % ) had stress hyperglycemia . Over 5 years , 194 ( 14 % ) with stress hyperglycemia were diagnosed with diabetes . Compared with the 45 of 706 ( 6 % ) incidences of diabetes in normal glycemia patients ( 4.0 - 6.0 mmol/L ) , a strong grade d increase in risk of new diabetes existed with increasing hyperglycemia : mild ( 59 of 841 [ 7 % ] ; adjusted hazard ratio [ aHR ] 1.09 ; 95 % confidence interval [ CI ] , 0.74 - 1.61 ) versus moderate ( 86 of 473 [ 18 % ] ; aHR 2.99 ; 95 % CI , 2.07 - 4.31 ) versus severe ( 49 of 104 [ 47 % ] ; aHR 11.43 ; 95 % CI , 7.50 - 17.42 ) . Among moderate-to-severe hyperglycemia ( ≥7.8 mmol/L ) patients , the sensitivity , specificity , and positive and negative likelihood ratios for new diabetes were 57 % , 77 % , 2.1 , and 0.6 , respectively , with a number-needed-to-evaluate of 5 to detect one new case of diabetes . CONCLUSION Moderate-to-severe r and om hyperglycemia in pneumonia patients admitted to the hospital is strongly associated with new diagnosis of diabetes . Opportunistic evaluation for diabetes may be warranted in this group 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 BACKGROUND Impaired motor and hormonal gastrointestinal functions have been implicated in the pathogenesis of acute pancreatitis . The aim of the present study was to investigate the predictive value of the Gastroparesis Cardinal Symptom Index and serum ghrelin in the development of clinical ly meaningful outcomes in patients with acute pancreatitis . METHODS This was a prospect i ve clinical study . The Gastroparesis Cardinal Symptom Index and serum ghrelin were measured for 48 h after hospitalization . Univariate and multivariate logistic regression analyses were conducted . RESULTS The Gastroparesis Cardinal Symptom Index total score alone on day 2 was a significant predictor of oral feeding intolerance in both unadjusted ( odds ratio 1.21 ( 1.01 - 1.46 ) , P = 0.04 ) and adjusted ( odds ratio 1.30 ( 1.01 - 1.69 ) , P = 0.05 ) analyses . Adding ghrelin to Gastroparesis Cardinal Symptom Index further improved prediction in both unadjusted ( odds ratio 1.26 ( 1.02 - 1.56 ) , P = 0.03 ) and adjusted ( odds ratio 1.53 ( 1.00 - 2.35 ) , P = Output:	The prevalence of new‐onset diabetes was not influenced by disease setting , follow‐up duration , or study design . In summary , this study found stepwise growth in the prevalence of new‐onset diabetes with increasing in‐hospital glucose concentration .
MS22564	*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 treatment of intermediate- to high-risk prostate cancer with radical radiotherapy is usually in combination with neoadjuvant and rogen deprivation therapy . The aim of the present trial was to investigate whether degarelix achieves comparable efficacy with that of goserelin plus bicalutamide as neoadjuvant therapy before radiotherapy . MATERIAL S AND METHODS The study was a r and omised , parallel-arm , active-controlled , open-label trial in 244 men with a UICC prostate cancer TNM category T2b-T4 , N0 , M0 , Gleason score ≥7 , or prostate-specific antigen ≥10 ng/ml and a total prostate volume > 30 ml , who were scheduled to undergo radical radiotherapy and in whom neoadjuvant and rogen deprivation therapy was indicated . Eligible patients received treatment with either monthly degarelix ( 240/80 mg ) or goserelin ( 3.6 mg ) for 12 weeks , the latter patients also receiving bicalutamide ( 50 mg ) for 17 days initially . The primary efficacy measure was the mean percentage reduction in total prostate volume from baseline at week 12 measured by transrectal ultrasound . The severity and relief of lower urinary tract symptoms were assessed by the International Prostate Symptom Score question naire . Quality of life was assessed by the eighth question of the International Prostate Symptom Score . About 50 % of the patients had moderate to severe lower urinary tract symptoms at baseline . RESULTS The total prostate volume decreased significantly from baseline to week 12 in both treatment groups , reaching -36.0 ± 14.5 % in degarelix-treated patients and -35.3 ± 16.7 % in goserelin-treated patients ( adjusted difference : -0.3 % ; 95 % confidence interval : -4.74 ; 4.14 % ) . At the end of the therapy , more degarelix- than goserelin-treated patients reported International Prostate Symptom Score decreases of ≥3 points ( 37 % versus 27 % , P = 0.21 ) . In addition , in patients with a baseline International Prostate Symptom Score of ≥13 , the magnitude of the decrease was larger in degarelix- ( n = 53 ) versus goserelin-treated patients ( n = 17 ) ( 6.04 versus 3.41 , P = 0.06 ) . CONCLUSIONS The efficacy of degarelix in terms of prostate shrinkage is non-inferior to that of goserelin plus bicalutamide . The added benefits of degarelix in terms of more pronounced lower urinary tract symptom relief in symptomatic patients could be the reflection of differences in the direct effects on extra-pituitary receptors in the lower urinary tract [ Clinical trials.gov ID : NCT00833248 ] Introduction : No studies to date have assessed the efficacy/tolerability of degarelix in the relief of lower urinary tract symptoms ( LUTS ) secondary to prostate cancer ( PrCa ) . Methods : Patients were r and omised to degarelix 240/80 mg or goserelin 3.6 mg + bicalutamide flare protection ( G+B ) ; both treatments were administered for 3 months . The primary endpoint was change in International Prostate Symptom Score ( IPSS ) at week 12 compared with baseline . Results : This study was stopped early due to recruitment difficulties . 40 patients received treatment ( degarelix n = 27 ; G+B n = 13 ) ; most had locally advanced disease and were highly symptomatic . Degarelix was non-inferior to G+B in reducing IPSS at week 12 in the full analysis set ( p = 0.20 ) ; the significantly larger IPSS reduction in the per- protocol analysis ( p = 0.04 ) was suggestive of superior reductions with degarelix . Significantly more degarelix patients had improved quality of life ( IPSS question ) at week 12 ( 85 vs. 46 % ; p = 0.01 ) . Mean prostate size reductions at week 12 were 42 versus 25 % for patients receiving degarelix versus G+B , respectively ( p = 0.04 ; post hoc analysis ) . Most adverse events were mild/moderate ; more degarelix patients experienced injection site reactions whereas more G+B patients had urinary tract infections/cystitis . Conclusion : In 40 men with predominantly locally advanced PrCa and highly symptomatic LUTS , degarelix was at least non-inferior to G+B in reducing IPSS at week 12 12 Background : Comparative effectiveness of the gonadotropin-releasing hormone ( GnRH ) blocker , degarelix , vs the GnRH agonist , leuprolide , was evaluated during a 1-year phase III trial ( CS21 ) ; data have been presented . We now report long-term data from an ongoing 5-year extension study ( CS21A ) . METHODS In CS21 , patients with prostate cancer ( all stages ) were r and omized to degarelix ( 240 mg for 1 month , then monthly maintenance doses of 80 mg [ n=207 ] or 160 mg [ n=202 ] ) , or leuprolide 7.5 mg/month ( n=201 ) . Leuprolide patients could receive bicalutamide . Of the 504 patients who completed the 1-year trial , 384 chose to continue in an extension study ; those on leuprolide were re-r and omized to degarelix 240/80 mg or 240/160 mg . PSA PFS was defined as time to first PSA failure ( two consecutive increases in PSA of 50 % and ≥5 ng/mL above nadir ) or death . Time for 25 % of patients to experience PSA PFS ( TTP25 % ) was analyzed using Weibull estimates . RESULTS Up to 1 year , the risk of PSA PFS was significantly lower with degarelix 240/80 mg vs leuprolide ( p=0.05 , log-rank ) . At 27.5 months ' median follow-up , hazard rate of PSA PFS significantly decreased in leuprolide patients switched to degarelix compared with before the switch ( 0.20 vs 0.08 ; p=0.003 ) . Similar improvements occurred in patients with baseline PSA > 20 ng/mL. During the first year , TTP25 % for patients with baseline PSA > 20 ng/mL was numerically longer with degarelix vs leuprolide ( 407 vs 303 days ; p=0.085 ) ; the difference was even greater when degarelix data were analyzed beyond 1 year ( 514 vs 303 days ; p=0.01 ) . CONCLUSIONS Patients receiving degarelix had a significantly lower risk of PSA failure or death vs leuprolide during the first year of treatment . After switching to degarelix , patients who initially received leuprolide experienced a significantly lower rate of PSA failure or death . In patients with baseline PSA > 20 ng/mL , TTP25 % was significantly longer for degarelix patients . These data support the durability of the significant PSA PFS benefit of degarelix vs monthly leuprolide observed during the first year and the use of degarelix as first-line and rogen deprivation therapy . [ Table : see text ] PURPOSE We assessed the cardiovascular safety profile of degarelix , a new gonadotropin-releasing hormone antagonist . MATERIAL S AND METHODS This is the first report to our knowledge on cardiovascular safety data from a completed 1-year r and omized controlled trial of leuprolide acetate vs degarelix . Outcomes considered in these analyses included the QT interval by central reading and analysis , and cardiovascular adverse events . On multivariate analyses relationships between selected baseline factors and cardiovascular events were evaluated . RESULTS There were no significant differences between treatment groups for mean change in Fridericia 's correction of QT during the trial . Markedly abnormal Fridericia 's correction of QT values ( 500 milliseconds or greater ) were observed in only a small number of subjects by treatment group , that is 2 ( less than 1 % ) in the pooled degarelix group and 2 ( 1 % ) in the leuprolide group . Supraventricular arrhythmias were the most common type of arrhythmias , affecting 2 % of subjects in the pooled degarelix group and 4 % in the leuprolide group . Other arrhythmias occurred in 1 % or less of subjects by treatment group . The most frequently reported cardiac disorder was ischemic heart disease , which occurred in 4 % of subjects treated with degarelix and 10 % of those on leuprolide . Cox proportional hazard ratio estimates for selected baseline covariates showed a significantly increased risk of cardiovascular events by age ( p=0.0459 ) and systolic blood pressure ( p=0.0061 ) . CONCLUSIONS In men with prostate cancer degarelix and leuprolide have similar cardiovascular safety profiles . These observations suggest that the cardiovascular events associated with both agents result from hypogonadism rather than a direct drug effect The aim of the study was to compare the onset , incidence and frequency/intensity of hot flushes during and rogen-deprivation therapy with a gonadotropin-releasing hormone antagonist ( GnRH ) blocker versus an agonist using data from a r and omized Phase 3 clinical trial . In total , 610 prostate cancer patients received monthly degarelix ( s.c . , 240/80 mg , n=207 , or 240/160 mg , n=202 ) or leuprolide ( i.m . , 7.5 mg , n=201 ) for 12 months . Data on hot flushes was collected as self-reported adverse events and in a subgroup of 254 patients with electronic diaries . The onset of hot flushes was faster on degarelix versus leuprolide , and was accompanied by higher median hot flush scores during the first 3 months . However , there were no significant differences in overall incidence rates and median hot flush scores over the entire 12 months . After the third month , incidence rates dropped below 6 % , whereas prevalence rates remained constant in all the three treatment arms . In multivariate analysis , body weight and heart rate at baseline were independent predictors of hot flushes ( P<0.05 ) . Except for a more rapid onset with the GnRH antagonist , there were no major differences in the overall pattern of hot flushes between treatment options . Weight control may help to minimize the incidence of hot flushes To evaluate the efficacy and safety of degarelix , a new gonadotrophin‐releasing hormone ( GnRH ) antagonist ( blocker ) , vs leuprolide for achieving and maintaining testosterone suppression in a 1‐year phase III trial involving patients with prostate cancer OBJECTIVE To investigate the effects of baseline testosterone on testosterone control and prostate-specific antigen ( PSA ) suppression using data from a phase III trial ( CS21 ) comparing degarelix and leuprolide in prostate cancer . METHODS In CS21 , patients with histologically confirmed prostate cancer ( all stages ) were r and omized to degarelix 240 mg for 1 month followed by monthly maintenance doses of 80 or 160 mg , or leuprolide 7.5 mg/month . Patients receiving leuprolide could receive anti and rogens for flare protection . Treatment effects on testosterone and PSA reduction , testosterone surge , and microsurges were investigated in 3 baseline testosterone subgroups : < 3.5 , 3.5 - 5.0 , and > 5.0 ng/mL. Data are presented for the groups receiving degarelix 240/80 mg ( the approved dose ) and leuprolide 7.5 mg . RESULTS Higher baseline testosterone delayed castration with both treatments . However , castrate testosterone levels and PSA suppression occurred more rapidly with degarelix irrespective of baseline testosterone . With leuprolide , the magnitude of testosterone surge and microsurges increased with increasing baseline testosterone . There was no overall correlation between baseline testosterone and initial PSA decrease in either treatment group , although PSA suppression tended to be slowest with leuprolide and fastest with degarelix in the high baseline testosterone subgroup . CONCLUSION Patients with high baseline testosterone may have greater risk of tumor stimulation ( clinical flare ) and mini-flares during gonadotrophin-releasing hormone agonist treatment and so the need for flare protection with anti and rogens in these patients is obvious , especially in metastatic disease . Although higher baseline testosterone delays castration , castrate testosterone and PSA suppression occur more rapidly with degarelix , irrespective of baseline testosterone , without the need for flare protection OBJECTIVES To evaluate whether switching prostate cancer ( PCa ) patients from leuprolide to degarelix is associated with any change in the efficacy of testosterone suppression or safety profile during the first 3 months . METHODS Participants were 134 patients with histologically confirmed PCa who had completed 1 year of treatment with leuprolide 7.5 mg monthly before being switched to degarelix . These patients were re-r and omised for the extension trial to receive a starting dose of 240 mg degarelix followed by monthly maintenance doses of either 80 ( n = 69 ) or 1 Output:	The risk for injection-site events was increased , but cardiovascular events may occur less often by using GnRH antagonist . There is currently insufficient evidence to make firm conclusive statements on the efficacy of GnRH antagonist compared to st and ard and rogen suppression therapy for advanced prostate cancer .
MS22565	*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 determine whether administration of Lactobacillus reuteri ( L reuteri ) DSM 17938 is beneficial in breastfed infants with infantile colic . STUDY DESIGN Eighty infants aged < 5 months with infantile colic ( defined as crying episodes lasting 3 or more hours per day and occurring at least 3 days per week within 7 days prior to enrollment ) , who were exclusively or predominantly ( > 50 % ) breastfed were r and omly assigned to receive L reuteri DSM 17938 ( 10(8 ) colony-forming units ) ( n = 40 ) or an identically appearing and tasting placebo ( n = 40 ) , both orally , in 5 drops , 1 time daily , for 21 days . The primary outcome measures were the treatment success , defined as the percentage of children achieving a reduction in the daily average crying time ≥ 50 % , and the duration of crying ( minutes per day ) at 7 , 14 , 21 , and 28 days after r and omization . RESULTS The rate of responders to treatment was significantly higher in the probiotic group compared with the placebo group at day 7 ( P = .026 ) , at day 14 ( relative risk ( RR ) 4.3 , 95 % CI 2.3 - 8.7 ) , at day 21 ( RR 2.7 , 95 % CI 1.85 - 4.1 ) , and at day 28 ( RR 2.5 , 95 % CI 1.8 - 3.75 ) . In addition , throughout the study period , the median crying time was significantly reduced in the probiotic group compared with the control group . CONCLUSION Exclusively or predominantly breastfed infants with infantile colic benefit from the administration of L reuteri DSM 17938 compared with placebo Objective : The aim of the study was to evaluate the effect of infant formula with polydextrose ( PDX ) and galacto-oligosaccharides ( GOS ) on fecal microbiota and secretory IgA ( sIgA ) . Material s and Methods : In the present double-blind , r and omized study , term infants received control ( Enfamil Lipil ) or the same formula with PDX/GOS ( 4 g/L , 1:1 ratio ; PDX/GOS ) for 60 days ; a reference breast-fed group was included . Formula intake , tolerance , and stool characteristics were collected via electronic diary and analyzed by repeated measures analysis of variance . Anthropometric measurements and stool sample s were obtained at baseline and after 30 and 60 days of feeding . Fecal sIgA was measured by enzyme-linked immunosorbent assay and fecal bacteria by fluorescent in situ hybridization and quantitative real-time polymerase chain reaction ( qPCR ) ; both were analyzed by Wilcoxon rank sum test . Results : Two hundred thirty infants completed the study . Infants consuming PDX/GOS had softer stools than control at all times ( P < 0.001 ) . Using qPCR , counts in PDX/GOS were closer to the breast-fed group , tended to be higher than control for total bifidobacteria ( P = 0.069 ) and Bifidobacterium longum ( P = 0.057 ) at 30 days , and were significantly higher for total bifidobacteria and B longum at 60 days and B infantis at 30 days ( P = 0.002 ) . No significant differences were detected between PDX/GOS and control in changes from baseline to 30 or 60 days for sIgA or total bifidobacteria by fluorescent in situ hybridization or qPCR ; however , significantly higher changes from baseline were detected between PDX/GOS and control for B infantis at 30 days and B longum at 60 days ( P ⩽ 0.035 ) . Conclusions : Infant formula with PDX/GOS produces soft stools and a bifidogenic effect closer to breast milk than formula without PDX/GOS Background : Colic , regurgitation and constipation are common feeding problems in formula‐fed infants that might benefit from dietary treatment . A formula containing fructo‐ and galacto‐oligosaccharides , partially hydrolysed proteins , low levels of lactose and palmitic acid in the β position and higher density has been tested to reduce the occurrence of these symptoms . The aim of this prospect i ve study was to describe the effects of such a formula in infants with minor gastrointestinal disorders . Methods : An observational prospect i ve trial involving practising Italian paediatricians was performed . Formula fed‐infants up to 90 d of age with minor gastrointestinal problems such as infantile colics and /or regurgitation and /or constipation were enrolled in the study from January 2001 to May 2001 . The study was completed within 14 d of treatment . On days 1 , 7 and 14 the infants were visited by the paediatricians . Parents were given a structured diary to record daily episodes of colic , regurgitation and type and number of stools . Results : Of the 932 infants enrolled , 604 completed the study . Of the 214 infants with colic , 169 ( 79 % ) demonstrated a reduction in frequency of colic from 4.1 ± 2.0 per day at the beginning of the study to 2.0 ± 1.8 at the end of the study ( I.C. 95 % : 1.72–2.39 ; p < 0.005 ) . A reduction in the number of episodes of colic of 1.8 per day at the beginning of the study ( I.C. 95 % : 1.49–2.11 ; p < 0.05 ) was recorded between day 1 and day 7 , and of 0.26 ( I.C. 95 % : 0.15–0.37 ; p < 0.05 ) between day 7 and day 14 . Of the 201 infants with regurgitation problems , 141 ( 70 % ) demonstrated a reduction of frequency of the symptoms from 4.2 ± 2.0 per day at the beginningof the study to 2.1 ± 2.2 at the end of the study ( I.C. 95 % : 1.75–2.35 ; p < 0.005 ) . A reduction of 1.87 in the number of regurgitation episodes was reported between day 1 and day 7 ( I.C. 95 % : 1.57–2.16 ; p < 0.05 ) and of 0.18 ( I.C. 95 % : 0.06–0.31 ; p < 0.05 ) between day 7 and day 14 . Of the 232 infants with constipation , 147 ( 63 % ) demonstrated an increase in the daily number of stools of 0.42 ( I.C. 95 % : 0.5–0.3 ; p < 0.005 ) . An increase in stool frequency of 0.41 ( I.C. 95 % : 0.51–0.23 ; p < 0.05 ) was reported between day 1 and day 7 , and of 0.04 ( I.C. 95 % : 0.22–0.14 ; p= ns ) between day 7 and day 14 . Parents’evaluation of the formula was 7.9 ± 1.8 ( score 0–10 ) ; 550 parents ( 91 % ) gave a positive judgement ( score > 6 ) . The evaluation by the paediatricians of the improvement in symptoms after the treatment was 8.2 ± 1.5 ; 574 ( 95 % ) a positive effect ( score > 6 ) Background : Oligosaccharides may alter postnatal immune development by influencing the constitution of gastrointestinal bacterial flora . Aims : To investigate the effect of a prebiotic mixture of galacto- and long chain fructo-oligosaccharides on the incidence of atopic dermatitis ( AD ) during the first six months of life in formula fed infants at high risk of atopy . Methods : Prospect i ve , double-blind , r and omised , placebo controlled trial ; 259 infants at risk for atopy were enrolled . A total of 102 infants in the prebiotic group and 104 infants in the placebo group completed the study . If bottle feeding was started , the infant was r and omly assigned to one of two hydrolysed protein formula groups ( 0.8 g/100 ml prebiotics or maltodextrine as placebo ) . All infants were examined for clinical evidence of atopic dermatitis . In a subgroup of 98 infants , faecal flora was analysed . Results : Ten infants ( 9.8 % ; 95 CI 5.4–17.1 % ) in the intervention group and 24 infants ( 23.1 % ; 95 CI 16.0–32.1 % ) in the control group developed AD . The severity of the dermatitis was not affected by diet . Prebiotic supplements were associated with a significantly higher number of faecal bifidobacteria compared with controls but there was no significant difference in lactobacilli counts . Conclusion : Results show for the first time a beneficial effect of prebiotics on the development of atopic dermatitis in a high risk population of infants . Although the mechanism of this effect requires further investigation , it appears likely that oligosaccharides modulate postnatal immune development by altering bowel flora and have a potential role in primary allergy prevention during infancy OBJECTIVE To investigate the effectiveness of Lactobacillus reuteri DSM 17938 for the treatment of infantile colic in breastfed Canadian infants , compared with placebo . STUDY DESIGN A r and omized , double-blind , placebo-controlled trial was conducted involving 52 infants with colic , according to modified Wessel criteria , who were assigned at r and om to receive L reuteri DSM 17938 ( 10(8 ) colony-forming units ) ( n = 24 ) or placebo ( n = 28 ) for 21 days . Daily crying and fussing times were recorded in a structured diary , and maternal question naires were completed to monitor changes in infant colic symptoms and adverse events . RESULTS Total average crying and fussing times throughout the study ( from baseline to day 21 ) were significantly shorter among infants with colic in the probiotic group compared with infants in the placebo group ( 1719 ± 750 minutes [ 29 ± 13 hours ] vs 2195 ± 764 minutes [ 37 ± 13 hours ] ; P = .028 ) ( relative risk , 0.78 ; 95 % CI , 0.58 - 0.98 ) . Infants given L reuteri DSM 17938 showed a significant reduction in daily crying and fussing times at the end of treatment period compared with those receiving placebo ( median , 60 minutes/day [ IQR , 64 minutes/day ] vs 102 minutes/day [ IQR , 87 minutes/day ] ; P = .045 ) . On day 21 , a significantly higher proportion of infants in the L reuteri DSM 17938 group responded to treatment with a ≥50 % crying time reduction compared with infants given placebo ( 17 vs 6 , P = .035 ; relative risk , 3.3 ; 95 % CI , 1.55 - 7.03 ) . CONCLUSION Administration of L reuteri DSM 17938 significantly improved colic symptoms by reducing crying and fussing times in breastfed Canadian infants with colic Background Human milk oligosaccharides have been shown to stimulate selectively the growth of Bifidobacteria and Lactobacilli in the intestine . In this study , the bifidogenic effect of an experimental prebiotic oligosaccharide mixture consisting of low-molecular-weight galactooligosaccharides and high-molecular-weight fructooligosaccharides was analyzed in 90 term infants . Methods Two test formulas were supplemented with either 0.4 g/dL or with 0.8 g/dL oligosaccharides . In the control formula , maltodextrin was used as placebo . At study day 1 and study day 28 , the fecal species , colony forming units ( cfu ) and pH were measured and stool characteristics , growth , and side effects were recorded . Results At study day 1 , the median number of Bifidobacteria did not differ among the groups ( 0.4 g/dL group , mean [ interquartile range ] 8.5 [ 1.9 ] cfu/g ; 0.8 g/dL group , 7.7 [ 6.1 ] cfu/g ; and the placebo group , 8.8 [ 6.1 ] cfu/g ) ( figures in square brackets are interquartile range ) . At the end of the 28-day feeding period , the number of Bifidobacteria was significantly increased for both groups receiving supplemented formulas ( the 0.4 g/dL group , 9.3 [ 4.9 ] cfu/g ; the 0.8 g/dL group , 9.7 [ 0.8 ] cfu/g ) versus the placebo group ( 7.2 [ 4.9 ] cfu/g , P < 0.001 ) . This effect was dose dependent ( 0.4 g/dL versus 0.8 g/dL , P < 0.01 ) . The number of Lactobacilli also increased significantly in both groups fed the supplemented formulas ( versus placebo , P < 0. Output:	SYNTHESIS OF RESULTS Infants frequently show several gastrointestinal signs and symptoms . During the normal development of the digestive tract , several gastrointestinal signs and symptoms may occur , usually result ing from functional gastrointestinal disorders , gastroesophageal reflux disease , and allergy to cow 's milk protein .
MS22566	*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 To develop a checklist of items measuring the quality of reports of r and omized clinical trials ( RCTs ) assessing nonpharmacological treatments ( NPTs ) . STUDY DESIGN AND SETTING The Delphi consensus method was used to select and reduce the number of items in the checklist . A total of 154 individuals were invited to participate : epidemiologists and statisticians involved in the field of methodology of RCTs ( n = 55 ) , members of the Cochrane Collaboration ( n = 41 ) , and clinicians involved in planning NPT clinical trials ( n = 58 ) . Participants ranked on a 10-point Likert scale whether an item should be included in the checklist . RESULTS Fifty-five experts ( 36 % ) participated in the survey . They were experienced in systematic review s ( 68 % were involved in the Cochrane Collaboration ) and in planning RCTs ( 76 % ) . Three rounds of the Delphi method were conducted to achieve consensus . The final checklist contains 10 items and 5 subitems , with items related to the st and ardization of the intervention , care provider influence , and additional measures to minimize the potential bias from lack of blinding of participants , care providers , and outcome assessors . CONCLUSIONS This tool can be used to critically appraise the medical literature , design NPT studies , and assess the quality of trial reports included in systematic review Abstract Objectives Firstly , to compare the effectiveness of a brief physiotherapy intervention with “ usual ” physiotherapy for patients with neck pain . Secondly , to evaluate the effect of patients ' preferences on outcome . Design Non-inferiority r and omised controlled trial eliciting preferences independently of r and omisation . Setting Physiotherapy departments in a community setting in Yorkshire and north Lincolnshire . Participants 268 patients ( mean age 48 years ) with subacute and chronic neck pain , who were referred by their general practitioner and r and omly assigned to a brief physiotherapy intervention ( one to three sessions ) using cognitive behaviour principles to encourage self management and return to normal function or usual physiotherapy , at the discretion of the physiotherapist concerned . Main outcome measures The Northwick Park neck pain question naire ( NPQ ) , a specific measure of functional disability result ing from neck pain . Also , the short form 36 ( SF-36 ) question naire , a generic , health related , quality of life measure ; and the Tampa scale for kinesophobia , a measure of fear and avoidance of movement . Results At 12 months , patients allocated to usual physiotherapy had a small but significant improvement in NPQ scores compared with patients in the brief intervention group ( mean difference 1.99 , 95 % confidence interval 0.45 to 3.52 ; P = 0.01 ) . Although the result shows a significant inferiority of the intervention , the confidence interval shows that the effect could be in the non-inferiority range for the brief intervention ( below 1.2 points of NPQ score ) . Patients who preferred the brief intervention and received this treatment had similar outcomes to patients receiving usual physiotherapy . Conclusions Usual physiotherapy may be only marginally better than a brief physiotherapy intervention for neck pain . Patients with a preference for the brief intervention may do at least as well with this approach . Additional training for the physiotherapists in cognitive behaviour techniques might improve this approach further Study Design . A question naire was mailed to 3000 r and omly selected 35‐45‐year‐old individuals in three communities in central Sweden . Objectives . To study the 1‐year prevalence of spinal pain and its ramifications in the form of pain , function , sick leave , and health care use . Summary of Background Data . Previous research ers have used a variety of definitions and population s , but primarily have investigated the occurrence of pain . Comprehensive data are needed concerning health care use , the degree of the pain problem , functional disturbances , and sick leave . Method . Participants in the study completed a question naire regarding spinal pain during the past year including the degree of their experienced pain , functional impairment , lost work days , and health care use . Results . A total of 2305 people ( 78.5 % ) responded to the question naire . Nonrespondents had similar characteristics but a slightly lower 1‐year prevalence rate than did respondents . For respondents , the prevalence of spinal pain during the past year was 66.3 % , with women having a slightly higher prevalence than men . Approximately 25 % of the respondents indicated that they had a substantial problem based on ratings of pain , functional impairment , and sick leave . Work absenteeism reported to the Public Social Insurance Office involved 19 % of those with pain , but an additional 15 % indicated unreported absenteeism . On average , those with pain visited health care providers three times during the past year , but a small number of those who experienced pain consumed large amounts of health care and illness benefits . An important gender difference was shown , such that when pain was at its worst , men took sick leave , whereas women sought health care . Conclusions . Taken together , these data indicate that spinal pain is common among 35‐45‐year‐old men and ‐ women , and that it is related to marked problems for approximately one fourth of those who experience pain . Gender differences exist in the pattern of sick leave and health care use , and a small proportion of those with pain consume very large amounts of the re sources . Consequently , there is a need for early , effective , preventive treatments OBJECTIVE To study the effect of manual therapy and stretching on neck function in women with chronic neck pain . METHODS A total of 125 women were r and omized into 2 groups . Group 1 received manual therapy twice a week for 4 weeks followed by stretching exercises . Group 2 performed stretching 5 times a week for 4 weeks followed by manual therapy . Neck function was assessed by isometric neck strength and mobility measurements , and spontaneous neck pain during the past week and strain-evoked pain during the neck strength trials using a visual analogue scale . RESULTS Both neck muscle strength ( 11 - 14 % ) and mobility ( 7 - 15 % ) improved similarly in both groups , with the exception of greater passive flexion-extension mobility ( p = 0.019 ) in group 1 at week 4 . Pain during the neck strength trials decreased from the baseline to week 4 by 26 - 35 % and to week 12 by 39 - 61 % similarly in both groups . Average neck pain during the past week decreased by 64 % and 53 % in groups 1 and 2 , respectively , during the first 4 weeks , remaining rather stable thereafter . The decreases in neck pain during both the past week and strength trials showed association with the changes in neck strength results ( r = 0.20 - 0.29 ) . CONCLUSION Both manual therapy and stretching were effective short-term treatments for reducing both spontaneous and strain-evoked pain in patients with chronic neck pain . It is possible that the decrease in pain reduced inhibition of the motor system and in part improved neck function . However , the changes in neck muscle strength were minor , showing that these treatments alone are not effective in improving muscle strength We studied the clinical effectiveness of botulinum toxin type A for spasmodic torticollis and that for facial spasm by multicenter , non-blinded study . The freeze-dried crystalline botulinum toxin type A ( AGN 191622 ; Allergan Inc. , Irvine , CA ) was injected into the hyperactive muscles and the clinical course was followed for 22 weeks . Repeated injections were done , if necessary , with an interval of 4 weeks . The toxin was highly effective in both disorders . In spasmodic torticollis , clinical severity improved in 38 ( 63.3 % ) and the global improvement was seen in 39 ( 65.0 % ) out of 60 patients . Subjective improvement was seen in 56 ( 93.3 % ) . In facial spasm , 52 ( 92.9 % ) out of 56 patients improved after the treatment . Unfavorable reactions , mainly consisting of neck muscle weakness and dysphagia in torticollis and facial weakness in facial spasm , were mostly due to the excessive action of the toxin . They were usually mild and transient . No patients discontinued the trial because of side effects . Botulinum toxin injection is a very useful and safe method for the symptomatic treatment of spasmodic torticollis and facial spasm Successful treatment of torticollis with electromyographic ( EMG ) biofeedback has been reported in a number of single case and single group studies . The present investigation represents the first controlled outcome study . Twelve torticollis patients were r and omly assigned to EMG biofeedback or relaxation training and grade d neck exercises ( RGP ) . The procedure involved three sessions of baseline assessment , 15 sessions of EMG BF or RGP , 6 sessions of EMG BF or RGP plus home-management , 6 sessions of home-management alone , and follow-up 3 months after the end of treatment . A variety of outcome measures were used including physiological ( EMG from the two sternocleidomastoid muscles , skin conductance level ) , behavioral ( angle of head deviation , range of movement of the head ) , and self-report ( depression , functional disability , body concept ) , therapist and “ significant other ” reports and independent observer assessment of videos . In both groups , neck muscle activity was reduced from pre- to posttreatment . This reduction was greater in the EMG biofeedback group . There was evidence of feedback-specific neck muscle relaxation in the EMG biofeedback group . Therefore , the outcome was not due to nonspecific factors and could be attributed to feedback-specific effects . Changes in skin conductance level showed that neck muscle relaxation was not simply mediated by a general reduction of “ arousal . ” Significant improvements of extent of head deviation , and range of movement of the head , as well as reductions of depression were present , which were not different in the two groups . At the end of treatment , no patient was asymptomatic . Any therapeutic benefit was generally maintained at follow-up . The results and the procedural simplicity of RGP make the issue of cost-efficacy of EMG biofeedback a pertinent one . Further controlled outcome studies of EMG biofeedback treatment of torticollis with larger sample s are required PURPOSE To study whether the isolated intervention of high-speed , low-amplitude spinal manipulation in the cervical spine has any effect on cervicogenic headache . DESIGN Prospect i ve r and omized controlled trial with a blinded observer . SETTING Ambulatory outpatient facility in an independent research institution . PARTICIPANTS Fifty-three subjects suffering from frequent headaches who fulfilled the International Headache Society criteria for cervicogenic headache ( excluding radiological criteria ) . These subjects were recruited from 450 headache sufferers who responded to newspaper advertisements . INTERVENTION After r and omization , 28 of the group received high-velocity , low-amplitude cervical manipulation twice a week for 3 wk . The remaining 25 received low-level laser in the upper cervical region and deep friction massage ( including trigger points ) in the lower cervical/upper thoracic region , also twice a week for 3 wk . MAIN OUTCOME MEASURES The change from week 1 to week 5 in analgesic use per day , in headache intensity per episode and in number of headache hours per day , as registered in a headache diary . RESULTS The use of analgesics decreased by 36 % in the manipulation group , but was unchanged in the soft-tissue group ; this difference was statistically significant ( p = .04 , chi 2 for trend ) . The number of headache hours per day decreased by 69 % in the manipulation group , compared with 37 % in the soft-tissue group ; this was significant at p = .03 ( Mann-Whitney ) . Finally , headache intensity per episode decreased by 36 % in the manipulation group , compared with 17 % in the soft-tissue group ; this was significant at p = .04 ( Mann-Whitney ) . CONCLUSION Spinal manipulation has a significant positive effect in cases of cervicogenic headache OBJECTIVE This study evaluates the effectiveness of traditional bone setting ( TBS ) in chronic neck pain ( cNP ) compared with conventional physiotherapy ( PT ) and massage ( M ) . METHODS This was a r and omized clinical trial . Working-aged employed subjects with cNP ( n = 105 ; 37 men and 68 women ; mean age , 41.5 years ) were r and omized into TBS , PT , and M groups . Follow-up times were 1 , 6 , and 12 months after the treatments . Neck pain intensity ( visual analog scale ) , perceived disability ( Neck Disability Index [ NDI ] ) , and neck spine mobility measurements were used as outcomes . Global assessment was evaluated by the subjects ( scale from -1 to + 10 ) . Data were analyzed using time ( pre and post ) by group ( TBS , PT and M ) , 2- way analysis of variance for repeated measures . RESULTS Neck pain decreased and NDI scores improved in all groups 1 month after the treatment ( P < .001 ) . The improvement of NDI and persons ' satisfaction were significantly better after TBS . Neck spine mobility in rotation movements tended to improve significantly better and the frons-knee distance improved more after TBS . One year later , both NDI and neck pain were significantly better after TBS than in reference groups . A significant improvement was reported by 40 % to 45.5 % of subjects in the PT and M groups and by 68.6 % in the TBS group . Bone setters ' ability to communicate and to interact with patients was evaluated significantly higher . In the TBS group , the number of sick days was minimal as was the use of painkillers during 1-year follow-up compared to that in the reference groups . CONCLUSIONS Traditional bone setting , which is a soft manual mobilization technique focusing on the muscles , joints , and ligaments , appears to be effective in cNP . Two thirds of subjects experienced it as beneficial Output:	Assessment of the clinical applicability of the trials showed that the participant characteristics were well reported , but neither the descriptions of the massage intervention nor the credentials or experience of the massage professionals were well reported . Therefore , the role of massage in multimodal treatments remains unclear .
MS22567	*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: Negative symptoms are considered the most debilitating and refractory aspect of schizophrenia , being associated with poor social , occupational and global outcomes . Conventional antipsychotics have limited efficacy against these symptoms and poor tolerability profiles . Atypical antipsychotics are an alternative treatment , and this 12‐week , r and omised , flexibly dosed study compared the efficacy , safety and tolerability of quetiapine and olanzapine in this regard . Of the 40 patients who entered the study ( 32 male ; 8 female ) , 19 were r and omised to quetiapine ( mean dose 637 mg/day , mean treatment duration 80 days ) and 21 to olanzapine ( mean dose 16 mg/day , mean treatment duration 78 days ) . Quetiapine and olanzapine were similarly effective : in each treatment group significant improvements at Week 12 were observed for negative symptom scores on the SANS and the PANSS , and for subscale scores of affective flattening and alogia on the SANS . Both treatments were well tolerated in this patient population , with no worsening of extrapyramidal symptoms in either case . Anxiety and insomnia were the most common adverse events ( ≥7 % of patients in each group ) , but were not drug‐related . Although this is a small study with limited power , the results support the effectiveness of quetiapine and olanzapine in treating the negative symptoms of schizophrenia . Copyright © 2006 John Wiley & Sons , BACKGROUND Amisulpride is a substituted benzamide with high selectivity for dopamine D2 and D3 receptors . The purpose of the study was to evaluate the effect of 100 mg amisulpride in patients with predominantly negative symptoms of schizophrenia . METHOD This was a multi-centre , r and omised , parallel-group , double-blind study . Patients received either amisulpride ( 100 mg/day ) or placebo over a six-month treatment period . RESULTS A total of 141 patients were included , 69 received amisulpride , 72 placebo . Fifty-eight patients ( 41 % ) had received neuroleptic treatment prior to inclusion . The percentage of amisulpride patients completing the study ( 55 % ) was significantly higher than that with placebo ( 32 % ) , and drop-out rates due to lack of efficacy were 27 % with amisulpride and 47 % with placebo . All efficacy assessment s were statistically in favour of amisulpride compared with placebo . The overall incidence of extrapyramidal symptoms was comparable in both groups ; only five patients started anti-Parkinsonian treatment during the study ( one in the placebo and four in the amisulpride group ) . CONCLUSION Amisulpride is effective in the medium-term treatment schizophrenic patients with predominantly negative symptoms Background The approximately 1100 medical journals now active in China are publishing a rapidly increasing number of research reports , including many studies identified by their authors as r and omized controlled trials . It has been noticed that these reports mostly present positive results , and their quality and authenticity have consequently been called into question . We investigated the adequacy of r and omization of clinical trials published in recent years in China to determine how many of them met acceptable st and ards for allocating participants to treatment groups . Methods The China National Knowledge Infrastructure electronic data base was search ed for reports of r and omized controlled trials on 20 common diseases published from January 1994 to June 2005 . From this sample , a subset of trials that appeared to have used r and omization methods was selected . Twenty-one investigators trained in the relevant knowledge , communication skills and quality control issues interviewed the original authors of these trials about the participant r and omization methods and related quality -control features of their trials . Results From an initial sample of 37,313 articles identified in the China National Knowledge Infrastructure data base , we found 3137 apparent r and omized controlled trials . Of these , 1452 were studies of conventional medicine ( published in 411 journals ) and 1685 were studies of traditional Chinese medicine ( published in 352 journals ) . Interviews with the authors of 2235 of these reports revealed that only 207 studies adhered to accepted methodology for r and omization and could on those grounds be deemed authentic r and omized controlled trials ( 6.8 % , 95 % confidence interval 5.9–7.7 ) . There was no statistically significant difference in the rate of authenticity between r and omized controlled trials of traditional interventions and those of conventional interventions . R and omized controlled trials conducted at hospitals affiliated to medical universities were more likely to be authentic than trials conducted at level 3 and level 2 hospitals ( relative risk 1.58 , 95 % confidence interval 1.18–2.13 , and relative risk 14.42 , 95 % confidence interval 9.40–22.10 , respectively ) . The likelihood of authenticity was higher in level 3 hospitals than in level 2 hospitals ( relative risk 9.32 , 95 % confidence interval 5.83–14.89 ) . All r and omized controlled trials of pre-market drug clinical trial were authentic by our criteria . Of the trials conducted at university-affiliated hospitals , 56.3 % were authentic ( 95 % confidence interval 32.0–81.0 ) . Conclusion Most reports of r and omized controlled trials published in some Chinese journals lacked an adequate description of r and omization . Similarly , most so called ' r and omized controlled trials ' were not real r and omized controlled trials owing toa lack of adequate underst and ing on the part of the authors of rigorous clinical trial design . All r and omized controlled trials of pre-market drug clinical trial included in this research were authentic . R and omized controlled trials conducted by authors in high level hospitals , especially in hospitals affiliated to medical universities had a higher rate of authenticity . That so many non-r and omized controlled trials were published as r and omized controlled trials reflected the fact that peer review needs to be improved and a good practice guide for peer review including how to identify the authenticity of the study urgently needs to be developed BACKGROUND Although predominant negative symptoms of schizophrenia can be severe enough to cause persistent impairment , effective treatment options are lacking . We aim ed to assess the new generation antipsychotic cariprazine in adult patients with predominant negative symptoms . METHODS In this r and omised , double-blind , phase 3b trial , we enrolled adults aged 18 - 65 years with long-term ( > 2 year ) , stable schizophrenia and predominant negative symptoms ( > 6 months ) at 66 study centres ( mainly hospitals and university clinics , with a small number of private practice s ) in 11 European countries . Patients were r and omly assigned ( 1:1 ) by an interactive web response system to 26 weeks of monotherapy with fixed-dose oral cariprazine ( 3 mg , 4·5 mg [ target dose ] , or 6 mg per day ) or risperidone ( 3 mg , 4 mg [ target dose ] , or 6 mg per day ) ; previous medication was discontinued over 2 weeks . The primary outcome was change from baseline to week 26 or end of treatment on the Positive and Negative Syndrome Scale factor score for negative symptoms ( PANSS-FSNS ) analysed in a modified intention-to-treat population of patients who had follow-up assessment s within 5 days after last receipt of study drugs with a mixed-effects model for repeated measures . Safety was assessed in all patients who received at least one dose of study drug . This study is registered with EudraCT , number 2012 - 005485 - 36 . FINDINGS Between May 27 , 2013 , and Nov 17 , 2014 , 533 patients were screened and 461 ( 86 % ) patients were r and omised to treatment ( 230 for cariprazine and 231 for risperidone ) ; 460 were included in the safety population ( one patient discontinued before study drug intake ) . 227 ( 99 % ) of 230 patients in the cariprazine group and 229 ( 99 % ) of 230 patients in the risperidone group were included in the modified intention-to-treat population ( 178 [ 77 % ] in each group completed 26 weeks of treatment ) . Mean daily doses were 4·2 mg ( SD 0·6 ) for cariprazine and 3·8 mg ( 0·4 ) for risperidone . Treatment-emergent adverse events ( eg , insomnia , akathisia , worsening of schizophrenia , headache , anxiety ) were reported in 123 ( 54 % ) patients treated with cariprazine and 131 ( 57 % ) patients treated with risperidone . Use of cariprazine led to a greater least squares mean change in PANSS-FSNS from baseline to week 26 than did risperidone ( -8·90 points for cariprazine vs -7·44 points for risperidone ; least squares mean difference -1·46 , 95 % CI -2·39 to -0·53 ; p=0·0022 ; effect size 0·31 ) . One patient in the risperidone group died of a cause regarded as unrelated to treatment . INTERPRETATION Our results support the efficacy of cariprazine in the treatment of predominant negative symptoms of schizophrenia . FUNDING Gedeon Richter Plc The study investigated the non-inferiority of flupentixol compared to risperidone in the treatment of negative symptoms . In addition , the effects of flupentixol on mood and cognitive symptoms were explored . In a r and omized , double-blind multicenter study , 144 non-acute schizophrenia patients with predominant negative symptoms were treated with a flexible dose of either flupentixol ( 4 - 12 mg/d ) or risperidone ( 2 - 6 mg/d ) for up to 25 weeks . In addition to a non-inferiority analysis , a principal component analysis ( PCA ) of the PANSS was performed post hoc . Regarding negative symptoms , flupentixol proved to be non-inferior to risperidone . Both drugs improved depressed mood with effect sizes favoring flupentixol . PCA suggested a five-factor structure . Effect sizes for the cognitive factor were up to 0.74 for flupentixol and up to 0.80 for risperidone . EPS scores were rather low and Parkinsonism improved in both groups , but anticholinergic drugs were prescribed significantly more frequently in the flupentixol group , which generally showed significantly more adverse events . Results indicate that the 1st generation antipsychotic flupentixol improves negative , affective and cognitive symptoms in chronic schizophrenia comparable to risperidone . Further studies should confirm the latter using neuropsychological performance tests and should investigate whether tolerability improves with a markedly lower dose range OBJECTIVE To discuss the quality of r and omized controlled trials ( RCTs ) in Chinese herbal medicine ( CHM ) with respect to design and methodology , and provide suggestions for further improvement in future clinical trials . METHODS A search of the Cochrane Library was conducted to identify RCTs of CHM on line in July 2005 . Quality of the RCTs was assessed using a 11-item checklist modified from the revised CONSORT statement , with 2 items specific to CHM ( i.e. herb preparation form and quality control of herbs ) . RESULTS The search yielded 167 RCTs that were selected for assessment . All trials included statements about the interventions , objectives , primary outcome design , statistical methods , and herb preparation form . Although 163 ( 97.6 % ) trials reported inclusion criteria , exclusion criteria were only reported in 26 ( 15.6 % ) trials . Fewer than 10 % of trials clearly stated the r and om allocation sequence generation methods , and only 2.4 % mentioned allocation concealment . The vast majority ( 86.8 % ) of trials were open-label , while only 13.2 % used blinding . Almost half ( 45.5 % ) administered the CHM intervention as a tea or decoction . Only one trial ( 0.6 % ) reported a sample size calculation , and a single trial ( 0.6 % ) discussed quality control of the CHM intervention . CONCLUSION The overall method ologic quality of RCTs in CHM was poor . It is essential to improve the design of future RCTs in this clinical area . RECOMMENDATIONS ( 1 ) Investigator conducting RCTs should have formal training about clinical trial design ; ( 2 ) A flow chart is recommended to ensure that all essential steps of clinical trial design are included . ( 3 ) Conducting pilot studies prior to RCTs may help improve their design ; ( 4 ) Registration of clinical trials and publishing their protocol s prior to enrollment may reduce publication bias and solicit peer review s of the proposed design ; ( 5 ) Collaboration between CHM investigators and traditional medicine academic research centers interested in integrative medicine may lead to quality improvement of RCTs of CHM BACKGROUND The efficacy of low doses of certain neuroleptics in improving negative symptoms is still controversial . This study assessed the efficacy of amisulpride , a benzamide which increases dopaminergic transmission at low doses via presynaptic dopamine receptor blockade , on negative symptoms of schizophrenia . METHOD The study was design ed as a parallel-group , double-blind , placebo-controlled trial . Patients had to fulfil DSM-III criteria for schizophrenia , And reasen 's criteria for negative schizop Output:	Overall , studies in prominent negative symptoms were potentially more confounded by improvements of secondary negative symptoms . InterpretationAmisulpride is the only antipsychotic that outperformed placebo in the treatment of predominant negative symptoms , but there was a parallel reduction of depression . Cariprazine was better than risperidone in a large trial that was well-controlled for secondary negative symptoms , but the trial was sponsored by its manufacturer .
MS22568	*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 authors investigated the use of slow-frequency repetitive transcranial magnetic stimulation ( rTMS ) to the unaffected hemisphere to decrease interhemispheric inhibition of the lesioned hemisphere and improve motor function in patients within 12 months of a stroke . Patients showed a significant decrease in simple and choice reaction time and improved performance of the Purdue Pegboard test with their affected h and after rTMS of the motor cortex in the intact hemisphere as compared with sham rTMS Objective : To investigate the long-term behavioral and neurophysiologic effects of combined time-locked repetitive transcranial magnetic stimulation ( rTMS ) and physical therapy ( PT ) intervention in chronic stroke patients with mild motor disabilities . Methods : Thirty patients were enrolled in a double-blind , r and omized , single-center clinical trial . Patients received 10 daily sessions of 1 Hz rTMS over the intact motor cortex . In different groups , stimulation was either real ( rTMSR ) or sham ( rTMSS ) and was administered either immediately before or after PT . Outcome measures included dexterity , force , interhemispheric inhibition , and corticospinal excitability and were assessed for 3 months after the end of treatment . Results : Treatment induced cumulative rebalance of excitability in the 2 hemispheres and a reduction of interhemispheric inhibition in the rTMSR groups . Use-dependent improvements were detected in all groups . Improvements in trained abilities were small and transitory in rTMSS patients . Greater behavioral and neurophysiologic outcomes were found after rTMSR , with the group receiving rTMSR before PT ( rTMSR-PT ) showing robust and stable improvements and the other group ( PT-rTMSR ) showing a slight improvement decline over time . Conclusion : Our findings indicate that priming PT with inhibitory rTMS is optimal to boost use-dependent plasticity and rebalance motor excitability and suggest that time-locked rTMS is a valid and promising approach for chronic stroke patients with mild motor impairment . Classification of evidence : This interventional study provides Class I evidence that time-locked rTMS before or after physical therapy improves measures of dexterity and force in the affected limb in patients with chronic deficits more than 6 months poststroke . Neurology ® Malcolm MP , Triggs WJ , Light KE , Gonzalez Rothi LJ , Wu S , Reid K , Nadeau SE : Repetitive transcranial magnetic stimulation as an adjunct to constraint-induced therapy : an exploratory r and omized controlled trial . Am J Phys Med Rehabil 2007;86:707–715 . Objective : To test the potential adjuvant effect of repetitive transcranial magnetic stimulation ( rTMS ) on motor learning in a group of stroke survivors undergoing constraint-induced therapy ( CIT ) for upper-limb hemiparesis . Design : This was a prospect i ve r and omized , double-blind , sham-controlled , parallel group study . Nineteen individuals , one or more years poststroke , were r and omized to either a rTMS + CIT ( n = 9 ) or a sham rTMS + CIT ( n = 10 ) group and participated in the 2-wk intervention . Results : Regardless of group assignment , participants demonstrated significant gains on the primary outcome measures : the Wolf Motor Function Test ( WMFT ) and the Motor Activity Log (MAL)–Amount of Use , and on secondary outcome measures including the Box and Block Test ( BBT ) and the MAL – How Well . Participants receiving rTMS failed to show differential improvement on either primary outcome measure . Conclusions : Although this study provided further evidence that even relatively brief sessions of CIT can have a substantial effect , it provided no support for adjuvant use of rTMS Low-frequency repetitive transcranial magnetic stimulation ( rTMS ) of the unaffected hemisphere can enhance function of the paretic h and in patients with mild motor impairment . Effects of low-frequency rTMS to the contralesional motor cortex at an early stage of mild to severe hemiparesis after stroke are unknown . In this pilot , r and omized , double-blind clinical trial we compared the effects of low-frequency rTMS or sham rTMS as add-on therapies to outpatient customary rehabilitation , in 30 patients within 5–45 days after ischemic stroke , and mild to severe h and paresis . The primary feasibility outcome was compliance with the interventions . The primary safety outcome was the proportion of intervention-related adverse events . Performance of the paretic h and in the Jebsen – Taylor test and pinch strength were secondary outcomes . Outcomes were assessed at baseline , after ten sessions of treatment administered over 2 weeks and at 1 month after end of treatment . Baseline clinical features were comparable across groups . For the primary feasibility outcome , compliance with treatment was 100 % in the active group and 94 % in the sham group . There were no serious intervention-related adverse events . There were significant improvements in performance in the Jebsen – Taylor test ( mean , 12.3 % 1 month after treatment ) and pinch force ( mean , 0.5 Newtons ) in the active group , but not in the sham group . Low-frequency rTMS to the contralesional motor cortex early after stroke is feasible , safe and potentially effective to improve function of the paretic h and , in patients with mild to severe hemiparesis . These promising results will be valuable to design larger r and omized clinical trials Background and Purpose — Although there has been extensive research on the effectiveness of repetitive transcranial magnetic stimulation ( rTMS ) to improve patients ’ motor performance after experiencing chronic stroke , explicit findings on the coupling of different rTMS protocol s are meager . We design ed this sham-controlled r and omized study to investigate the potential for a consecutive suppressive-facilitatory TMS protocol to improve motor outcomes after chronic stroke . Methods — Fifty-four chronic hemiplegic stroke patients were allocated across 4 groups to undergo 20 daily sessions of ( 1 ) 1 Hz rTMS over the contralesional primary motor cortex ( M1 ) and then intermittent theta burst stimulation over the ipsilesional M1 ( group A ) ; ( 2 ) contralesional sham stimulation and then ipsilesional real intermittent theta burst stimulation ( group B ) ; ( 3 ) contralesional real 1 Hz rTMS and then ipsilesional sham stimulation ( group C ) ; or ( 4 ) bilateral sham-control procedures ( group D ) . We tested cortical excitability and motor activity assessment s at the baseline , postpriming rTMS , and postconsequent rTMS periods . Results — At post , group A showed greater muscle strength , Fugl-Meyer Assessment ( FMA ) , Wolf Motor Function test , and reaction time improvement in comparison with group B ( P<0.001≈0.003 ) and group C ( P=0.001≈0.003 ) . Correlation analyses in group A revealed a close relation between contralesional map area decrement and Wolf Motor Function test gain ( P=0.005 ; r=−0.75 ) , and also revealed ipsilesional map area increment and reaction time decrement ( P=0.02 ; r=−0.87 ) . We detected no such relations in the other 3 groups . Conclusions — Our clinical trials established an extended timeframe during which conditioning could be safely continued and produced more favorable outcomes in facilitating motor performance and ameliorating interhemispheric imbalance than those obtained from single-course rTMS modulation alone Background and Purpose — It has been recently shown that a single session of repetitive transcranial magnetic stimulation ( rTMS ) of the unaffected hemisphere can improve motor function in stroke patients ; however , this improvement is short-lasting . We therefore conducted a r and omized , sham-controlled , phase II trial to evaluate whether five sessions of low-frequency rTMS can increase the magnitude and duration of these effects and whether this approach is safe . Methods — Fifteen patients with chronic stroke were r and omized to receive active or sham rTMS of the unaffected hemisphere . A blinded rater assessed motor function and corticospinal excitability at baseline , during and after 2 weeks of treatment . Safety was assessed using a neuropsychologic battery and electroencephalogram . Results — Active rTMS result ed in a significant improvement of the motor function performance in the affected h and that lasted for 2 weeks . These effects were not observed in the sham rTMS group ( affected and unaffected h and ) and in the unaffected h and in the active rTMS group . Corticospinal excitability decreased in the stimulated , unaffected hemisphere and increased in the affected hemisphere . There was a significant correlation between motor function improvement and corticospinal excitability change in the affected hemisphere . Cognitive performance and electroencephalogram were not changed significantly throughout the trial in both groups of treatment . Conclusions — These results support and extend the findings of previous studies on rTMS in stroke patients because five consecutive sessions of rTMS increased the magnitude and duration of the motor effects . Furthermore , this increased dose of rTMS is not associated with cognitive adverse effects and /or epileptogenic activity Background and Purpose — A recent report has demonstrated that the contralesional primary motor cortex ( M1 ) inhibited the ipsilesional M1 via an abnormal transcallosal inhibition ( TCI ) in stroke patients . We studied whether a decreased excitability of the contralesional M1 induced by 1 Hz repetitive transcranial magnetic stimulation ( rTMS ) caused an improved motor performance of the affected h and in stroke patients by releasing the TCI . Methods — We conducted a double-blind study of real versus sham rTMS in stroke patients . After patients had well- performed motor training to minimize the possibility of motor training during the motor measurement , they were r and omly assigned to receive a subthreshold rTMS at the contralesional M1 ( 1 Hz , 25 minutes ) or sham stimulation . Results — When compared with sham stimulation , rTMS reduced the amplitude of motor-evoked potentials in contralesional M1 and the TCI duration , and rTMS immediately induced an improvement in pinch acceleration of the affected h and , although a plateau in motor performance had been reached by the previous motor training . This improvement in motor function after rTMS was significantly correlated with a reduced TCI duration . Conclusions — We have demonstrated that a disruption of the TCI by the contralesional M1 virtual lesion caused a paradoxical functional facilitation of the affected h and in stroke patients ; this suggests a new neurorehabilitative strategy for stroke patients BACKGROUND AND PURPOSE Repetitive transcranial magnetic stimulation ( rTMS ) may enhance plastic changes in the human cortex and modulation of behavior . However , the underlying neural mechanisms have not been sufficiently investigated . We examined the clinical effects and neural correlates of high-frequency rTMS coupled with motor training in patients with hemiparesis after stroke . METHODS Twenty-one patients were r and omly divided into two groups , and received either real or sham rTMS . Ten daily sessions of 1,000 pulses of real or sham rTMS were applied at 10 Hz over the primary motor cortex of the affected hemisphere , coupled with sequential finger motor training of the paretic h and . Functional MRIs were obtained before and after training using sequential finger motor tasks , and performances were assessed . RESULTS Following rTMS intervention , movement accuracy of sequential finger motor tasks showed significantly greater improvement in the real group than in the sham group ( p < 0.05 ) . Real rTMS modulated areas of brain activation during performance of motor tasks with a significant interaction effect in the sensorimotor cortex , thalamus , and cau date nucleus . Patients in the real rTMS group also showed significantly enhanced activation in the affected hemisphere compared to the sham rTMS group . CONCLUSION According to these results , a 10 day course of high-frequency rTMS coupled with motor training improved motor performance through modulation of activities in the cortico-basal ganglia-thalamocortical circuits Repetitive transcranial magnetic stimulation of the motor cortex ( rTMS ) can be used to modify motor cortical excitability in human subjects . At stimulus intensities near to or above resting motor threshold , low-frequency rTMS ( approximately 1 Hz ) decreases motor cortical excitability , whereas high-frequency rTMS ( 5 - 20 Hz ) can increase excitability . We investigated the effect of 10 min of intermittent rTMS on motor cortical excitability in normal subjects at two frequencies ( 2 or 6 Hz ) . Three low intensities of stimulation ( 70 , 80 , and 90 % of active motor threshold ) and sham stimulation were used . The number of stimuli were matched between conditions . Motor cortical excitability was investigated by measurement of the motor-evoked potential ( MEP ) evoked by single magnetic stimuli in the relaxed first dorsal interosseus muscle . The intensity of the single stimuli was set to evoke baseline MEPs of approximately 1 mV in amplitude . Both 2- and 6-Hz stimulation , at 80 % of active motor threshold , reduced the magnitude of MEPs for approximately 30 min ( P < 0.05 ) . MEPs returned to baseline values after a weak voluntary contraction . Stimulation at 70 and 90 % of active motor threshold and sham stimulation did not induce a significant group effect on MEP magnitude . However , the intersubject response to rTMS at 90 % of active motor threshold was highly variable , with some subjects showing significant MEP facilitation and others inhibition . These results suggest that , at low stimulus intensities , the intensity of stimulation may be as important as frequency in determining the effect of rTMS on motor cortical excitability OBJECTIVE To investigate whether multiple sessions of 1-Hz repetitive transcranial magnetic stimulation ( rTMS ) facilitates the effect of repetitive facilitation exercises on hemiplegic upper-limb function in chronic stroke patients . DESIGN R and omized double-blinded crossover study . PATIENTS Eighteen patients with hemiplegia of the upper lim Output:	Conclusions : rTMS promoted the recovery of limb motor function and changed the cortex excitability . rTMS may be better for early and pure subcortical stroke patients . Regarding different stimulation parameters , the number of stimulation sessions has an impact on the effect of rTMS
MS22569	*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 OBJECTIVE To compare the clinical and oncologic outcomes of Robotic radical hysterectomy ( RRH ) vs Laparoscopic radical hysterectomy ( TLRH ) in patients with cervical carcinoma . DESIGN Long term follow-up in a prospect i ve study between March 2010 to March 2016 . SETTING Oncological referral center , department of gynecology and obstetrics of Aless and ro Manzoni Hospital , department of gynecology , University of San Gerardo Monza , Milan . PATIENTS 52 patients with cervical carcinoma , matched by age , body mass index , tumor size , International Federation of Gynecology and Obstetrics ( FIGO ) stage , comorbidity , previous neoadjuvant chemotherapy , histology type , and tumor grade to obtain homogeneous sample s. INTERVENTIONS Patients with FIGO stage IA2 or IB1 with a tumor size less than or equal to 2 cm underwent RR type B. RR-Type C1 was performed in stage IB1 , with a tumor size larger than 2 cm , or in patients previously treated with NACT ( IB2 ) . In all cases Pelvic lymphadenectomy was performed for the treatment of cervical cancer . MEASUREMENTS AND MAIN RESULTS Surgical time was similar for both the 2 groups . RRH was associated with significantly less ( EBL ) estimated blood loss ( P=0,000 ) . Median number pelvic lymph nodes was similar , but a major number of nodes was observed in RRH group ( 35.58 vs 24.23 ; P=0,050 ) . The overall median length of follow-up was 59 months ( range : 9 - 92 ) and 30 months ( range : 90 - 6 ) for RRH and TLRH group respectively . Overall survival rate ( OSR ) was 100 % for RRH group and 83.4 % for LTRH group . The DFS ( disease free survival rate ) was of 97 % and 89 % in RRH and LTRH group respectively . No significant difference was reported in HS ( hospital stay ) . CONCLUSIONS RRH is safe and feasible and is associated with an improved intraoperative results and clinical oncological outcomes . The present study showed that robotic surgery , in comparison to laparoscopic approach , was associated with better perioperative outcomes because of a decrease of EBL , and similar operative time , HS and complication rate , without neglecting the long-term optimal oncologic outcomes Objective The primary aim is to evaluate the surgical and oncological outcome of robotic radical hysterectomy ( RRH ) plus pelvic lymphadenectomy in locally advanced cervical cancer ( LACC ) after neoadjuvant chemotherapy ( NACT ) . The secondary aim is to compare the surgical and oncological results of RRH after NACT with a historical cohort of patients undergoing laparoscopic radical hysterectomy or abdominal radical hysterectomy plus pelvic lymphadenectomy for LACC after NACT . Methods We enrolled a total of 41 patients in this study with LACC undergoing RRH , who achieved a clinical partial or complete response to NACT . The surgical and oncological outcomes of 2 historical groups were compared : the laparoscopic group ( 41 patients ) with the laparotomic group ( 43 patients ) . Results The median estimated blood loss , operative time , and length of hospital stay were statistically significant and in favor of the robotic group . No conversion to laparotomy in the robotic group was necessary . There were no significant differences between the 3-year overall survival and disease-free survival rates in the minimally invasive groups ; nevertheless , the robotic group showed the same recurrence rate of laparoscopic in a short-interval follow-up . Conclusions The robotic approach could be considered a feasible and safe alternative to other surgical options . Multicenter r and omized clinical trials with longer follow-ups are necessary to evaluate the overall oncologic outcomes of this procedure OBJECTIVE Robotic surgery , with its technical advances , promises to open a new window to minimally invasive surgery in gynaecology . Feasibility and safety of this surgical innovation have been demonstrated in several studies , and now a critical analysis of these new developments regarding outcome and costs is in place . So far only a few studies compare robotic with conventional laparoscopic surgery in gynaecology . Our objective was to evaluate our initial experience performing total robot-assisted hysterectomy with the da Vinci surgical system and compare peri-operative outcome and costs with total laparoscopic hysterectomy . STUDY DESIGN For this prospect i ve matched case-control study at our institution , peri-operative data from our first 40 consecutive total robot-assisted hysterectomies for benign indications were recorded and matched 1:1 with total laparoscopic hysterectomies according to age , BMI and uterus weight . Surgical costs were calculated for both procedures . Surgeons ' subjective impressions of robotics were evaluated with a self-developed question naire . RESULTS No conversions to laparotomy or severe peri-operative complications occurred . Mean operating time was 109 ( 113 ; 50 - 170 ) min for the robotic group and 83 ( 80 ; 55 - 165 ) min for the conventional laparoscopic group . Mean postoperative hospitalisation for robotic surgery was 3.3 ( 3 ; 2 - 6 ) days versus 3.9 ( 4 ; 2 - 7 ) days for the conventional laparoscopic group . Average surgical cost of a robot-assisted laparoscopic hysterectomy was 4067 euros compared to 2151 euros for the conventional laparoscopic procedure at our institution . For the robotic group wider range of motion of the instruments and better ergonomics were considered to be an advantage , and lack of direct access to the patient was stated as a disadvantage . CONCLUSION Robot-assited hysterectomy is a feasible and interesting new technique with comparable outcome to total laparoscopic hysterectomy . Operating times of total laparoscopic hysterectomy seem to be achieved quickly especially for experienced laparoscopic surgeons . However , costs of robotic surgery are still higher than for conventional laparoscopy . R and omised clinical trials need to be conducted to further evaluate benefits of this new technology for patients and surgeons and analyse its cost-effectiveness in gynaecology Background Recently , as a complex integrating a number of modern high-tech means , robotic surgery system is a well-deserved revolutionary tool in globally minimally invasive surgical field . For the first time in China , the objective of this study was to evaluate the efficacy and safety outcomes of robotic radical hysterectomy ( RRH ) in Chinese older women with cervical cancer compared with laparoscopic radical hysterectomy ( LRH ) . Methods In this prospect i ve , r and omized and double-blinded study , 60 Chinese older women with cervical cancer were evenly divided to accept the RRH or LRH . Follow-up period lasted for 24 months . Results Median age for the entire cohort was 65 ( range : 61 - 69 ) years . There was no difference in International Federation of Gynecology and Obstetrics ( FIGO ) stages and cell types between two groups ( p > 0.05 for all ) . Uterine size , tumor size , vaginal length and numbers of left and right pelvic lymph nodes did not differ between two groups ( p > 0.05 for all ) . No difference was observed in numbers of left and right lymph node metastasis ( p > 0.05 for all ) . All patients had negative margins without conversion to laparotomy . There were significantly less postoperative complications in the RRH group than in the LRH group ( p < 0.05 ) . Shorter indwelling time of bladder and drain catheters was observed in the RRH group than in the LRH group ( p < 0.05 for all ) . Length of postoperative hospital stay in the RRH group was significantly shorter compared with that in the LRH group ( p < 0.05 ) . Patients in two groups similarly experienced the recurrence and death ( p > 0.05 for all ) . Conclusions This study demonstrated that RRH provided additional benefits for Chinese older women with cervical cancer because of less complications and faster recovery compared with LRH . Meanwhile , this study supported an equivalence of surgical qualities and survival outcomes of RRH to LRH . Robotics-assisted surgical method is effective , safe and feasible for Chinese older women with cervical cancer Background . Robotic surgery in gynaecological oncology is a rapidly developing field as it offers several technical advantages over conventional laparoscopy . An audit was performed on the outcome of robotic surgery during our learning curve and compared with recent well-established laparoscopic procedure data . Method . Following acquisition of the da Vinci Surgical System ( Intuitive Surgical , Inc. , Sunnyvale , California , USA ) , we prospect ively analysed all cases performed over the first six months by one experienced gynaecologist who had been appropriately trained and mentored . Data on age , BMI , pathology , surgery type , blood loss , morbidity , return to theatre , hospital stay , and readmission rate were collected and compared with a consecutive series over the preceding 6 months performed laparoscopically by the same team . Results . A comparison of two consecutive series was made . The mean age was somewhat different , 55 years in the robotic versus 69 years in the laparoscopic group , but obesity was a feature of both groups with a mean of BMI 29.3 versus 28.06 , respectively . This difference was not statistically significant ( P = 0.54 ) . Three subgroups of minimal access surgical procedures were performed : total hysterectomy and bilateral salpingooophorectomy ( TH + BSO ) , total hysterectomy and bilateral salpingooophorectomy plus bilateral pelvic lymphadenectomy ( TH + BSO + BPLND ) , and radical hysterectomy plus bilateral pelvic lymphadenectomy ( RH + BPLND ) . The mean time taken to perform surgery for TH + BSO was longer in the robotic group , 151.2 min compared to 126.3 min in the laparoscopic group . TH + BSO + BPLND surgical time was similar to 178.3 min in robotic group and 176.5 min in laparoscopic group . RH + BPLND surgical time was similar , 263.6 min ( robotic arm ) and 264.0 min ( laparoscopic arm ) . However , the numbers in this initial analysis were small especially in the last two subgroups and do not allow for statistical analysis . The rate of complications necessitating intervention ( Clavien-Dindo classification grade 2/3 ) was higher in the robotic arm ( 22.7 % ) compared to the laparoscopic approach ( 4.5 % ) . The readmission rate was higher in the robotic group ( 18.2 % ) compared to the laparoscopic group ( 4.5 % ) . The return to theatre in the robotic group was 18.2 % and 4.5 % in laparoscopic group . Uncomplicated robotic surgery hospital stay appeared to be shorter , 1.3 days compared to the uncomplicated laparoscopic group , 2.5 days . There was no conversion to the open procedure in either arm . Estimated blood loss in all cases was less than 100 mL in both groups . Conclusion . Robotic surgery is comparable to laparoscopic surgery in blood loss ; however , the hospital stay in uncomplicated cases appears to be longer in the laparoscopic arm . Surgical robotic time is equivalent to laparoscopic in complex cases but may be longer in cases not requiring lymph node dissection . The robotic surgery team learning curve may be associated with higher rate of morbidity . Further research on the benefits to the surgeon is needed to clarify the whole picture of this versatile novel surgical approach Background and Objectives : To compare intraoperative , pathologic and postoperative outcomes of robotic radical hysterectomy ( RRH ) to total laparoscopic radical hysterectomy ( TLRH ) in patients with early stage cervical carcinoma . Methods : We prospect ively analyzed cases of TLRH or RRH with pelvic lymphadenectomy performed for treatment of early cervical cancer between 2000 and 2008 . Results : Thirty patients underwent TLRH and pelvic lymph-adenectomy for cervical cancer from August 2000 to June 2006 . Thirteen patients underwent RRH and pelvic lymph-adenectomy for cervical cancer from April 2006 to January 2008 . There were no differences between groups for age , tumor histology , stage , lymphovascular space involvement or nodal status . No statistical differences were observed regarding operative time ( 323 vs 318 min ) , estimated blood loss ( 157 vs 200 mL ) , or hospital stay ( 2.7 vs 3.8 days ) . Mean pelvic lymph node count was similar in the two groups ( 25 vs 31 ) . None of the robotic or laparoscopic procedures required conversion to laparotomy . The differences in major operative and postoperative complications between the two groups were not significant . All patients in both groups are alive and free of disease at the time of last follow up . Conclusion : Based on our experience , robotic radical hysterectomy appears to be equivalent to total laparoscopic radical hysterectomy with respect to operative time , blood loss , hospital stay , and oncological outcome . We feel the intuitive nature of the robotic approach , magnification , dexterity , and flexibility combined with significant reduction in surgeon 's fatigue offered by the robotic system will allow more surgeons to use a minimally invasive approach to radical hysterectomy INTRODUCTION Comparison of perioperative outcomes and recurrence in patients undergoing primary Output:	Conclusion In our meta- analysis the rate of infectious complications associated with robotic-assisted hysterectomy was no different than that associated with conventional laparoscopic-assisted hysterectomy
MS22570	*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 study describes the results of a controlled clinical trial involving 44 7- to 14-year-old children with recurrent abdominal pain who were r and omly allocated to either cognitive-behavioral family intervention ( CBFI ) or st and ard pediatric care ( SPC ) . Both treatment conditions result ed in significant improvements on measures of pain intensity and pain behavior . However , the children receiving CBFI had a higher rate of complete elimination of pain , lower levels of relapse at 6- and 12-month follow-up , and lower levels of interference with their activities as a result of pain and parents reported a higher level of satisfaction with the treatment than children receiving SPC . After controlling for pretreatment levels of pain , children 's active self-coping and mothers ' caregiving strategies were significant independent predictors of pain behavior at posttreatment The symptoms of 72 patients with irritable bowel syndrome were assessed by question naire before and 6 months after a high-fibre diet had been prescribed , to find whether those who achieved the highest fibre intake did any better than those with smaller intakes . Dietary fibre intakes were measured after 6 months by a 7-day weighed food inventory . There was a significant inverse association between the presence of symptoms and fibre intake for : incomplete defaecation , urgency and hard stools with total fibre intake ; urgency and hard stools with cereal fibre intake ; and borborygmi with fibre intake at breakfast . All patients with constipation , mucus , urgency or watery stools at the beginning of the study , and who were consuming more than 30 g fibre by the end , reported an improvement in these symptoms . Increasing intakes of fibre were not related in any way to abdominal distension , diarrhoea , flatulence or patient 's feelings about the working of their bowels . Therefore , this study suggests that the symptoms which benefit most from the prescription of a high-fibre diet are hard stools , constipation and urgency A number of recent clinical trials have promoted the use of probiotic bacteria as a treatment for irritable bowel syndrome ( IBS ) . The recent demonstration of abnormal colonic fermentation in some patients with this condition provides an opportunity for the objective assessment of the therapeutic value of these bacteria . This study was design ed to investigate the effects of Lactobacillus plantarum 299V on colonic fermentation . We conducted a double-blind , placebo-controlled , cross-over , four-week trial of Lactobacillus plantarum 299V in 12 previously untreated patients with IBS . Symptoms were assessed daily by a vali date d composite score and fermentation by 24-hr indirect calorimetry in a 1.4-m3 canopy followed by breath hydrogen determination for 3 hr after 20 ml of lactulose . On placebo , the median symptom score was 8.5 [ 6.25–11.25 interquartile range ( IQR ) ] , the median maximum rate of gas production was 0.55 ml/min ( 0.4–1.1 IQR ) , and the median hydrogen production was 189.7 ml/24 hr ( 118.3–291.1 IQR ) . On Lactobacillus plantarum 299V the median symptom score was 8 ( 6.75–13.5 IQR ) , the median maximum rate of gas production 0.92 ml/min ( 0.45–1.5 IQR ) , and the median hydrogen production 208.2 ml/24 hr ( 146–350.9 IQR ) . There was no significant difference . Breath hydrogen excretion after lactulose was reduced by the probiotic ( median at 120 min , 6 ppm ; placebo , 17 ppm ; P = 0.019 ) . In conclusion , Lactobacillus plantarum 299V in this study did not appear to alter colonic fermentation or improve symptoms in patients with the irritable bowel syndrome Objectives Recurrent abdominal pain ( RAP ) is a common childhood complaint rarely associated with organic disease . Recently , the Pediatric Rome Criteria were developed to st and ardize the classification of pediatric functional gastrointestinal disorders ( FGIDs ) using a symptom-based approach . The authors tested the hypothesis that most patients with childhood RAP could be classified into one or more of the symptom subtypes defined by the Pediatric Rome Criteria . Methods Using a prospect i ve longitudinal design , new patients with RAP ( n = 114 ) were studied at a tertiary care children 's medical center . Before the medical evaluation , parents completed a question naire about their child , assessing symptoms defined by the Pediatric Rome Criteria . Results Of the 107 children for whom medical evaluation revealed no organic etiology for pain , 73 % had symptom profiles consistent with the Pediatric Rome Criteria for one of the FGIDs associated with abdominal pain ( irritable bowel syndrome , 44.9 % ; functional dyspepsia,15.9 % ; functional abdominal pain , 7.5 % ; abdominal migraine , 4.7 % ) Conclusions This study provides the first systematic empirical evidence that RAP , originally defined by Apley , includes children whose symptoms are consistent with the symptom criteria for several FGIDs defined by the Rome criteria . The pediatric Rome criteria may be useful in clinical research to ( 1 ) describe the symptom characteristics of research participants who meet Apley 's broad criteria for RAP , and ( 2 ) select patients with particular symptom profiles for investigation of potential biologic and psychosocial mechanisms associated with pediatric FGIDs OBJECTIVE To assess whether parental psychological and physical factors and child factors measured in the first year of life were associated with recurrent abdominal pain ( RAP ) in children at age 6(3/4 ) years . METHOD A longitudinal cohort study ( the Avon Longitudinal Study of Parents and Children ) , followed 8,272 children from pregnancy to age 6(3/4 ) years . Parental reports of child and parent functioning were gathered . Associations between parental and child functioning assessed at 6 to 8 months postpartum , and RAP measured at age 6(3/4 ) years were investigated . RESULTS The prevalence of RAP in this sample was 11.8 % . Both maternal anxiety ( adjusted odds ratio = 1.53 ; 95 % confidence interval 1.24 - 1.89 ) and paternal anxiety ( adjusted odds ratio = 1.38 ; 95 % confidence interval 1.12 - 1.71 ) in the first year of a child 's life were associated with later childhood RAP . Parent reports of child temperament features such as irregular feeding and sleeping were also associated with later RAP . CONCLUSIONS This is the first evidence from a prospect i ve study that anxiety in both mothers and fathers and child temperament features pre date the occurrence of RAP in children . These findings highlight the potential importance of addressing parental anxiety in families in which children present with RAP , although some caution should be exercised in their interpretation because of possible reporting bias We sought to prospect ively characterize and compare the symptoms of children ≥ 5 years of age with recurrent abdominal pain to previously established criteria for irritable bowel syndrome ( IBS ) in adults . For all eligible subjects , a detailed question naire concerning characteristics of abdominal pain and defecatory pattern was completed at presentation . In addition , a battery of screening tests was performed and additional evaluation was done at the discretion of their physician . In all , 227 subjects fulfilled the entrance criteria , but 56 were sub-sequently excluded because of diagnoses of inflammatory bowel disease ( nine cases ) , lactose malabsorption ( 46 cases ) , or celiac disease ( one case ) . Of the remaining 171 patients , 117 had IBS symptoms . In the IBS subjects , lower abdominal discomfort ( p < 0.001 ) , cramping pain ( p < 0.0009 ) , and increased flatus ( p < 0.0003 ) were more common , whereas dyspeptic symptoms such as epigastric discomfort ( p < 0.003 ) , pain radiating to the chest ( p < 0.009 ) , and regurgitation ( p < 0.02 ) were more common in the non-IBS subjects . Our study not only confirms the clinical heterogeneity of children with recurrent abdominal pain but also concomitantly demonstrates that most children with this disorder have symptoms that fulfill the st and ardized criteria for IBS in adults . The identification of subgroups of children with recurrent abdominal pain can provide a framework for the diagnosis of functional bowel disease as well as establish the need for invasive and expensive tests OBJECTIVE : The influence of the gastrointestinal ( GI ) microflora in patients with irritable bowel syndrome ( IBS ) has not been clearly eluci date d. This study was undertaken to see if patients with IBS have an imbalance in their normal colonic flora , as some bacterial taxa are more prone to gas production than others . We also wanted to study whether the flora could be altered by exogenous supplementation . In a previous study we have characterized the mucosa-associated lactobacilli in healthy individuals and found some strains with good colonizing ability . Upon colonization , they seemed to reduce gas formation . METHODS : The study comprised 60 patients with IBS and a normal colonoscopy or barium enema . Patients fulfilling the Rome criteria , without a history of malabsorption , and with normal blood tests underwent a sigmoidoscopy with biopsy . They were r and omized into two groups , one receiving 400 ml per day of a rose-hip drink containing 5 × 107 cfu/ml of Lactobacillus plantarum ( DSM 9843 ) and 0.009 g/ml oat flour , and the other group receiving a plain rose-hip drink , comparable in color , texture , and taste . The administration lasted for 4 wk . The patients recorded their own GI function , starting 2 wk before the study and continuing throughout the study period . Twelve months after the end of the study all patients were asked to complete the same question naire regarding their symptomatology as at the start of the study . RESULTS : All patients tolerated the products well . The patients receiving Lb . plantarum had these bacteria on rectal biopsies . There were no major changes of Enterobacteriaceae in either group , before or after the study , but the Enterococci increased in the placebo group and remained unchanged in the test group . Flatulence was rapidly and significantly reduced in the test group compared with the placebo group ( number of days with abundant gas production , test group 6.5 before , 3.1 after vs 7.4 before and 5.6 after for the placebo group ) . Abdominal pain was reduced in both groups . At the 12-month follow-up , patients in the test group maintained a better overall GI function than control patients . There was no difference between the groups regarding bloating . Fifty-nine percent of the test group patients had a continuous intake of fermented products , whereas the corresponding figure for the control patients was 73 % . CONCLUSIONS : The results of the study indicate that the administration of Lb . plantarum with known probiotic properties decreased pain and flatulence in patients with IBS . The fiber content of the test solution was minimal and it is unlikely that the fiber content could have had any effect . This type of probiotic therapy warrants further studies in IBS patients The prevalence of psychological problems was investigated in 44 children with abdominal pain of organic origin ( Crohn 's disease , 24 ; ulcerative colitis , 20 ) , 16 children with non-organic abdominal pain , and 30 pain-free controls . A self-report battery of five tests was used to measure personal , family , and social adjustment . Compared with controls , all three abdominal-pain groups showed psychological problems . Of significance were depression and low self-esteem in patients with Crohn 's disease , depression in those with ulcerative colitis , and low self-esteem in those with non-organic pain . No differences were found between patients with organic and those with non-organic pain . These findings indicate that psychological distress accompanies both organic and non-organic abdominal pain in children and that psychological evaluation may not readily distinguish organic from non-organic cases Output:	This review provides no evidence that fibre supplements , lactose free diets or lactobacillus supplementation are effective in the management of children with RAP
MS22571	*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 Advances in technology allowed the development of a novel smoking cessation program delivered by video messages sent to mobile phones . This social cognitive theory-based intervention ( called “ STUB IT ” ) used observational learning via short video diary messages from role models going through the quitting process to teach behavioral change techniques . Objective The objective of our study was to assess the effectiveness of a multimedia mobile phone intervention for smoking cessation . Methods A r and omized controlled trial was conducted with 6-month follow-up . Participants had to be 16 years of age or over , be current daily smokers , be ready to quit , and have a video message-capable phone . Recruitment targeted younger adults predominantly through radio and online advertising . Registration and data collection were completed online , prompted by text messages . The intervention group received an automated package of video and text messages over 6 months that was tailored to self-selected quit date , role model , and timing of messages . Extra messages were available on dem and to beat cravings and address lapses . The control group also set a quit date and received a general health video message sent to their phone every 2 weeks . Results The target sample size was not achieved due to difficulty recruiting young adult quitters . Of the 226 r and omized participants , 47 % ( 107/226 ) were female and 24 % ( 54/226 ) were Maori ( indigenous population of New Zeal and ) . Their mean age was 27 years ( SD 8.7 ) , and there was a high level of nicotine addiction . Continuous abstinence at 6 months was 26.4 % ( 29/110 ) in the intervention group and 27.6 % ( 32/116 ) in the control group ( P = .8 ) . Feedback from participants indicated that the support provided by the video role models was important and appreciated . Conclusions This study was not able to demonstrate a statistically significant effect of the complex video messaging mobile phone intervention compared with simple general health video messages via mobile phone . However , there was sufficient positive feedback about the ease of use of this novel intervention , and the support obtained by observing the role model video messages , to warrant further investigation . Trial registration Australian New Zeal and Clinical Trials Registry Number : ACTRN12606000476538 ; http://www.anzctr.org.au/trial_view.aspx?ID=81688 ( Archived by WebCite at http://www.webcitation.org/5umMU4sZi Background Smoking is more prevalent among lower-income individuals and certain racial/ethnic minorities . Addressing tobacco cessation among diverse population s is an urgent public health priority . As Internet use continues to rise among all segments of the US population , Web-based interventions have enormous potential to reach priority population s. Conducting Web-based smoking cessation research in priority population s requires psychometrically sound measurement instruments . To date , only one published study has examined the psychometric properties of Internet-administered measures commonly used in Web-based cessation trials . However , the sample was homogeneous with regard to race/ethnicity and income . We sought to replicate and extend these findings in a more diverse sample of smokers . Objective The aim was to examine the internal consistency and test-retest reliability of measures commonly used in smoking cessation clinical trials among racial/ethnic minorities and smokers with lower income . Methods Participants were enrolled in a r and omized trial of the efficacy of an Internet smoking cessation program between June 2005 and September 2006 . Following a baseline telephone assessment and r and omization into the parent trial , participants were recruited to the reliability sub study . In phase I of recruitment , all participants in the parent trial were recruited to the sub study ; in phase II , all consecutive racial/ethnic minority participants in the parent trial were recruited . Race and ethnicity were assessed via self-report using two st and ard items from the US Office of Management and Budget . An email was sent 2 days after the telephone assessment with a link to the Internet survey . Measures examined were quit methods , perceived stress , depression , social support , smoking temptations , alcohol use , perceived health status , and income . Internal consistency and test-retest reliability of Internet- versus telephone-administered measures were examined within four strata defined by race/ethnicity ( non-Hispanic White , racial/ethnic minority ) and annual household income ( US $ 40,000 or less , more than $ 40,000 ) . Results Of the 442 individuals invited , 319 participated ( 72 % response rate ) : 52.4 % were non-Hispanic White , 22.9 % Black , 11.6 % Hispanic , 7.8 % Asian , 4.4 % American Indian / Alaska Native , and 1 % Native Hawaiian / Other Pacific Isl and er . About half ( 49.4 % ) reported an annual household income of US $ 40,000 or less , and 25.7 % had a high school degree or less . Test-retest reliability was satisfactory to excellent across all strata for the majority of measures examined : 9 of 12 continuous variables had intraclass correlation coefficients ≥ 0.70 , and 10 of 18 binary variables and both ordinal variables had kappa coefficients ≥ 0.70 . Test-retest reliability of several quit methods varied across strata . Conclusions Race/ethnicity and income do not affect the psychometric properties of most Internet-administered measures examined . This knowledge adds to the confidence of conducting Web-based smoking cessation research and strengthens the scientific rigor of collecting information via the Internet on racial/ethnic minority and low-income subgroups . Trial registration clinical trials.gov NCT00282009 ( parent trial OBJECTIVES To examine patterns of nicotine dependence , the value of the Fagerström Test for Nicotine Dependence ( FTND ) and its correlation with self-reported tobacco use and urinary cotinine concentrations among pregnant Indigenous women in Townsville . DESIGN , PARTICIPANTS AND SETTING Cross-sectional study of 201 consecutive women who self-reported tobacco use at their first antenatal visit to Townsville Aboriginal and Isl and er Health Service ( TAIHS ) between 1 November 2005 and 31 October 2007 . All smokers were to be assessed by FTND , and 108 women participating in the Tilly 's Tracks project ( a r and omised trial of an intervention to reduce smoking in pregnant Aboriginal and Torres Strait Isl and er women ) were to have a comprehensive smoking history taken and urinary cotinine sample s collected . MAIN OUTCOME MEASURES Self-reported smoking status , FTND scores and urinary cotinine concentrations . RESULTS Of 302 Indigenous women presenting to TAIHS , 201 ( 66.6 % ) identified as current tobacco users at their first antenatal visit ; this proportion rose to 79.6 % in women aged<20 years . An FTND was completed for 152 women ( 75.6 % ) , with a median score of 4 , and 40.1 % scoring 3 or less , indicating low levels of nicotine dependence . There were significant correlations between the FTND and number of cigarettes smoked ( r=0.56 ; P<0.001 ) and urinary cotinine concentrations ( r=0.25 ; P=0.030 ) . Of those who provided comprehensive smoking histories , the median age of starting smoking was 15 years , with a median of two previous quit attempts ; 71.4 % reported partners who smoked and 27.3 % reported smoking occurred inside the house . CONCLUSION The use of the FTND in Indigenous pregnant women may assess physical nicotine dependence , thus providing information that will help in preparing quit-smoking plans , including tailoring of pharmacological support to individual need . Quit-smoking programs that better address the behavioural and psychological aspects of smoking within the Indigenous community in Australia are needed We present statistical considerations for the design of the Community Intervention Trial for Smoking Cessation ( COMMIT ) . One outcome measurement , the quit rate in r and omly selected cohorts of smokers , is compared with another outcome measurement , the decrease in smoking prevalence , in terms of statistical efficiency and interpretability . The COMMIT study uses both types of outcome measurements . The merits of pair-matching the communities are considered , and sample size calculations take into account heterogeneity among pair-matched communities . In addition to significance tests based on the permutational ( r and omization ) distribution , we also describe approaches for covariate adjustment . The COMMIT design includes 11 pair-matched communities , which should provide good power to detect a 10 % or greater difference in quit rates between the intervention and control communities in cohorts of heavy smokers and in cohorts of light or moderate smokers . The power is only moderate to detect intervention effects on the decreases in overall smoking prevalence or in the prevalence of heavy smoking Background : Smoking rates are high in indigenous population s and contribute to their poor health . In New Zeal and the indigenous Maori population has a high rate of smoking , with around 50 % of adults being smokers compared with 20 % of the adult European population . A study was undertaken to determine whether bupropion is effective in the treatment of smoking cessation in the indigenous Maori population in New Zeal and . Methods : A r and omised , placebo controlled , double blind , parallel group study was performed in 134 Maori smokers aged 16–70 years who smoked more than 10 cigarettes per day . The main outcome measures were continued abstinence from smoking at 3 and 12 months . Results : At each time point continued abstinence was better for the subjects allocated to bupropion , with a risk ratio for abstinence over all time points of 2.44 ( 95 % CI 1.22 to 4.88 ) . The rates of continued abstinence in the bupropion and placebo groups at 3 months were 44.3 % and 17.4 % , respectively , with a risk ratio of 2.54 ( 95 % CI 1.30 to 5.00 ) . The corresponding figures at 12 months were 21.6 % and 10.9 % , respectively , with a risk ratio of 1.99 ( 95 % CI 0.79 to 5.00 ) . Conclusion : Bupropion is an effective treatment for smoking cessation in the indigenous Maori population in New Zeal and Objectives : To determine the effectiveness of a mobile phone text messaging smoking cessation programme . Design : R and omised controlled trial Setting : New Zeal and Participants : 1705 smokers from throughout New Zeal and who wanted to quit , were aged over 15 years , and owned a mobile phone were r and omised to an intervention group that received regular , personalised text messages providing smoking cessation advice , support , and distraction , or to a control group . All participants received a free month of text messaging ; starting for the intervention group on their quit day to assist with quitting , and starting for the control group at six months to encourage follow up . Follow up data were available for 1624 ( 95 % ) at six weeks and 1265 ( 74 % ) at six months . Main outcome measures : The main trial outcome was current non-smoking ( that is , not smoking in the past week ) six weeks after r and omisation . Secondary outcomes included current non-smoking at 12 and 26 weeks . Results : More participants had quit at six weeks in the intervention compared to the control group : 239 ( 28 % ) v 109 ( 13 % ) , relative risk 2.20 ( 95 % confidence interval 1.79 to 2.70 ) , p < 0.0001 . This treatment effect was consistent across subgroups defined by age , sex , income level , or geographic location ( p homogeneity > 0.2 ) . The relative risk estimates were similar in sensitivity analyses adjusting for missing data and salivary cotinine verification tests . Reported quit rates remained high at six months , but there was some uncertainty about between group differences because of incomplete follow up . Conclusions : This programme offers potential for a new way to help young smokers to quit , being affordable , personalised , age appropriate , and not location dependent . Future research should test these findings in different setting s , and provide further assessment of long term quit rates Background Acute respiratory illness ( ARI ) is the most common cause of acute presentations and hospitalisations of young Indigenous children in Australia and New Zeal and ( NZ ) . Environmental tobacco smoke ( ETS ) from household smoking is a significant and preventable contributor to childhood ARI . This paper describes the protocol for a study which aims to test the efficacy of a family-centred tobacco control program about ETS to improve the respiratory health of Indigenous infants in Australia and New Zeal and . For the purpose of this paper ' Indigenous ' refers to Australia 's Aboriginal and Torres Strait Isl and er peoples when referring to Australian Indigenous population s. In New Zeal and , the term ' Indigenous ' refers to Māori . Methods / Design This study will be a parallel , r and omized , controlled trial . Participants will be Indigenous women and their infants , half of whom will be r and omly allocated to an ' intervention ' group , who will receive the tobacco control program over three home visits in the first three months of the infant 's life and half to a control group receiving ' usual care ' ( i.e. they will not receive the tobacco control program ) . Indigenous health workers will deliver the intervention , the goal of which is to reduce or eliminate infant exposure to ETS . Data collection will occur at baseline ( shortly after birth ) and when the infant is four months and one year of age . The primary outcome is a doctor-diagnosed , documented case of respiratory illness in participating infants . Discussion Interventions aim ed at reducing exposure of Indigenous children to ETS have the potential for significant benefits for Indigenous communities . There Output:	The limited but available evidence reported does indicate that smoking cessation interventions specifically targeted at Indigenous population s can produce smoking abstinence .
MS22572	*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 Primary pulmonary hypertension is a progressive disease for which no treatment has been shown in a prospect i ve , r and omized trial to improve survival . METHODS We conducted a 12-week prospect i ve , r and omized , multicenter open trial comparing the effects of the continuous intravenous infusion of epoprostenol ( formerly called prostacyclin ) plus conventional therapy with those of conventional therapy alone in 81 patients with severe primary pulmonary hypertension ( New York Heart Association functional class III or IV ) . RESULTS Exercise capacity was improved in the 41 patients treated with epoprostenol ( median distance walked in six minutes , 362 m at 12 weeks vs. 315 m at base line ) , but it decreased in the 40 patients treated with conventional therapy alone ( 204 m at 12 weeks vs. 270 m at base line ; P < 0.002 for the comparison of the treatment groups ) . Indexes of the quality of life were improved only in the epoprostenol group ( P < 0.01 ) . Hemodynamics improved at 12 weeks in the epoprostenol-treated patients . The changes in mean pulmonary-artery pressure for the epoprostenol and control groups were -8 percent and + 3 percent , respectively ( difference in mean change , -6.7 mm Hg ; 95 percent confidence interval , -10.7 to -2.6 mm Hg ; P < 0.002 ) , and the mean changes in pulmonary vascular resistance for the epoprostenol and control groups were -21 percent and + 9 percent , respectively ( difference in mean change , -4.9 mm Hg/liter/min ; 95 percent confidence interval , -7.6 to -2.3 mm Hg/liter/min ; P < 0.001 ) . Eight patients died during the study , all of whom had been r and omly assigned to conventional therapy ( P = 0.003 ) . Serious complications included four episodes of catheter-related sepsis and one thrombotic event . CONCLUSIONS As compared with conventional therapy , the continuous intravenous infusion of epoprostenol produced symptomatic and hemodynamic improvement , as well as improved survival in patients with severe primary pulmonary hypertension BACKGROUND Pulmonary arterial hypertension with systemic dysfunctions , including metabolic disorders and renal dysfunction , has a poor prognosis . However , it remains to be eluci date d whether chronic thromboembolic pulmonary hypertension ( CTEPH ) is also associated with systemic dysfunctions , and if so , whether balloon pulmonary angioplasty ( BPA ) improves them . METHODS AND RESULTS Fifty-five consecutive patients who underwent BPA from March 2012 to December 2014 for systemic dysfunctions , including glycemic control , lipid profiles , renal and vascular function , and nutritional status were examined . The analyses were performed before and after BPA ( mean , 3.5 sessions/patient ) and changes in hemodynamic parameters were compared . The average follow-up period was 474±245 days . Baseline prevalence of hypertension , diabetes mellitus , dyslipidemia and advanced chronic kidney disease was 58 , 7 , 33 and 36 % , respectively . BPA caused marked hemodynamic improvements in the CTEPH patients . Importantly , BPA also significantly improved dysglycemia ( fasting blood sugar , hemoglobin A1c and homeostatic assessment model of insulin resistance ) , renal ( creatinine and estimated glomerular filtration rate ) and vascular ( cardio-ankle vascular index ) functions and nutritional status ( albumin , cholesterols , and body mass index ) . Importantly , there were positive correlations between the degrees of the hemodynamic improvements and those of other improvements . CONCLUSIONS These results indicate that BPA may exert multiple beneficial effects in CTEPH patients , not only in terms of hemodynamics but also in other systemic functions , with positive correlations among them Background — Pulmonary hypertension caused by systolic left ventricular dysfunction is associated with significant morbidity and mortality ; however , no treatment is approved for this indication . We hypothesized that riociguat , a novel soluble guanylate cyclase stimulator , would have beneficial hemodynamic effects in patients with pulmonary hypertension caused by systolic left ventricular dysfunction . Methods and Results — Overall , 201 patients with heart failure result ing from pulmonary hypertension caused by systolic left ventricular dysfunction were r and omized to double-blind treatment with oral placebo or riociguat ( 0.5 , 1 , or 2 mg 3 times daily ) for 16 weeks in 4 parallel arms . The primary outcome was the placebo-corrected change from baseline at week 16 in mean pulmonary artery pressure . Although the decrease in mean pulmonary artery pressure in the riociguat 2 mg group ( −6.1±1.3 mm Hg ; P<0.0001 versus baseline ) was not significantly different from placebo ( P=0.10 ) , cardiac index ( 0.4 L·min−1·m−2 ; 95 % confidence interval , 0.2–0.5 ; P=0.0001 ) and stroke volume index ( 5.2 mL·m−2 ; 95 % confidence interval , 2.0–8.4 ; P=0.0018 ) were significantly increased without changes in heart rate or systemic blood pressure compared with placebo . Both pulmonary ( −46.6 dynes·s−1·cm−5 ; 95 % confidence interval , –89.4 to –3.8 ; P=0.03 ) and systemic vascular resistance ( −239.3 dynes·s−1·cm−5 ; 95 % confidence interval , –363.4 to –115.3 ; P=0.0002 ) were significantly reduced with riociguat 2 mg . Riociguat reduced the Minnesota Living With Heart Failure score ( P=0.0002 ) . Discontinuation of treatment was similar between treatment groups . Conclusions — Although the primary end point of the study was not met , riociguat was well tolerated in patients with pulmonary hypertension caused by systolic left ventricular dysfunction and improved cardiac index and pulmonary and systemic vascular resistance . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01065454 The aim of the present study was to determine contemporary survival in pulmonary arterial hypertension ( PAH ) , and to investigate whether or not the National Institutes of Health ( NIH ) equation remains an accurate predictor of survival . In 576 patients with PAH referred during 1991–2007 , observed survival was described using the Kaplan – Meier method . In patients with idiopathic , familial and anorexigen-associated PAH ( n = 247 ) , observed versus NIH equation predicted survival was compared . A new survival prediction equation was developed using exponential regression analysis . The observed 1- , 3- and 5-yr survival in the total cohort were 86 , 69 and 61 % , respectively . In patients with idiopathic , familial and anorexigen-associated PAH , the observed 1- , 3- and 5-yr survival ( 92 , 75 and 66 % , respectively ) were significantly higher than the predicted survival ( 65 , 43 and 32 % , respectively ) . The new equation ( P(t ) = e-A(x , y , z)t , where P(t ) is probability of survival , t the time interval in years , A(x , y , z ) = e(−1.270–0.0148x+0.0402y–0.361z ) , x the mean pulmonary artery pressure , y the mean right atrial pressure and z the cardiac index ) performed well when applied to published contemporary studies of survival in PAH . Contemporary survival in the PAH cohort was better than that predicted by the NIH registry equation . The NIH equation underestimated survival in idiopathic , familial and anorexigen-associated PAH . Once prospect ively vali date d , the new equation may be used to determine prognosis We assessed the therapeutic potential of riociguat , a novel soluble guanylate cyclase stimulator , in adults with chronic thromboembolic pulmonary hypertension ( CTEPH ; n = 42 ) or pulmonary arterial hypertension ( PAH ; n = 33 ) in World Health Organization ( WHO ) functional class II/III . In this 12-week , multicentre , open-label , uncontrolled phase II study , patients received oral riociguat 1.0–2.5 mg t.i.d . titrated according to systemic systolic blood pressure ( SBP ) . Primary end-points were safety and tolerability ; pharmacodynamic changes were secondary end-points . Riociguat was generally well tolerated . Asymptomatic hypotension ( SBP < 90 mmHg ) occurred in 11 patients , but blood pressure normalised without dose alteration in nine and after dose reduction in two . Median 6-min walking distance increased in patients with CTEPH ( 55.0 m from baseline ( 390 m ) ; p<0.0001 ) and PAH ( 57.0 m from baseline ( 337 m ) ; p<0.0001 ) ; patients in functional class II or III and bosentan pre-treated patients showed similar improvements . Pulmonary vascular resistance was significantly reduced by 215 dyn·s·cm−5 from baseline ( 709 dyn·s·cm−5 ; p<0.0001 ) . 42 ( 56 % ) patients were considered to have experienced drug-related adverse events ( AEs ; 96 % mild or moderate ) . Dyspepsia , headache and hypotension were the most frequent AEs . Study discontinuation because of AEs was 4 % . These preliminary data show that riociguat has a favourable safety profile and improves exercise capacity , symptoms and pulmonary haemodynamics in CTEPH and PAH . R and omised controlled trials are underway PATENT PLUS evaluated the safety and efficacy of riociguat in combination with sildenafil in pulmonary arterial hypertension patients . Patients receiving sildenafil ( 20 mg three times daily ) were r and omised to placebo or riociguat ( up to 2.5 mg three times daily ) for 12 weeks . The primary outcome was maximum change in supine systolic blood pressure ( SBP ) from baseline within 4 h of dosing . Secondary objectives comprised additional blood pressure , heart rate and exploratory efficacy variables , and safety . Patients could enter a long-term extension ( LTE ) , where all patients received riociguat plus sildenafil . There was no difference in maximum change in supine SBP from baseline within 4 h between the riociguat ( n=12 ) ( mean±sd baseline : –20.2±15.3 mmHg ; week 12 : –20.7±18.0 mmHg ) and placebo groups ( n=6 ) ( –7.6±3.9 and –20.2±12.9 mmHg , respectively ) . Changes in st and ing SBP and supine or st and ing diastolic blood pressure were also not different . Combination therapy showed no favourable effects on exploratory clinical parameters , including haemodynamics and exercise capacity . In the LTE , there were high rates of discontinuation due to hypotension and three ( 18 % ) deaths ( not considered study drug-related by the investigator ) . There were potentially unfavourable safety signals with sildenafil plus riociguat and no evidence of a positive benefit/risk ratio . Concomitant use of riociguat with phosphodiesterase-5 inhibitors is therefore contraindicated . Sildenafil+riociguat in PAH : no evidence of a positive benefit/risk ratio and potentially unfavourable safety signals We assessed the safety , tolerability and preliminary efficacy of riociguat , a soluble guanylate cyclase stimulator , in patients with pulmonary hypertension associated with interstitial lung disease ( PH-ILD ) . In this open-label , uncontrolled pilot trial , patients received oral riociguat ( 1.0–2.5 mg three times daily ) for 12 weeks ( n=22 ) , followed by an ongoing long-term extension ( interim analysis at 12 months ) in those eligible ( n=15 ) . Primary end-points were safety and tolerability . Secondary end-points included haemodynamic changes and 6-min walk distance ( 6MWD ) . Overall , 104 adverse events were reported , of which 25 were serious ; eight of the latter were considered drug-related . After 12 weeks of therapy , mean cardiac output increased ( 4.4±1.5 L·min−1 to 5.5±1.8 L·min−1 ) , pulmonary vascular resistance ( PVR ) decreased ( 648±207 dyn·s−1·cm−5 to 528±181 dyn·s−1·cm−5 ) and mean pulmonary artery pressure ( mPAP ) remained unchanged compared with baseline . Arterial oxygen saturation decreased but mixed-venous oxygen saturation slightly increased . The 6MWD increased from 325±96 m at baseline to 351±111 m after 12 weeks . Riociguat was well tolerated by most patients and improved cardiac output and PVR , but not mPAP . Further studies are necessary to evaluate the safety and efficacy of riociguat in patients with PH-ILD Riociguat ( BAY 63 - 2521 ) and war Output:	sGC stimulators improve pulmonary artery pressures in people with PAH ( who are treatment naive or receiving a prostanoid or endothelin antagonist ) or those with recurrent or inoperable CTEPH . In these setting s this can be achieved without notable complication . However , sGC stimulators should not be taken by people also receiving phosphodiestase-V inhibitors or nitrates due to the risks of hypotension , and there is currently no evidence supporting their use in pulmonary hypertension associated with left heart disease . There is no evidence supporting their use in children .
MS22573	*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: Obese subjects with impaired glucose tolerance ( IGT ) are more susceptible than healthy individuals to oxidative stress and cardiovascular disease . This r and omised controlled investigation was design ed to test the hypothesis that α-lipoic acid supplementation and exercise training may elicit favourable clinical changes in obese subjects with IGT . All data were collected from 24 obese ( BMI ≥ 30 kg/m2 ) IGT patients . Following participant r and omisation into two groups , fasting venous blood sample s were obtained at baseline , and before and following intervention . The first group consisted of 12 participants who completed a 12 week control phase followed by 12 weeks of chronic exercise at 65 % HRmax for 30 minutes a day , 5 days per week , while ingesting 1 gram per day of α-lipoic acid for 12 weeks . The second group consisted of 12 participants who completed the same 12 week control phase , but this was followed by 12 weeks of 1 gram per day of α-lipoic acid supplementation only ( no exercise ) . The main findings show a comparatively greater rate of low density lipoprotein ( LDL ) oxidation in the group consisting of α-lipoic acid only ( p < 0.05 vs. pre intervention ) , although total oxidant status was lower post intervention ( p < 0.05 vs. baseline ) in this group . However , exercise and α-lipoic acid in combination attenuates LDL oxidation . Furthermore , in the α-lipoic acid supplement plus exercise training group , total antioxidant capacity was significantly increased ( p < 0.05 vs. baseline and pre intervention ) . Body fat percentage and waist and hip circumference decreased following exercise training ( p < 0.05 vs. post intervention ) . There were no selective treatment differences for a range of other clinical outcomes including glycaemic regulation ( p > 0.05 ) . These findings report that α-lipoic acid ingestion may increase the atherogenicity of LDL when ingested in isolation of exercise , suggesting that in IGT the use of this antioxidant treatment does not ameliorate metabolic disturbances , but instead may detrimentally contribute to the pathogenesis of atherosclerosis and development of CVD . However , when α-lipoic acid is combined with exercise , this atherogenic effect is abolished Objectives : To evaluate the effect of ubiquinone and combined antioxidant therapy on mitochondrial function in non-proliferative diabetic retinopathy ( NPDR ) in a r and omized , double-blind , phase IIa , placebo-controlled , clinical trial . Three groups of 20 patients were formed : Group 1 , ubiquinone ; Group 2 , combined therapy ; and Group 3 , placebo ( one daily dose for 6 months ) . Methods : Fluidity of the su bmi tochondrial membrane in platelets was determined by examining intensity of fluorescence between the monomer ( I m ) and excimer ( Ie ) . Hydrolytic activity of the mitochondrial F0F1-ATPase was evaluated with the spectrophotometric method . Results : Normal , baseline su bmi tochondrial membrane fluidity , 0.24 ± 0.01 Ie/Im , was significantly diminished in the three study groups vs. normal values ( P < 0.0001 ) ; placebo , 0.14 ± 0.01 Ie/Im ; ubiquinone , 0.14 ± 0.01 Ie/Im ; and combined therapy , 0.13 ± 0.00 Ie/Im . Afterward , it increased significantly ( P < 0.0001 ) , the ubiquinone group 0.22 ± 0.01 Ie/Im , combined therapy group , 0.19 ± 0.01 Ie/Im ; with no changes the placebo group . Baseline hydrolytic activity of the F0F1-ATPase enzyme increased in the three study groups vs. normal values ( 184.50 ± 7.84 nmol PO4 ) , placebo , 304.12 ± 22.83 nmol PO4 ( P < 0.002 ) ; ubiquinone , 312.41 ± 25.63 nmol PO4 ( P < 0.009 ) ; and combined therapy , 371.28 ± 33.50 nmol PO4 ( P < 0.002 ) . Afterward , a significant decrease the enzymatic activity : ubiquinone , 213.25 ± 14.19 nmol PO4 ( P < 0.001 ) ; and combined therapy , 225.55 ± 14.48 nmol PO4 ( P < 0.0001 ) . Discussion : Mitochondrial dysfunction significantly improved in groups of NPDR patients treated with antioxidants Objective To evaluate the effect of ubiquinone ( Coenzyme Q10 ) and combined antioxidant therapy ( CAT ) on oxidative stress markers in non-proliferative diabetic retinopathy ( NPDR ) under clinical management . Study design In a r and omized , double-blind , phase IIa , placebo-controlled , clinical trial , three study groups were formed and administered medications as follows : Group 1 , Coenzyme Q10 ; Group 2 , CAT ; and Group 3 , placebo . Methods Serum levels of the products of lipid peroxidation ( LPO ) and nitrites/nitrates , as markers of oxidative/nitrosative stress , were measured . As antioxidants , the total antioxidant capacity ( TAC ) , catalase activity , and glutathione peroxidase ( GPx ) activity were measured . Results Baseline serum levels of LPO and nitrites/nitrates were significantly elevated in the three groups vs. healthy group ( P < 0.0001 ) , while final levels in the Coenzyme Q10 and CAT groups were decreased vs. normal levels ( P < 0.0001 ) . The baseline TAC was consumed in the three groups ( P < 0.0001 ) , while final results in the Coenzyme Q10 and CAT groups improved ( P < 0.0001 ) . Baseline catalase activity was increased in all groups vs. normal values ( P < 0.001 ) , while final levels in the Coenzyme Q10 ( P < 0.001 ) and CAT groups ( P < 0.0001 ) were decreased . GPx behaved similarly to catalase and improved in the final results ( P < 0.0001 ) . Discussion Adjunctive antioxidant treatment for 6 months was effective and safe for improving the oxidative stress in NPDR Aims : The aim was to evaluate circulating levels of reactive oxygen species ( ROS ) and changes in central macular thickness ( CMT ) in patients with nonproliferative diabetic retinopathy ( NPDR ) after antioxidant supplementation . Material s and Methods : A total of 68 patients ( 68 eyes ) with NPDR were enrolled . Patients were r and omly divided into two groups : Treated with antioxidant supplement ( Group A ) and untreated control group ( Group B ) . Each tablet , for oral administration , containing pycnogenol 50 mg , Vitamin E 30 mg and coenzyme Q10 20 mg . CMT and free oxygen radical test ( FORT ) were analyzed at baseline ( T0 ) , 3 ( T1 ) and 6 ( T2 ) months in both groups . Results : In Group A , FORT levels and CMT were significantly reduced over time ( P < 0.001 for both ) . In Group B , FORT levels were increased ( P < 0.001 ) and CMT did not vary significantly ( P = 0.81 ) over 3 time points . Conclusions : This is the first study showing the reduction of ROS levels in patients with NPDR thanks to antioxidant therapy . Moreover , our findings have suggested also an influence on retinal thickness Background Dealing with heterogeneity in meta-analyses is often tricky , and there is only limited advice for authors on what to do . We investigated how authors addressed different degrees of heterogeneity , in particular whether they used a fixed effect model , which assumes that all the included studies are estimating the same true effect , or a r and om effects model where this is not assumed . Methods We sample d r and omly 60 Cochrane review s from 2008 , which presented a result in its first meta- analysis with substantial heterogeneity ( I2 greater than 50 % , i.e. more than 50 % of the variation is due to heterogeneity rather than chance ) . We extracted information on choice of statistical model , how the authors had h and led the heterogeneity , and assessed the method ological quality of the review s in relation to this . Results The distribution of heterogeneity was rather uniform in the whole I2 interval , 50 - 100 % . A fixed effect model was used in 33 review s ( 55 % ) , but there was no correlation between I2 and choice of model ( P = 0.79 ) . We considered that 20 review s ( 33 % ) , 16 of which had used a fixed effect model , had major problems . The most common problems were : use of a fixed effect model and lack of rationale for choice of that model , lack of comment on even severe heterogeneity and of reservations and explanations of its likely causes . The problematic review s had significantly fewer included trials than other review s ( 4.3 vs. 8.0 , P = 0.024 ) . The problems became less pronounced with time , as those review s that were most recently up date d more often used a r and om effects model . Conclusion One-third of Cochrane review s with substantial heterogeneity had major problems in relation to their h and ling of heterogeneity . More attention is needed to this issue , as the problems we identified can be essential for the conclusions of the review Statins are potent cholesterol-lowering drugs and are generally well tolerated . Hepatotoxicity is a rare but serious adverse effect of statins ; however , its mechanisms are not clear . Coenzyme Q10 deficiency has been suggested , and supplementation of reduced coenzyme Q10 ( ubiquinol ) has been shown to have hepatoprotective effects . MicroRNAs ( miRNAs ) are small nucleotides that have been shown to be up-regulated in drug-induced liver injury . We hypothesized that circulating miRNAs may be differentially regulated after simvastatin treatment and by comparing with that of simvastatin and ubiquinol supplementation could potentially uncover signatory miRNA profile for simvastatin-induced liver injury . In this double-blind , prospect i ve , r and omized-controlled trial , miRNA profiles and liver enzymes were compared between simvastatin-treated patients , with and without ubiquinol supplementation , over 12 weeks compared to baseline . miRNA expression was further vali date d in HepG2 liver cell lines by real-time PCR . Changes in miR-192 , miR-146a , miR-148a , miR-15a , and miR-21 were positively correlated ( p<0.05 ) with alanine aminotransferase in simvastatin-only treated patients . In ubiquinol supplementation group , alanine aminotransferase and alkaline phosphatase were significantly down-regulated after 12 weeks and changes in miR-15a , miR-21 and miR-33a were negatively correlated with alkaline phosphatase ( p < 0.05 ) . Bioinformatics analyses predicted that miRNA regulation in simvastatin group was related to reduce proliferation and adenosine triphosphate-binding cassette transporters . Ubiquinol supplementation additionally regulated miRNAs that inhibit apoptotic and inflammatory pathways , suggesting potential hepatoprotective effects . Our results suggest that 20 mg/day of simvastatin does not have significant risk of hepatotoxicity and ubiquinol supplementation may , at the miRNA level , provide potential beneficial changes to reduce the effects of coenzyme Q10 deficiency in the liver Background : Adipolin , the novel adipokine that is proposed to be reduced in diabetes , obesity and inflammation , may improve glycemic control . It is known that coenzyme Q10 could improve insulin sensitivity . The aim of the current study was to investigate the effect of Q10 supplementation on adipolin concentration and glucose metabolism in overweight and obese diabetic patients . Material & Methods : Sixty four patients with type 2 diabetes and 25 < BMI < 35 kg/m2 were r and omly divided to receive 200 mg Q10 or placebo daily for 12 weeks . Fasting serum levels of adipolin , glucose , insulin , HbA1c and HOMA-IR were measured before and after supplementation . Results : Following supplementation , adipolin levels decreased significantly in Q10 group ( 38.19±32.02 to 29.03±34.23 ng/ml;P=0.001 ) . HbA1c decreased dramatically following supplementation only in Q10 group ( 8.6±2.2 % to 7.9±2.1 % , P<0.001 ) . It was also marginally lower in Q10 compared to placebo group at the end of study ( P=0.056 ) . Moreover , weight ( P=0.003 ) , BMI ( P=0.003 ) and waist circumference ( P=0.016 ) decreased significantly in Q10 group . No significant alterations were observed in FBS , fasting insulin and HOMA-IR within or between Q10 and placebo groups . Conclus Output:	Conclusions The overall results demonstrated that supplementation with CoQ10 shows an enhanced potential to lower CVD risk in diabetic patients by reducing total cholesterol and LDL . Moreover , the beneficial effects of CoQ10 in lowering the CVD risk are associated with its ameliorative properties against oxidative stress and improving endothelial health
MS22574	*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 determine the degree of interinstitutional transfusion practice variation and reasons why red cells are administered in critically ill patients . Study design Multicentre cohort study combined with a cross-sectional survey of physicians requesting red cell transfusions for patients in the cohort . Study population The cohort included 5298 consecutive patients admitted to six tertiary level intensive care units in addition to administering a survey to 223 physicians requesting red cell transfusions in these units . Measurements Haemoglobin concentrations were collected , along with the number and reasons for red cell transfusions plus demographic , diagnostic , disease severity ( APACHE II score ) , intensive care unit ( ICU ) mortality and lengths of stay in the ICU . Results Twenty five per cent of the critically ill patients in the cohort study received red cell transfusions . The overall number of transfusions per patient-day in the ICU averaged 0.95 ± 1.39 and ranged from 0.82 ± 1.69 to 1.08 ± 1.27 between institutions ( P < 0.001 ) . Independent predictors of transfusion thresholds ( pre-transfusion haemoglobin concentrations ) included patient age , admission APACHE II score and the institution ( P < 0.0001 ) . A very significant institution effect ( P < 0.0001 ) persisted even after multivariate adjustments for age , APACHE II score and within four diagnostic categories ( cardiovascular disease , respiratory failure , major surgery and trauma ) ( P < 0.0001 ) . The evaluation of transfusion practice using the bedside survey documented that 35 % ( 202 of 576 ) of pre-transfusion haemoglobin concentrations were in the range of 95 - 105 g/l and 80 % of the orders were for two packed cell units . The most frequent reasons for administering red cells were acute bleeding ( 35 % ) and the augmentation of O2 delivery ( 25 % ) . Conclusions There is significant institutional variation in critical care transfusion practice , many intensivists adhering to a 100g/l threshold , and opting to administer multiple units despite published guidelines to the contrary . There is a need for prospect i ve studies to define optimal practice in the critically ill OBJECTIVES We sought to determine the relationship between red blood cell ( RBC ) transfusion and clinical outcomes in patients undergoing primary percutaneous coronary intervention ( PCI ) for acute myocardial infa rct ion ( AMI ) . BACKGROUND The implication s of RBC transfusion in patients undergoing primary PCI for AMI have not been evaluated . METHODS Clinical outcomes of patients from the prospect i ve , r and omized CADILLAC ( Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications ) trial were analyzed by administration of in-hospital RBC transfusion not related to coronary artery bypass surgery . RESULTS Of 2,060 r and omized patients , 82 ( 3.98 % ) received RBC transfusion during the index hospitalization , including 33 ( 1.60 % ) with moderate/severe bleeding and 49 ( 2.38 % ) without overt major bleeding . Transfusion was independently associated with baseline anemia ( odds ratio [ 95 % confidence interval ] : 4.44 [ 2.60 to 7.58 ] , p < 0.0001 ) , older age ( 1.03 [ 1.01 to 1.06 ] , p = 0.002 ) , triple-vessel disease ( 2.54 [ 1.47 to 4.38 ] , p = 0.0008 ) , and female sex ( 1.04 [ 1.02 to 1.06 ] , p = 0.0008 ) . Patients transfused versus not transfused had significantly higher rates of 1-year mortality ( 23.9 % vs. 3.4 % ) , disabling stroke ( 2.5 % vs. 0.5 % ) , reinfa rct ion ( 7.0 % vs. 2.2 % ) , and composite major adverse cardiac events ( 41.0 % vs. 16.6 % ) ( all p values < 0.01 ) . After multivariable adjustment for potential confounders including transfusion propensity , RBC transfusion was independently associated with mortality at 30 days ( hazards ratio : 4.71 , p = 0.0005 ) and 1 year ( hazards ratio : 3.16 , p = 0.0005 ) . CONCLUSIONS An RBC transfusion after primary PCI in AMI may be harmful , which is consistent with the findings from other studies after PCI in the noninfa rct setting . Alternatively , RBC transfusion may be a marker of markedly increased risk . R and omized studies are warranted to determine the optimal threshold for RBC transfusion in patients with AMI undergoing mechanical reperfusion therapy Background : The long‐term prognostic implication of post‐procedural hematocrit drops in patients undergoing cardiac catheterization outside the clinical trial setting is not well defined . Methods : Data was prospect ively collected from 12,661 patients undergoing diagnostic or interventional cardiac catheterization between July 1998 and July 2006 . Patients were divided into three cohorts based upon the degree of hematocrit change : drop greater than 6 , drop between 3 and 6 , and drop less than 3 . In‐hospital major adverse events , 30‐day mortality , and long‐term all‐cause mortality were recorded . Results : Patients with larger reductions in hematocrit were more likely to be older , female , and have a higher baseline hematocrit , present with acute myocardial infa rct ion , develop cardiogenic shock , require emergent catheterization , develop retroperitoneal bleeds and large hematomas , receive transfusions , have longer index hospitalizations , develop subacute stent thrombosis , and have higher 30‐day and long‐term mortality . An increase in long‐term mortality was observed with progressive hematocrit drop . This finding is largely driven by early ( 30 day ) mortality , as trends were no longer significant after rezeroing mortality . Hematocrit drop was not an independent risk factor for 30‐day mortality . Transfusion and low baseline hematocrit were identified as independent predictors of near and long‐term mortality . Conclusions : Periprocedural bleeding , defined by hematocrit drop , is associated with increased near‐term and long‐term mortality in patients undergoing diagnostic and therapeutic cardiac catheterization procedures . Long‐term mortality is largely driven by up front 30‐day mortality . Hematocrit drop was not an independent predictor for near‐term mortality . Transfusion and low baseline hematocrit were independent predictors for near and long‐term mortality . © 2009 Wiley‐Liss , The relation across anemia , hemorrhagic complications , and mortality associated with percutaneous coronary intervention ( PCI ) is unclear . We review ed the R and omized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 Trial , which compared bivalirudin plus provisional glycoprotein IIb/IIIa blockade with heparin plus planned glycoprotein IIb/IIIa blockade in patients undergoing urgent or elective PCI . Of the 6,010 patients r and omized in REPLACE-2 , 1,371 ( 23 % ) were anemic . Major bleeding was more common in anemic than in nonanemic patients ( 4.9 % vs 2.8 % , p = 0.0001 ) . In anemic patients , treatment with bivalirudin ( n = 678 ) result ed in a lower risk of major bleeding versus heparin plus glycoprotein IIb/IIIa blockade ( n = 693 , 3.5 % vs 6.2 % , p = 0.0221 ) . Mortality was higher in anemic patients than in nonanemic patients at 30 days ( 0.9 % vs 0.2 % , p < 0.0001 ) , 6 months ( 2.6 % vs 0.7 % , p < 0.0001 ) , and 1 year ( 4.3 % vs 1.5 % , p < 0.0001 ) . There were no differences between anemic and nonanemic patients with regard to ischemic complications at 30 days . Although anemic patients had higher mortality rates , proportions of cardiovascular and noncardiovascular mortalities were equal in anemic and nonanemic patients . In conclusion , anemic patients undergoing PCI have an increased risk of mortality and major bleeding , but not of ischemic events , and the use of bivalirudin with provisional glycoprotein IIb/IIIa blockade decreases the risk of hemorrhagic complications compared with heparin plus planned glycoprotein IIb/IIIa blockade Background : Bleeding and transfusion after percutaneous coronary intervention ( PCI ) are known predictors of mortality . Transradial arterial access reduces bleeding and transfusion related to femoral access complications , although its association with mortality is unknown . Objective : To determine the association of arterial access site ( radial or femoral ) with transfusion and mortality in unselected PCIs . Design , setting and patients : By data linkage of three prospect ively collated provincial registries , 38 872 procedures in 32 822 patients in British Columbia were analysed . The association between access site , transfusion and outcomes was assessed by logistic regression , propensity score matching and probit regression . Main outcome measures : 30-Day and 1-year mortality . Results : 1134 ( 3.5 % ) patients had at least one blood transfusion . Transfused patients had a significantly increased 30-day and 1-year mortality , adjusted odds ratio ( 95 % CI ) 4.01 ( 3.08 to 5.22 ) and 3.58 ( 2.94 to 4.36 ) , respectively . By probit regression the absolute increase in risk of death at 1 year associated with receiving a transfusion was 6.78 % . The number needed to treat was 14.74 ( prevention of 15 transfusions required to “ avoid ” one death ) . Radial access halved the transfusion rate . After adjustment for all variables , radial access was associated with a significant reduction in 30-day and 1-year mortality , odds ratio = 0.71 ( 95 % CI 0.61 to 0.82 ) and 0.83 ( 0.71 to 0.98 ) , respectively ( all p<0.001 ) . Conclusions : In a registry of all comers to PCI , transradial access was associated with a halving of the transfusion rate and a reduction in 30-day and 1-year mortality BACKGROUND Prior trials suggest it is safe to defer transfusion at hemoglobin levels above 7 to 8 g/dL in most patients . Patients with acute coronary syndrome may benefit from higher hemoglobin levels . METHODS We performed a pilot trial in 110 patients with acute coronary syndrome or stable angina undergoing cardiac catheterization and a hemoglobin < 10 g/dL. Patients in the liberal transfusion strategy received one or more units of blood to raise the hemoglobin level ≥10 g/dL. Patients in the restrictive transfusion strategy were permitted to receive blood for symptoms from anemia or for a hemoglobin < 8 g/dL. The predefined primary outcome was the composite of death , myocardial infa rct ion , or unscheduled revascularization 30 days post r and omization . RESULTS Baseline characteristics were similar between groups except age ( liberal , 67.3 ; restrictive , 74.3 ) . The mean number of units transfused was 1.6 in the liberal group and 0.6 in the restrictive group . The primary outcome occurred in 6 patients ( 10.9 % ) in the liberal group and 14 ( 25.5 % ) in the restrictive group ( risk difference = 15.0 % ; 95 % confidence interval of difference 0.7 % to 29.3 % ; P = .054 and adjusted for age P = .076 ) . Death at 30 days was less frequent in liberal group ( n = 1 , 1.8 % ) compared to restrictive group ( n = 7 , 13.0 % ; P = .032 ) . CONCLUSIONS The liberal transfusion strategy was associated with a trend for fewer major cardiac events and deaths than a more restrictive strategy . These results support the feasibility of and the need for a definitive trial IMPORTANCE Studies have shown variation in the use of red blood cell transfusion among patients with acute coronary syndromes . There are no definitive data for the efficacy of transfusion in improving outcomes , and concerning data exist about possible association with harm . Current transfusion practice s in patients undergoing percutaneous coronary intervention ( PCI ) are not well understood . OBJECTIVE To determine the current patterns of blood transfusion among patients undergoing PCI and the association of transfusion with adverse cardiac outcomes across hospitals in the United States . DESIGN , SETTING , AND PARTICIPANTS Retrospective cohort study of all patient visits from the CathPCI Registry from July 2009 to March 2013 that included PCI , excluding those with missing data on bleeding complications or who underwent in-hospital coronary artery bypass graft surgery ( N = 2,258,711 visits ) . MAIN OUTCOMES AND MEASURES Trans Output:	Blood transfusion is independently associated with increased risk of mortality and MACE events .
MS22575	*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 A system-wide , multi-ethnicity study on Crohn 's disease ( CD ) of the pouch , including Indian American ( IA ) patients has not been conducted . AIM To compare the frequency of subsequent development of CD of the pouch for African-American ( AA ) , Hispanic-American ( HA ) , IA and Caucasian patients with ulcerative ( UC ) undergoing ileal-pouch anal anastomosis ( IPAA ) . METHODS In this historical cohort study from our Pouch Registry , patients with restorative proctocolectomy and IPAA for IBD with identifiable , self-declared racial background ( i.e. AA , HA , IA or Caucasian ) were included . Univariable and multivariable analyses were performed to identify risk factors for CD of the pouch . RESULTS The study included 235 patients : AA ( N=26 ) , HA ( N=37 ) , IA ( N=22 ) and r and omly selected Caucasian ( N=150 ) controls . Greater number of HA and Caucasians had a history of smoking than IA ( 27.3 % and 27.0 % vs. 0 ; p=0.007 ) . Caucasians and HA were also more likely to have a family history of IBD than IA or AA ( 25 % vs. 27 % vs. 5 % vs. 4 % ; p=0.016 . ) IA less frequently had extensive colitis before colectomy than Caucasians ( 71.4 % vs. 94.0 % ; p=0.004 ) and more frequently required anti-TNF biologics than HA ( 22.7 % vs. 0 ; p=0.016 ) . On multivariable logistic regression analysis , AA ( odds ratio [OR]=10.1 , 95 % confidence interval [ CI ] : 1.03 , 1365.8 , p=0.004 ) and Caucasians ( OR=11.1 , 95 % CI : 1.4 , 1427.2 , p=0.015 ) had a higher risk of developing CD of the pouch than IA . However , the event-free survival was not significantly different between the groups on Cox regression analysis , presumably due to the sample size . CONCLUSION Racial background may be associated with different risk for the development of CD of the pouch for patients with IBD undergoing IPAA PURPOSE Common belief based on clinical experience suggests that Crohn ’s disease is more severe among black patients , although little data exists on the effect of race on Crohn ’s disease . We compared multiple variables among black patients with Crohn ’s disease requiring surgery to those of white patients presenting to a university colorectal surgery unit during a five-year period . METHODS A total of 345 patients required surgery for Crohn ’s disease between June 1998 and September 2003 . The following data were abstract ed from patient charts and a prospect ively maintained data base : age at diagnosis ; age at first Crohn ’s disease surgery ; presenting symptoms ; incidence , number and location of fistulas at presentation ; number of Crohn ’s disease operations ; and family history of inflammatory bowel disease . Data regarding medical insurance coverage also were obtained . Complete data were evaluable on 178 patients . Patient variables were analyzed using the chi-squared , Fisher exact , and Student t-tests . RESULTS Mean age at diagnosis was 28 years for white males , 20 years for black males , 30 years for white females , and 28 years for black females ( all p > 0.05 ) . Thirty-seven percent of white females presented with obstructive symptoms vs. 12 percent of black females . ( P = 0.011 ) . Sixty-five percent of black females presented with inflammatory symptoms compared with 28 percent of white females ( P = 0.001 ) . Of females presenting with fistulas , 15 percent of black patients had a rectovaginal fistula compared with 5 percent of white patients . Seventeen percent of black males and 21 percent of white males had intra-abdominal fistulas . None of these differences were statistically significant . The incidence of fistulas at presentation , mean number of fistulas , total number of operations , and family history of inflammatory bowel disease did not differ . CONCLUSIONS Contrary to expectations , Crohn ’s disease does not seem to be more severe among black patients , who had an earlier age of diagnosis , although this was not statistically significant . Overall , there was no difference in disease presentation . White females were more likely to present with obstructive symptoms compared with black females , who more often presented with inflammatory symptoms . Among patients with fistulas , the incidence of rectovaginal fistulas was higher in black females compared with white females , and white males were somewhat more likely to have intra-abdominal fistulas than black males . Although there was no demonstrated difference in incidence and mean number of fistulas at presentation , the number of operations for Crohn ’s disease , or family history of inflammatory bowel disease among blacks and whites , there are differences in presenting symptoms among these population Background : Inflammatory bowel disease ( IBD ) is increasingly diagnosed in ethnic and racial minorities . Ileal pouch – anal anastomosis ( IPAA ) has become the treatment of choice for ulcerative colitis ( UC ) patients requiring surgery . Few studies have characterized the natural history of IPAA and the pouch outcomes in the Hispanic American population . Methods : Ethnicity was design ated by self‐report and the Hispanics who had IPAA for UC were identified from a prospect ively maintained data base . Demographics , clinical characteristics , and pouch outcomes were compared between Hispanic and a sample of Non‐Hispanic whites ( 1:4 ratio ) r and omly selected from the same data base . Exclusion criteria were patients with a preoperative diagnosis of Crohn 's disease or familial adenomatous polyposis , and patients of other ethnic groups . Results : Thirty‐six Hispanics with IPAA were identified . Hispanic patients were younger at UC diagnosis 23.1 ± 13.1 vs. 30.4 ± 12.6 yrs and at colectomy 31.9 ± 13.9 vs. 38.8 ± 13.8 yrs than controls . The interval between diagnosis and colectomy was comparable between the two groups . There were more uninsured in the Hispanic group than controls ( 13.9 % vs. 2.8 % ) . There were no significant differences in gender distribution , family history of IBD , smoking history , extent of UC , fulminant colitis , pouch configuration , stage of pouch , presence of extraintestinal manifestations , or concurrent autoimmune disorders . Pouch‐related disorders and pouch failure were also similar . Conclusions : There appeared to be some difference in the preoperative characteristics of patients who underwent colectomy for UC between Hispanics and non‐Hispanic whites , but outcomes after the restorative proctocolectomy with IPAA were comparable . Further studies are needed to characterize the natural history of UC and IPAA in the Hispanic population and the associated biosocioeconomic factors . ( Inflamm Bowel Dis 2011 ; OBJECTIVE : There are few estimates of the incidence and prevalence of inflammatory bowel disease in North American communities . We sought to estimate the incidence and prevalence of inflammatory bowel disease ( IBD ) , including Crohn 's disease ( CD ) , and ulcerative colitis ( UC ) , among 3.2 million members of Kaiser Permanente , Northern California , for the period 1996–2002 . METHODS : All health plan members who had one or more diagnoses of CD ( ICD-9 code 555 ) or UC ( ICD-9 code 556 ) on computerized records during the period 1996–2002 and with at least 12 months of membership were identified as possible IBD cases ( N = 12,059 ) . We r and omly sample d 24 % of these for chart review to confirm the diagnosis and obtain the initial diagnosis date . Incidence rates and the point prevalence on December 31 , 2002 were st and ardized to the 2000 U. S. Census . RESULTS : The annual incidence rate per 100,000 persons was 6.3 for CD ( 95 % confidence interval [ CI ] , 5.6–7.0 ) and 12.0 for UC ( CI , 11.0–13.0 ) . The point prevalence per 100,000 on December 31 , 2002 was 96.3 for CD ( 95 % CI , 89.6–103.0 ) and 155.8 for UC ( 95 % CI , 146.6–164.9 ) , increasing to 100.3 and 205.8 per 100,000 , respectively , when hospital discharge data from 1985 to 1995 were included . The age-specific incidence of CD was bimodal , while UC incidence rose in early adulthood and remained elevated with advancing age . CONCLUSIONS : The incidence we estimated for CD was similar to the previous U. S. estimate . Our incidence estimate for UC was much higher than the previous U.S. estimate , but similar to that of recent Canadian and European studies . The prevalence we estimated for CD was somewhat lower than previous estimates The epidemiology of inflammatory bowel disease is described among the more than 1.5 million members of the Kaiser Permanente Medical Care Program ( KPMCP ) in northern California . We review ed a 20 % r and om sample of the medical records of 2,067 persons first admitted to hospital in the period 1971 through 1982 with codes indicating inflammatory bowel disease . We also examined all new outpatient cases for a 1-year period from records at the Oakl and KPMCP facility . Criteria used to establish valid cases adhered to st and ards used in previous studies but were revised to reflect current diagnostic methods . The disadvantages of using hospital discharge data have been identified and quantified . In this population , only 21 % of ambulatory patients with inflammatory bowel disease were admitted to hospital in a 3 1/2-year period . There was no difference in the incidence of the disorder by sex or between whites and blacks , but it was rare in Asians . A bimodal age distribution was suggested for Crohn 's disease but not for ulcerative colitis . During the 12 years of this study , rates of hospital admissions for ulcerative colitis decreased and for Crohn 's disease were slightly increased Output:	The incidence and prevalence of IBD is increasing among minorities . There is less of a genetic influence in the pathogenesis of IBD among African Americans ; however , novel variants have been identified . There is a predilection for pancolonic ulcerative colitis among Hispanics and Asians . Crohn 's disease-related hospitalizations are increasing in Asians , whereas African Americans are more likely to use the emergency department . No major differences are seen in disease location and behavior , upper gastrointestinal tract , and perianal involvement and extraintestinal manifestations among races and ethnic groups . Medication utilization seems to be similar . Differences in surgery are likely explained by health insurance status .
MS22576	*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 H and exercises are recommended for patients with h and osteoarthritis ( HOA ) , though evidence for their effect is conflicting . Objective To evaluate , in a r and omised controlled trial , the effect of HOA information plus home-based h and exercises ( exercise group ) compared with information only ( control group ) in women with HOA . Methods Interventions were delivered by two occupational therapists . Exercise group participants received eight follow-up calls over the 3-month study and recorded adherence , pain after exercises and adverse events in a diary . Primary outcome was activity performance measured after 3 months by the Patient-Specific Functional Scale ( PSFS ) , with a range of 0–10 . Secondary outcomes were measurements of h and function , disease activity , symptoms and number of responders to treatment according to the OMERACT-OARSI criteria . Results Of 80 women r and omised ( 40 : 40 ) ( mean age ( SD ) 60.8 years ( 7.0 ) ) , follow-up was 89 % ( n=71 ) . An intention-to-treat analysis was performed . The adjusted mean difference for the exercise versus control group was 1.4 points ( 95 % CI 0.6 to 2.2 , effect size 1.0 ) for the PSFS score . Thirteen patients in the exercise group versus three participants in the control group reached a positive minimal clinical important difference of 2.2 points in the PSFS total score , while none versus two , respectively , had a negative change ( p=0.007 ) . For secondary outcomes , significant mean differences were found in grip strength and thumb web space , in fatigue , joint pain and the Functional Index for HOA activity performance scores . Sixteen exercise-group participants fulfilled the OMERACT-OARSI response criteria versus two control-group participants ( p<0.001 ) . Conclusions H and exercises were well tolerated and significantly improved activity performance , grip strength , pain and fatigue in women with HOA . Trial registration number : ISRTCN79019063 Background Osteoarthritis is the leading cause of disability in older adults . Evidence of effectiveness for self-management of h and osteoarthritis is lacking . Methods In this r and omised , factorial trial , we evaluated the effectiveness of joint protection versus no joint protection , and h and exercise versus no h and exercise in adults , 50 years of age or older , with h and osteoarthritis . Following a population survey ( n=12 297 ) , eligible individuals were r and omly assigned ( 1:1:1:1 ) to : leaflet and advice ; joint protection ; h and exercise ; joint protection plus h and exercise . Joint protection and h and exercises were delivered by nine occupational therapists , over four group sessions . The primary outcome was the OARSI/OMERACT responder criteria at 6 months . Outcomes were collected blind to allocation ( 3 , 6 , 12 m ) . Analysis was by intention to treat . Results Of 257 participants r and omised ( 65:62:65:65 ) ( mean age ( SD ) 66 years ( 9.1 ) ; female 66 % ) follow-up was 85 % at 6 m ( n=212 ) . Baseline characteristics and loss to follow-up were similar between groups . There were no reported treatment side effects . At 6 m 33 % assigned joint protection were responders compared with 21 % with no joint protection ( p=0.03 ) . Of those assigned h and exercises , 28 % were responders compared with 25 % with no exercises ( n.s . ) . Differences in secondary outcomes were not statistically significant , except for improvement in pain self-efficacy with joint protection ( 3 m p=0.002 ; 6 m p=0.001 ; 12 m p=0.03 ) . Conclusions These findings show that occupational therapists can support self-management in older adults with h and osteoarthritis , and that joint protection provides an effective intervention for medium term outcome . ( Funded by the Arthritis Research UK IS RCT N 33870549 ) OBJECTIVE To determine the effectiveness of a manual therapy program compared with an exercise therapy program in patients with osteoarthritis ( OA ) of the hip . METHODS A single-blind , r and omized clinical trial of 109 hip OA patients was carried out in the outpatient clinic for physical therapy of a large hospital . The manual therapy program focused on specific manipulations and mobilization of the hip joint . The exercise therapy program focused on active exercises to improve muscle function and joint motion . The treatment period was 5 weeks ( 9 sessions ) . The primary outcome was general perceived improvement after treatment . Secondary outcomes included pain , hip function , walking speed , range of motion , and quality of life . RESULTS Of 109 patients included in the study , 56 were allocated to manual therapy and 53 to exercise therapy . No major differences were found on baseline characteristics between groups . Success rates ( primary outcome ) after 5 weeks were 81 % in the manual therapy group and 50 % in the exercise group ( odds ratio 1.92 , 95 % confidence interval 1.30 , 2.60 ) . Furthermore , patients in the manual therapy group had significantly better outcomes on pain , stiffness , hip function , and range of motion . Effects of manual therapy on the improvement of pain , hip function , and range of motion endured after 29 weeks . CONCLUSION The effect of the manual therapy program on hip function is superior to the exercise therapy program in patients with OA of the hip Purpose The objective of this study was to evaluate whether women with knee osteoarthritis performing a rehabilitation programme consisting of low-load exercises combined with PVO exhibited the same results in changes in quadriceps strength , pain relief , and functional improvement when compared to women receiving a programme consisting of high-load exercises without PVO . Methods Thirty-four women ( mean age , 61 years ) with a diagnosis of knee osteoarthritis were r and omly assigned to a conventional or occlusion group . The women in the conventional group ( n = 17 ) performed a 6-week quadriceps strengthening and stretching programme using a load around 70 % of the 1-repetition maximum ( RM ) . The women in the occlusion group ( n = 17 ) performed the same programme , however , only using a load around 30 % of the 1-RM , while PVO was induced . The PVO was achieved using a pressure cuff applied to the upper third of the thigh and inflated to 200 mmHg during the quadriceps exercise . An 11-point Numerical Pain Rating Scale ( NPRS ) , the Lequesne question naire , the Timed-Up and Go ( TUG ) test , and muscle strength measurement using a h and -held dynamometer were used as outcome measures at baseline ( pretreatment ) and at the end of the 6-week of treatment . Pain , using the NPRS , was also assessed when performing the quadriceps exercises during the exercise sessions . Results At baseline , demographic , strength , pain , and functional assessment data were similar between groups . Patients from both the conventional and occlusion groups had a higher level of function ( Lequesne and TUG test ) , less pain ( NPRS ) , and higher quadriceps strength at the 6-week evaluation when compared to baseline ( all P < 0.05 ) . However , the between-group analysis showed no differences for all outcomes variables at posttreatment ( n.s . ) . Patients in the occlusion group experienced less anterior knee discomfort during the treatment sessions than those in the high-load exercise group ( P < 0.05 ) . Conclusion A rehabilitation programme that combined PVO to low-load exercise result ed in similar benefits in pain , function , and quadriceps strength than a programme using high-load conventional exercise in patients with knee osteoarthritis . However , the use of PVO combined with low-load exercise result ed in less anterior knee pain during the training sessions . Level of evidence 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 & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies OBJECTIVE To determine the clinical effectiveness of an exercise programme on self-reported h and activity performance in people with h and osteoarthritis ( OA ) . DESIGN In this r and omized , controlled trial , participants with physician-confirmed h and OA were r and omly allocated to a 12-week exercise intervention ( group- and home-based ) or usual care . The primary outcome was self-reported h and activity performance at 3 months measured by the Functional Index for H and Osteoarthritis ( FIHOA ) and a patient-generated measure of disability , the Patient-Specific Functional Scale ( PSFS ) . RESULTS Of 130 r and omized participants ( mean age 66 ( st and ard deviation ( SD ) 9 ) ; female 90 % ) , 120 ( 92 % ) and 119 ( 92 % ) completed the 3- and 6-month follow-ups . The adjusted mean difference for the exercise vs control group was -0.5 points ( 95 % confidence interval ( CI ) -1.6 , 0.6 ) for the FIHOA score ( 0 - 30 scale , 0 = best ) and 0.9 points ( 95 % CI 0.1 , 1.7 ) for the PSFS score ( 0 - 10 scale , 10 = best ) . Small significant mean differences in favour of the intervention group were found for h and pain , h and stiffness and disease activity , whereas no mean differences were observed in h and dexterity or maximal grip strength . A significantly larger proportion in the intervention ( 46 % ) vs control group ( 16 % ) fulfilled the Outcome Measures in Rheumatological Clinical Trials-Osteoarthritis Research Society International ( OMERACT-OARSI ) responder criteria at 3 months ( OR = 4.4 , 95 % CI 1.9 , 10.2 ) . At the 6-month follow-up , there were no significant group differences in any outcome . CONCLUSIONS The exercise programme was well tolerated among people with h and OA , but result ed only in small , beneficial short-term improvements on self-reported measures and not on most performance-based tests . Future studies should address optimal grip strength exercises and dosage . TRIAL REGISTRATION Clinical Trials.gov registration number : NCT01245842 STUDY DESIGN R and omized Clinical Trial . INTRODUCTION H and exercises have been recommended as treatment for h and osteoarthritis ( OA ) but research evidence is sparse . PURPOSE OF THE STUDY To investigate effects of daily 16-week home-based h and exercise among persons with h and OA . METHODS Forty-six older adults completed a crossover trial with washout between exercise and sham treatments . The AUSCAN physical function sub-scale served as the primary outcome measure . Other outcomes included pain and stiffness sub-scales , dexterity , and grip & pinch strengths . RESULTS Changes in AUSCAN sub-scales did not differ between exercise and sham treatments . No changes in dexterity were seen . Grip and pinch measures modestly improved after exercise but not sham . CONCLUSIONS It is possible that our exercise protocol may have been too ambitious for this age group . Future research will further the underst and ing of the role of h and exercise in h and OA symptomatology . LEVEL OF EVIDENCE 2b Abstract Background : Exercising is recommended for people with h and osteoarthritis ( HOA ) , but there is no consensus regarding the design of exercise programmes . Objective : To describe the development and content of an evidence -based exercise programme for people with HOA . Methods : The development was based on research evidence , professional expertise , and client evidence and adhered to the new Medical Research Council framework for design and evaluation of complex interventions . The process included literature search and appraisal , discussion s with clinicians and Output:	Conclusion There is no evidence that resistance training has a significant effect on grip strength or h and function in people with h and osteoarthritis . Low- quality evidence suggests it has a small , clinical ly unimportant pain-relieving effect .
MS22577	*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 This was a double-blind , multicenter study in which 410 adults ( ≥18 years of age ) with uncomplicated skin and soft tissue infections ( SSTIs ) were r and omized to receive either 400 mg of gatifloxacin orally once daily or 500 mg of levofloxacin orally once daily for 7 to 10 days . The study protocol called for four assessment s — before and during treatment , at the end of treatment , and posttreatment . Efficacy evaluations included clinical response and bacterial eradication rates . Of 407 treated patients , 202 ( 108 women , 94 men ) received gatifloxacin and 205 ( 111 women , 94 men ) received levofloxacin . For clinical ly evaluable patients , the cure rates were 91 % for gatifloxacin and 84 % for levofloxacin ( 95 % confidence interval [ CI ] for the difference , −2.0 to 15.2 % ) . Clinical cure rates for microbiologically evaluable patients were 93 % for gatifloxacin and 88 % for levofloxacin ( 95 % CI for the difference , −6.5 to 16.8 % ) . The bacterial eradication rate was 92 % for each group , with gatifloxacin eradicating 93 % of the methicillin-susceptible Staphylococcus aureus isolates and levofloxacin eradicating 91 % of them . Both drugs were well tolerated . Most of the adverse events were mild to moderate , and nausea was the most common adverse event in each treatment arm . Once-daily oral gatifloxacin ( 400 mg ) is clinical ly efficacious and well tolerated compared with once-daily levofloxacin ( 500 mg ) for the treatment of patients with uncomplicated SSTIs 112 patients admitted to hospital with a diagnosis of erysipelas , were r and omized to 8 days treatment with prednisolone or placebo in addition to antibiotics . 108 patients received the study drugs and were evaluated for time to cure , which was the primary end-point . The median healing time was significantly shorter in the prednisolone group , 5 days , vs 6 days in the placebo group ( p < 0.01 ) . The 90th percentile healing time was 10.0 days in the prednisolone group vs 14.6 days in the control group . The prednisolone-treated patients had a median length of hospital stay ( secondary end-point ) of 5 days vs 6 for the placebo-treated ( p < 0.01 ) . The median treatment time with intravenous antibiotics ( secondary end-point ) was 4 days in the placebo group , which was 1 day longer than in the prednisolone group ( p < 0.05 ) . 13 patients , 7 of whom received placebo , relapsed during the observation period of 3 weeks . The frequency of side effects attributable to the study drug was not higher in the prednisolone group In this prospect i ve study of cellulitis , several nonpharmacological factors were associated with lack of early response . Such early nonresponse was rarely related to inappropriate therapy but strongly predictive of early treatment escalation , suggesting that broadening antibiotic treatment often may be premature This prospect i ve study of cellulitis identified β-hemolytic streptococci as the dominating cause in all investigated subgroups . Group C/G streptococci were more frequently detected than group A streptococci . No single clinical feature substantially increased the probability of confirmed streptococcal etiology OBJECTIVES To determine whether outcomes for patients with cellulitis treated with oral antimicrobials are as good as for those who are treated with parenteral antimicrobials . METHODS A prospect i ve r and omized non-inferiority trial was conducted at a tertiary teaching hospital in Melbourne , Australia . Participants were patients referred by the emergency department for treatment of uncomplicated cellulitis with parenteral antimicrobials . Patients were r and omized to receive either oral cefalexin or parenteral cefazolin . Parenteral antimicrobials were changed to oral after the area of cellulitis ceased progressing . The primary outcome was days until no advancement of the area of cellulitis . A non-inferiority margin of 15 % was set for the oral arm compared with the parenteral arm . Secondary outcomes were failure of treatment , pain , complications and satisfaction with care . This trial is registered with the Australian New Zeal and Clinical Trials Registry ( ACTRN12611000685910 ) . RESULTS Twenty-four patients were r and omized to oral antimicrobials and 23 to parenteral antimicrobials . Mean days to no advancement of cellulitis was 1.29 ( SD 0.62 ) for the oral arm and 1.78 ( SD 1.13 ) for the parenteral arm , with a mean difference of -0.49 ( 95 % CI : -1.02 to + 0.04 ) . The upper limit of the 95 % CI of the difference in means of + 0.04 was below the 15 % non-inferiority margin of + 0.27 days , indicating non-inferiority . More patients failed treatment in the parenteral arm ( 5 of 23 , 22 % ) compared with the oral arm ( 1 of 24 , 4 % ) , although this difference was not statistically significant ( P=0.10 ) . Pain , complications and satisfaction with care were similar for both groups . CONCLUSIONS Oral antimicrobials are as effective as parenteral antimicrobials for the treatment of uncomplicated cellulitis BACKGROUND Cellulitis is a condition routinely encountered in the primary care setting . No previous study has compared a short ( 5 days ) vs st and ard ( 10 days ) course of therapy of the same antibiotic in patients with uncomplicated cellulitis . METHODS We performed a r and omized , double-blind , placebo-controlled trial to determine if 5 days of therapy has equal efficacy to 10 days of therapy for patients with cellulitis . Of 121 enrolled subjects evaluated after 5 days of therapy for cellulitis , 43 were r and omized to receive 5 more days of levofloxacin therapy ( 10 days total antibiotic treatment ) , and 44 subjects to receive 5 more days of placebo therapy ( 5 days of total antibiotic treatment ) . Levofloxacin was given at a dose of 500 mg/d . Subjects were not r and omized if they had worsening cellulitis , a persistent nidus of infection , a lack of any clinical improvement , or abscess formation within the first 5 days of therapy . The main outcome measure was resolution of cellulitis at 14 days , with absence of relapse by 28 days , after study enrollment . RESULTS Eighty-seven subjects were r and omized and analyzed by intention to treat . There was no significant difference in clinical outcome between the 2 courses of therapy ( success in 42 [ 98 % ] of 43 subjects receiving 10 days of antibiotic , and 43 [ 98 % ] of 44 subjects receiving 5 days of antibiotic ) at both 14 and 28 days of therapy . CONCLUSION In patients with uncomplicated cellulitis , 5 days of therapy with levofloxacin appears to be as effective as 10 days of therapy BACKGROUND New antibiotics are needed to treat infections caused by drug-resistant bacteria . Tedizolid is a novel oxazolidinone antibacterial drug design ed to provide enhanced activity against Gram-positive pathogens . We aim ed to assess the efficacy and safety of intravenous to oral tedizolid for treatment of patients with acute bacterial skin and skin-structure infections . METHODS ESTABLISH-2 was a r and omised , double-blind , phase 3 , non-inferiority trial done between Sept 28 , 2011 , and Jan 10 , 2013 , at 58 centres in nine countries . Patients ( aged ≥12 years ) with acute bacterial skin and skin-structure infections ( cellulitis or erysipelas , major cutaneous abscess , or wound infection ) that had a minimum lesion area of 75 cm(2 ) and were suspected or documented to be associated with a Gram-positive pathogen , were r and omly assigned ( 1:1 ) , via an interactive voice-response system with block r and omisation , to receive intravenous once-daily tedizolid ( 200 mg for 6 days ) or twice-daily linezolid ( 600 mg for 10 days ) , with optional oral step-down . R and omisation was stratified by geographic region and type of acute bacterial skin and skin-structure infection . The primary endpoint was early clinical response ( ≥20 % reduction in lesion area at 48 - 72 h compared with baseline ) , with a non-inferiority margin of -10 % . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT01421511 . FINDINGS 666 patients were r and omly assigned to receive tedizolid ( n=332 ) or linezolid ( n=334 ) . 283 ( 85 % ) patients in the tedizolid group and 276 ( 83 % ) in the linezolid group achieved early clinical response ( difference 2·6 % , 95 % CI -3·0 to 8·2 ) , meeting the prespecified non-inferiority margin . Gastrointestinal adverse events were less frequent with tedizolid than linezolid , taking place in 52 ( 16 % ) of 331 patients and 67 ( 20 % ) of 327 patients in the safety population . Treatment-emergent adverse events leading to discontinuation of study drug were reported by one ( < 1 % ) patient in the tedizolid group and four ( 1 % ) patients in the linezolid group . INTERPRETATION Intravenous to oral once-daily tedizolid 200 mg for 6 days was non-inferior to twice-daily linezolid 600 mg for 10 days for treatment of patients with acute bacterial skin and skin-structure infections . Tedizolid could become a useful option for the treatment of acute bacterial skin and skin-structure infections in the hospital and outpatient setting s. FUNDING Cubist Pharmaceuticals ABSTRACT Skin and soft tissue infections ( SSTIs ) are a common cause of morbidity in both the community and the hospital . An SSTI is classified as complicated if the infection has spread to the deeper soft tissues , if surgical intervention is necessary , or if the patient has a comorbid condition hindering treatment response ( e.g. , diabetes mellitus or human immunodeficiency virus ) . The purpose of this study was to compare linezolid to vancomycin in the treatment of suspected or proven methicillin-resistant gram-positive complicated SSTIs ( CSSTIs ) requiring hospitalization . This was a r and omized , open-label , comparator-controlled , multicenter , multinational study that included patients with suspected or proven methicillin-resistant Staphylococcus aureus ( MRSA ) infections that involved substantial areas of skin or deeper soft tissues , such as cellulitis , abscesses , infected ulcers , or burns ( < 10 % of total body surface area ) . Patients were r and omized ( 1:1 ) to receive linezolid ( 600 mg ) every 12 h either intravenously ( i.v . ) or orally or vancomycin ( 1 g ) every 12 h i.v . In the intent-to-treat population , 92.2 % and 88.5 % of patients treated with linezolid and vancomycin , respectively , were clinical ly cured at the test-of-cure ( TOC ) visit ( P = 0.057 ) . Linezolid outcomes ( 124/140 patients or 88.6 % ) were superior to vancomycin outcomes ( 97/145 patients or 66.9 % ) at the TOC visit for patients with MRSA infections ( P < 0.001 ) . Drug-related adverse events were reported in similar numbers in both the linezolid and the vancomycin arms of the trial . The results of this study demonstrate that linezolid therapy is well tolerated , equivalent to vancomycin in treating CSSTIs , and superior to vancomycin in the treatment of CSSTIs due to MRSA In this double-blind , r and omised trial conducted in 22 centres in the USA , azithromycin given over five days , as a once-a-day regimen , ( 500 mg on day 1 , 250 mg on days 2–5 ) was compared with cephalexin ( 500 mg b.i.d . ) given for ten days in the treatment of patients with skin and skin structure infections . A total of 366 patients entered the study and 179 of these were eligible for the efficacy analysis . The overall clinical response to azithromycin was 94.0 % , compared with 95.8 % for cephalexin . The clinical cure rates were 53.0 % for azithromycin and 59.4 % for cephalexin ; the respective improvement rates were 41.0 % and 36.5 % . Distribution of response ( cured , improved , failed ) was similar in each group ( p=0.37 ) . The bacter Output:	For trials assessing prevention of cellulitis , recurrence was the key outcome measure . From the cellulitis PSP , prevention of recurrence , clinical features and long-term disease impact were the most important outcome themes for patients . We have shown that in cellulitis treatment and prevention research , there is significant heterogeneity in clinical outcomes , inadequate focus on patient-reported outcomes , and a disparity between what is currently measured and what patients and healthcare professionals feel is important .
MS22578	*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 Neonatal deaths in developing countries make the largest contribution to global mortality in children younger than 5 years . 90 % of deliveries in the poorest quintile of households happen at home . We postulated that a community-based participatory intervention could significantly reduce neonatal mortality rates . METHODS We pair-matched 42 geopolitical clusters in Makwanpur district , Nepal , selected 12 pairs r and omly , and r and omly assigned one of each pair to intervention or control . In each intervention cluster ( average population 7000 ) , a female facilitator convened nine women 's group meetings every month . The facilitator supported groups through an action-learning cycle in which they identified local perinatal problems and formulated strategies to address them . We monitored birth outcomes in a cohort of 28?931 women , of whom 8 % joined the groups . The primary outcome was neonatal mortality rate . Other outcomes included stillbirths and maternal deaths , uptake of antenatal and delivery services , home care practice s , infant morbidity , and health-care seeking . Analysis was by intention to treat . The study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N31137309 . FINDINGS From 2001 to 2003 , the neonatal mortality rate was 26.2 per 1000 ( 76 deaths per 2899 livebirths ) in intervention clusters compared with 36.9 per 1000 ( 119 deaths per 3226 livebirths ) in controls ( adjusted odds ratio 0.70 [ 95 % CI 0.53 - 0.94 ] ) . Stillbirth rates were similar in both groups . The maternal mortality ratio was 69 per 100000 ( two deaths per 2899 livebirths ) in intervention clusters compared with 341 per 100000 ( 11 deaths per 3226 livebirths ) in control clusters ( 0.22 [ 0.05 - 0.90 ] ) . Women in intervention clusters were more likely to have antenatal care , institutional delivery , trained birth attendance , and hygienic care than were controls . INTERPRETATION Birth outcomes in a poor rural population improved greatly through a low cost , potentially sustainable and scalable , participatory intervention with women 's groups The “ Health for All Project ” ( HFAP ) policy in Nigeria was complemented by the National Drug Policy to ensure constant availability of high quality drugs and medical consumables at affordable prices to citizens in public hospitals . Apart from strengthening the utilization of health services , the project also sought to improve health care delivery for the poor who could not afford the high cost of drugs in private clinics and pharmaceutical stores . Employing a survey method with stratified and systematic r and om techniques , the study found failed expectations in the promises of HFAP policy among the 1250 low-income women in Uyo urban . In the face of “ stock out ” where most drugs , pharmaceuticals , and medical supplies are consistently not available for dispensing in public hospitals and health centers poor urban women resorted to alternative health care in prayer houses , herbal homes , patent medicine vendors , health workers homes , and traditional birth attendants . The study reported that stock out in government health facilities result ed in health hazards and the relapse of illnesses as a result of non-adherence to treatment regime and exposure to fake , expired , and adulterated drugs . A renewed commitment in health care delivery in Nigeria is called for if poor women are to be really empowered BACKGROUND Community mobilisation through participatory women 's groups might improve birth outcomes in poor rural communities . We therefore assessed this approach in a largely tribal and rural population in three districts in eastern India . METHODS From 36 clusters in Jharkh and and Orissa , with an estimated population of 228 186 , we assigned 18 clusters to intervention or control using stratified r and omisation . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study . In intervention clusters , a facilitator convened 13 groups every month to support participatory action and learning for women , and facilitated the development and implementation of strategies to address maternal and newborn health problems . The primary outcomes were reductions in neonatal mortality rate ( NMR ) and maternal depression scores . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N21817853 . FINDINGS After baseline surveillance of 4692 births , we monitored outcomes for 19 030 births during 3 years ( 2005 - 08 ) . NMRs per 1000 were 55.6 , 37.1 , and 36.3 during the first , second , and third years , respectively , in intervention clusters , and 53.4 , 59.6 , and 64.3 , respectively , in control clusters . NMR was 32 % lower in intervention clusters adjusted for clustering , stratification , and baseline differences ( odds ratio 0.68 , 95 % CI 0.59 - 0.78 ) during the 3 years , and 45 % lower in years 2 and 3 ( 0.55 , 0.46 - 0.66 ) . Although we did not note a significant effect on maternal depression overall , reduction in moderate depression was 57 % in year 3 ( 0.43 , 0.23 - 0.80 ) . INTERPRETATION This intervention could be used with or as a potential alternative to health-worker-led interventions , and presents new opportunities for policy makers to improve maternal and newborn health outcomes in poor population s. FUNDING Health Foundation , UK Department for International Development , Wellcome Trust , and the Big Lottery Fund ( UK ) Background Globally , puerperal sepsis accounts for an estimated 8–12 % of maternal deaths , but evidence is lacking on the extent to which clean delivery practice s could improve maternal survival . We used data from the control arms of four cluster-r and omised controlled trials conducted in rural India , Bangladesh and Nepal , to examine associations between clean delivery kit use and h and washing by the birth attendant with maternal mortality among home deliveries . Methods We tested associations between clean delivery practice s and maternal deaths , using a pooled data set for 40,602 home births across sites in the three countries . Cross-sectional data were analysed by fitting logistic regression models with and without multiple imputation , and confounders were selected a priori using causal directed acyclic graphs . The robustness of estimates was investigated through sensitivity analyses . Results H and washing was associated with a 49 % reduction in the odds of maternal mortality after adjusting for confounding factors ( adjusted odds ratio ( AOR ) 0.51 , 95 % CI 0.28–0.93 ) . The sensitivity analysis testing the missing at r and om assumption for the multiple imputation , as well as the sensitivity analysis accounting for possible misclassification bias in the use of clean delivery practice s , indicated that the association between h and washing and maternal death had been over estimated . Clean delivery kit use was not associated with a maternal death ( AOR 1.26 , 95 % CI 0.62–2.56 ) . Conclusions Our evidence suggests that h and washing in delivery is critical for maternal survival among home deliveries in rural South Asia , although the exact magnitude of this effect is uncertain due to inherent biases associated with observational data from low re source setting s. Our findings indicating kit use does not improve maternal survival , suggests that the soap is not being used in all instances that kit use is being reported Introduction Mother-to-child transmission of HIV can be reduced to<5 % with appropriate antiretroviral medications . Such reductions depend on multiple health system encounters during antenatal care ( ANC ) , delivery and breastfeeding ; in countries with limited access to care , transmission remains high . In Lesotho , where 28 % of women attending ANC are HIV positive but where geographic and other factors limit access to ANC and facility deliveries , a Minimum PMTCT Package was launched in 2007 as an alternative to the existing facility-based approach . Distributed at the first ANC visit , it packaged together all necessary pregnancy , delivery and early postnatal antiretroviral medications for mother and infant . Methods To examine the availability , feasibility , acceptability and possible negative consequences of the Minimum PMTCT Package , data from a 2009 qualitative and quantitative study and a 2010 facility assessment were used . To examine the effects on ANC and facility-based delivery rates , a difference-in-differences analytic approach was applied to 2009 Demographic and Health Survey data for HIV-tested women who gave birth before and after Minimum PMTCT Package implementation . Results The Minimum PMTCT Package was feasible and acceptable to providers and clients . Problems with test kit and medicine stock-outs occurred , and 46 % of women did not receive the Minimum PMTCT Package until at least their second ANC visit . Providing adequate instruction on the use of multiple medications represented a challenge . The proportion of HIV-positive women delivering in facilities declined after Minimum PMTCT Package implementation , although it increased among HIV-negative women ( difference-in-differences=14.5 % , p=0.05 ) . The mean number of ANC visits declined more among HIV-positive women than among HIV-negative women after implementation , though the difference was not statistically significant ( p=0.09 ) . Changes in the percentage of women receiving≥4 ANC visits did not differ between the two groups . Conclusions If supply issues can be resolved and adequate client educational material s provided , take-away co-packages have the potential to increase access to PMTCT commodities in countries where women have limited access to health services . However , efforts must be made to carefully monitor potential changes in ANC visits and facility deliveries , and further evaluation of adherence , safety and effectiveness are needed BACKGROUND There are approximately 4 million neonatal deaths and half a million maternal deaths worldwide each year . There is limited evidence from clinical trials to guide the development of effective maternity services in developing countries . METHODS We performed a cluster-r and omized , controlled trial involving seven subdistricts ( talukas ) of a rural district in Pakistan . In three talukas r and omly assigned to the intervention group , traditional birth attendants were trained and issued disposable delivery kits ; Lady Health Workers linked traditional birth attendants with established services and documented processes and outcomes ; and obstetrical teams provided outreach clinics for antenatal care . Women in the four control talukas received usual care . The primary outcome measures were perinatal and maternal mortality . RESULTS Of the estimated number of eligible women in the seven talukas , 10,114 ( 84.3 percent ) were recruited in the three intervention talukas , and 9443 ( 78.7 percent ) in the four control talukas . In the intervention group , 9184 women ( 90.8 percent ) received antenatal care by trained traditional birth attendants , 1634 women ( 16.2 percent ) were seen antenatally at least once by the obstetrical teams , and 8172 safe-delivery kits were used . As compared with the control talukas , the intervention talukas had a cluster-adjusted odds ratio for perinatal death of 0.70 ( 95 percent confidence interval , 0.59 to 0.82 ) and for maternal mortality of 0.74 ( 95 percent confidence interval , 0.45 to 1.23 ) . CONCLUSIONS Training traditional birth attendants and integrating them into an improved health care system were achievable and effective in reducing perinatal mortality . This model could result in large improvements in perinatal and maternal health in developing countries OBJECTIVE To determine the feasibility and acceptability of providing clean birth kits ( CBKs ) containing misoprostol for self-administration in a rural setting in Papua New Guinea . METHODS A prospect i ve intervention study was conducted between April 8 , 2013 , and October 24 , 2014 . Eligible participants were women in the third trimester of pregnancy who attended a prenatal clinic in Unggai Bena . Participants received individual instruction and were then given a CBK containing 600μg misoprostol tablets for self-administration following an unsupervised birth if they could demonstrate their underst and ing of correct use of items in the CBK . Data regarding the use and acceptability of the CBK and misoprostol were collected during postpartum follow-up . RESULTS Among 200 participants , 106 ( 53.0 % ) had an unsupervised birth , and 99 ( 93.4 % ) of these women used the CBK . All would use the CBK again and would recommend it to others . Among these 99 women , misoprostol was self-administered by 98 ( 99.0 % ) , all of whom would take the drug again and would recommend it to others . CONCLUSION The findings strengthen the case for community-based use of misoprostol to prevent postpartum hemorrhage in remote communities . Large-scale interventions should be planned to further evaluate impact and acceptability Output:	Conclusion This review suggests potential benefits in the use of supply kits to improve maternal and neonatal health .
MS22579	*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 Data regarding the efficacy of directly administered antiretroviral therapy ( DAART ) are mixed . Opioid treatment programs ( OTPs ) provide a convenient framework for DAART . In a r and omized controlled trial , we compared DAART and self-administered therapy ( SAT ) among HIV-infected subjects attending five OTPs in Baltimore , MD . Methods HIV-infected individuals attending OTPs were eligible if they were not taking antiretroviral therapy ( ART ) or were virologically failing ART at last clinical assessment . In subjects assigned to DAART , we observed one ART dose per weekday at the OTP for up to 12 months . SAT subjects administered ART at home . The primary efficacy comparison was the between-arm difference in the average proportions with HIV RNA < 50 copies/mL during the intervention phase ( 3- , 6- , and 12-month study visits ) , using a logistic regression model accounting for intra-person correlation due to repeated observations . Adherence was measured with electronic monitors in both arms . Results We r and omized 55 and 52 subjects from five Baltimore OTPs to DAART and SAT , respectively . The average proportions with HIV RNA < 50 copies/mL during the intervention phase were 0.51 in DAART and 0.40 in SAT ( difference 0.11 , 95 % CI : −0.020 to 0.24 ) . There were no significant differences between arms in electronically-measured adherence , average CD4 cell increase from baseline , average change in log10 HIV RNA from baseline , opportunistic conditions , hospitalizations , mortality , or the development of new drug resistance mutations . Conclusions In this r and omized trial , we found little evidence that DAART provided clinical benefits compared to SAT among HIV-infected subjects attending OTPs . Trial Registration Clinical Trails.gov NCT00279110 NCT00279110?term = NCT00279110&rank = Background There are conflicting reports of antiretroviral therapy ( ART ) effectiveness comparisons between primary healthcare ( PHC ) facilities and hospitals in low-income setting s. This comparison has not been evaluated on a broad scale in South Africa . Methodology /Principal Findings A retrospective cohort study was conducted including ART-naïve adults from 59 facilities in four provinces in South Africa , enrolled between 2004 and 2007 . Kaplan-Meier estimates , competing-risks Cox regression , generalised estimating equation population -averaged models and logistic regression were used to compare death , loss to follow-up ( LTFU ) and virological suppression ( VS ) between PHC , district and regional hospitals . 29 203 adults from 47 PHC facilities , nine district hospitals and three regional hospitals were included . Patients at PHC facilities had more advanced WHO stage disease when starting ART . Retention in care was 80.1 % ( 95 % CI : 79.3%–80.8 % ) , 71.5 % ( 95 % CI : 69.1%–73.8 % ) and 68.7 % ( 95 % CI : 67.0%–69.7 % ) at PHC , district and regional hospitals respectively , after 24 months of treatment ( P<0.0001 ) . In adjusted regression analyses , LTFU was independently increased at regional hospitals ( aHR 2.19 ; 95 % CI : 1.94−2.47 ) and mortality was independently elevated at district hospitals ( aHR 1.60 ; 95 % CI : 1.30−1.99 ) compared to PHC facilities after 12 months of ART . District and regional hospital patients had independently reduced probabilities of VS , aOR 0.76 ( 95 % CI : 0.59−0.97 ) and 0.64 ( 95 % CI : 0.56−0.75 ) respectively compared to PHC facilities over 24 months of treatment . Conclusions / Significance ART outcomes were superior at PHC facilities , despite PHC patients having more advanced clinical stage disease when starting ART , suggesting that ART can be adequately provided at this level and supporting the South African government 's call for rapid up-scaling of ART at the primary level of care . Further prospect i ve research is required to determine the degree to which outcome differences are attributable to either facility level characteristics or patient co-morbidity at hospital level Summary Background Robust evidence of the effectiveness of task shifting of antiretroviral therapy ( ART ) from doctors to other health workers is scarce . We aim ed to assess the effects on mortality , viral suppression , and other health outcomes and quality indicators of the Streamlining Tasks and Roles to Exp and Treatment and Care for HIV ( STRETCH ) programme , which provides educational outreach training of nurses to initiate and represcribe ART , and to de central ise care . Methods We undertook a pragmatic , parallel , cluster-r and omised trial in South Africa between Jan 28 , 2008 , and June 30 , 2010 . We r and omly assigned 31 primary -care ART clinics to implement the STRETCH programme ( intervention group ) or to continue with st and ard care ( control group ) . The ratio of r and omisation depended on how many clinics were in each of nine strata . Two cohorts were enrolled : eligible patients in cohort 1 were adults ( aged ≥16 years ) with CD4 counts of 350 cells per μL or less who were not receiving ART ; those in cohort 2 were adults who had already received ART for at least 6 months and were being treated at enrolment . The primary outcome in cohort 1 was time to death ( superiority analysis ) . The primary outcome in cohort 2 was the proportion with undetectable viral loads ( < 400 copies per mL ) 12 months after enrolment ( equivalence analysis , prespecified difference < 6 % ) . Patients and clinicians could not be masked to group assignment . The interim analysis was blind , but data analysts were not masked after the data base was locked for final analysis . Analyses were done by intention to treat . This trial is registered , number IS RCT N46836853 . Findings 5390 patients in cohort 1 and 3029 in cohort 2 were in the intervention group , and 3862 in cohort 1 and 3202 in cohort 2 were in the control group . Median follow-up was 16·3 months ( IQR 12·2–18·0 ) in cohort 1 and 18·0 months ( 18·0–18·0 ) in cohort 2 . In cohort 1 , 997 ( 20 % ) of 4943 patients analysed in the intervention group and 747 ( 19 % ) of 3862 in the control group with known vital status at the end of the trial had died . Time to death did not differ ( hazard ratio [ HR ] 0·94 , 95 % CI 0·76–1·15 ) . In a preplanned subgroup analysis of patients with baseline CD4 counts of 201–350 cells per μL , mortality was slightly lower in the intervention group than in the control group ( 0·73 , 0·54–1.00 ; p=0·052 ) , but it did not differ between groups in patients with baseline CD4 of 200 cells per μL or less ( 0·94 , 0·76–1·15 ; p=0·577 ) . In cohort 2 , viral load suppression 12 months after enrolment was equivalent in intervention ( 2156 [ 71 % ] of 3029 patients ) and control groups ( 2230 [ 70 % ] of 3202 ; risk difference 1·1 % , 95 % CI −2·4 to 4·6 ) . Interpretation Expansion of primary -care nurses ' roles to include ART initiation and represcription can be done safely , and improve health outcomes and quality of care , but might not reduce time to ART or mortality . Funding UK Medical Research Council , Development Cooperation Irel and , and Canadian International Development Agency BACKGROUND Untreated opioid dependence adversely affects the care of human immunodeficiency virus (HIV)-positive patients . Buprenorphine , a partial opioid agonist , is available for maintenance treatment of opioid dependence in HIV specialty setting s. We investigated the feasibility and efficacy of integrating buprenorphine , along with 2 levels of counseling , into HIV clinical care . METHODS HIV-positive , opioid-dependent patients were enrolled in a 12-week pilot study and r and omized to receive daily buprenorphine/naloxone treatment along with either brief physician management or physician management combined with nurse-administered drug counseling and adherence management . Primary outcomes included treatment retention ; illicit drug use , assessed by urine toxicology test and self-report ; CD4 lymphocyte counts ; and log(10 ) HIV type 1 ( HIV-1 ) RNA levels . RESULTS Of the 16 patients who received at least 1 dose of buprenorphine , 13 ( 81 % ) completed 12 weeks of treatment . The proportion of opioid-positive weekly urine test results decreased from 100 % at baseline to 32 % ( month 1 ) , 20 % ( month 2 ) , and 16 % ( month 3 ) . Only 4 patients reported any opioid use ( in the prior 7 days ) during the 12-week study . CD4 lymphocyte counts remained stable over the course of the study . The mean log(10 ) HIV-1 RNA level ( + /- st and ard deviation ) declined significantly , from 3.66+/-1.06 log(10 ) HIV-1 RNA copies/mL at baseline to 3.0+/-0.57 log(10 ) HIV-1 RNA copies/mL at month 3 ( P<.05 ) . No significant differences based on counseling intervention were detected . All 13 patients who completed the study continued to receive treatment in an extension phase of at least 0 - 15 months ' duration . CONCLUSIONS We conclude that it is feasible to integrate buprenorphine into HIV clinical care for the treatment of opioid dependence . Patients experienced good treatment retention and reductions in their opioid use . HIV biological markers remained stable or improved during buprenorphine/naloxone treatment BACKGROUND Exp and ed access to combination antiretroviral therapy ( ART ) in re source -poor setting s is dependent on task shifting from doctors to other health-care providers . We compared outcomes of nurse versus doctor management of ART care for HIV-infected patients . METHODS This r and omised non-inferiority trial was undertaken at two South African primary -care clinics . HIV-positive individuals with a CD4 cell count of less than 350 cells per microL or WHO stage 3 or 4 disease were r and omly assigned to nurse-monitored or doctor-monitored ART care . Patients were r and omly assigned by stratified permuted block r and omisation , and neither the patients nor those analysing the data were masked to assignment . The primary objective was a composite endpoint of treatment-limiting events , incorporating mortality , viral failure , treatment-limiting toxic effects , and adherence to visit schedule . Analysis was by intention to treat . Non-inferiority of the nurse versus doctor group for cumulative treatment failure was prespecified as an upper 95 % CI for the hazard ratio that was less than 1.40 . This study is registered with Clinical Trials.gov , number NCT00255840 . FINDINGS 408 patients were assigned to doctor-monitored ART care and 404 to nurse-monitored ART care ; all participants were analysed . 371 ( 46 % ) patients reached an endpoint of treatment failure : 192 ( 48 % ) in the nurse group and 179 ( 44 % ) in the doctor group . The hazard ratio for composite failure was 1.09 ( 95 % CI 0.89 - 1.33 ) , which was within the limits for non-inferiority . After a median follow-up of 120 weeks ( IQR 60 - 144 ) , deaths ( ten vs 11 ) , virological failures ( 44 vs 39 ) , toxicity failures ( 68 vs 66 ) , and programme losses ( 70 vs 63 ) were similar in nurse and doctor groups , respectively . INTERPRETATION Nurse-monitored ART is non-inferior to doctor-monitored therapy . Findings from this study lend support to task shifting to appropriately trained nurses for monitoring of ART . FUNDING National Institutes of Health ; United States Agency for International Development ; National Institute of Allergy and Infectious Diseases Objectives : To assess whether community-based care delivered by people living with HIV/AIDS ( PLWAs ) could replace clinic-based HIV care . Design : Prospect i ve cluster r and omized controlled clinical trial . Setting : Villages surrounding 1 rural clinic in western Kenya . Subjects : HIV-infected adults clinical ly stable on antiretroviral therapy ( ART ) . Intervention : The intervention group received monthly Personal Digital Assistant supported home assessment s by PLWAs with clinic appointments every 3 months . The control group received st and ard of care monthly clinic visits . Main Outcomes Measured : Viral load , CD4 count , Karnofsky score , stability of ART regimen , opportunistic infections , pregnancies , and number of clinic visits . Results : After 1 year , Output:	The limited data on ART integration into OST services indicated comparable rates of ART coverage , retention , and mortality . CONCLUSION Integrating ART into MNCH , TB , and OST services was often associated with improvements in ART coverage , and de central ization of ART into primary health facilities and communities was often associated with improved retention . Neither integration nor de central ization was associated with adverse outcomes .
MS22580	*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 purpose of this study was to investigate the effects of oral care using simple tools and methods on the cleanliness of the oral cavity in the elderly . Enrolled were 84 elderly subjects with a mean ( + /-S.D ) age of 85.1+/-7.0 years in a nursing home . They were given tongue and oral mucosa cleaning ( the oral care ) after lunch every day or every other day for two consecutive weeks by the authors . The effect of the oral care was studied in terms of C and ida scores in tongue coating , concentration of volatile sulfur compounds ( VSC ) which are the main causative substance of bad breath , and change in tongue coating scores . The above parameters were measured five times ; just before the oral care program , weekly during , and at the end of the oral care program . The groups of patients , who were given the oral care , especially the group of patients cared with sponge brushes every day , showed a significant reduction in C and ida scores but not in VSC concentration and tongue coating scores . The present method of oral care proved effective in cleaning the tongue and oral mucosa , and the C and ida scores appeared to be a reliable indicator for evaluation . It is suggested that this way of oral care is simple , easy and useful not only for the elderly at a nursing home but for the house-bound elder people who will rapidly increase in the near future in Japan PURPOSE The aim of this r and omised single-blind , cross-over trial was to assess the effect of tongue cleansing on morning oral malodour in periodontally healthy subjects . MATERIAL S AND METHODS Ten systemically healthy non-smoker subjects ( 6 males , 4 females ) , 24 - 38 years of age , completed two 4-day periods of oral hygiene cessation with a 7-day wash-out period . In one of these test periods , subjects were instructed to clean their tongues with a tongue scraper 2 - 3 times a day . Participants presented at least 20 teeth , without cavities , overhanging restorations/prostheses or periodontitis , and had no history of previous periodontal therapy or use of antibiotics in the 3 months prior to the study . Volatile sulphur compounds ( VSC ; Interscan Halimeter ) and organoleptic scores were measured in exhaled mouth air once a day , early in the morning , by one examiner . Comparisons were performed using Wilcoxon 's signed rank test and Friedman 's test ( alpha = 0.05 ) . RESULTS VSC levels at baseline were 206.3 ppb ( SD 139.8 ) and 191.4 ppb ( SD 127.7 ) for periods of usage and non-usage of the scraper respectively ( p > 0.05 ) . VSC levels did not change significantly during the 4 days , independent of tongue cleansing ( Friedman , p > 0.05 ) . Only at day 3 did the use of the tongue scraper lead to a significantly lower level of VSC compared with controls ( 131.1 ppb and 199.3 ppb respectively ) . No significant differences in organoleptic scores were observed between groups at baseline . During the whole experimental period , there were also no significant changes in organoleptic scores when individuals used or did not use the tongue scraper . CONCLUSION Tongue cleansing with a scraper was unable to prevent morning oral malodour in the absence of tooth cleaning in periodontally healthy individuals The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . For centuries , specific instruments or regular toothbrushes have routinely been used to remove tongue biofilm and improve breath odor . Toothbrushes with a tongue scraper on the back of their head have recently been introduced to the market . The present study compared the effectiveness of a manual toothbrush with this new design , i.e. , possessing a tongue scraper , and a commercial tongue scraper in improving breath odor and reducing the aerobic and anaerobic microbiota of tongue surface . The evaluations occurred at 4 moments , when the participants ( n=30 ) had their halitosis quantified with a halimeter and scored according to a 4-point scoring system corresponding to different levels of intensity . Saliva was collected for counts of aerobic and anaerobic microorganisms . Data were analyzed statistically by Friedman 's test ( p<0.05 ) . When differences were detected , the Wilcoxon test adjusted for Bonferroni correction was used for multiple comparisons ( group to group ) . The results confirmed the importance of mechanical cleaning of the tongue , since this procedure provided an improvement in halitosis and reduction of aerobe and anaerobe counts . Regarding the evaluated methods , the toothbrush 's tongue scraper and conventional tongue scraper had a similar performance in terms of breath improvement and reduction of tongue microbiota , and may be indicated as effective methods for tongue cleaning Bacterial proliferation and plaque accumulation on the surface of the tongue are major factors contributing to oral malodor . In this research , we used subjective and objective methods to evaluate the breath benefit of a triclosan-containing dentifrice ( Blend-a-Med Complete Night ) with and without tongue brushing in a r and omized , examiner-blinded , three-period crossover clinical trial . Twenty-nine adults ( mean age 40.2 years ) with morning malodor were r and omly assigned to a treatment sequence : triclosan dentifrice , triclosan dentifrice plus tongue brushing , and a control dentifrice ( Crest Cavity Protection ) . The subjects used each product four times in 27 h with a 2-day wash-out period between treatments . Halimeter measurements were taken at baseline and at 3 , 24 and 27 h. Subject question naire data assessing the breath quality were collected at 24 and 27 h. Both triclosan regimens showed significant improvement in oral malodor ( p<0.03 ) relative to the control . Significant ( p=0.035 ) malodor benefit was observed when tooth brushing with triclosan dentifrice was supplemented with tongue brushing . The triclosan dentifrice was associated with significant improvement ( p<0.05 ) in morning mouth feel and feeling of clean and fresh breath during the day relative to the control . There were no adverse events reported . The triclosan dentifrice was effective against overnight and daytime oral malodor . Supplementing routine brushing with tongue brushing result ed in additional breath improvement and breath benefits of the triclosan dentifrice were first-person noticeable PURPOSE S To compare the oral malodor protection efficacy of a 0.454 % stannous fluoride dentifrice versus a negative control ( 0.243 % sodium fluoride ) using a sulfide monitor ( halimeter ) as the measurement . A secondary objective was to assess the effects of tongue brushing . METHODS This was a four-treatment , five-period , examiner-blinded , crossover , r and omized study . Healthy subjects who met the entrance criteria were enrolled into the study . A 5-day acclimation period , in which subjects brushed twice daily in their customary manner with a st and ard sodium fluoride dentifrice , occurred prior to baseline . After baseline halimeter measurements , subjects were r and omly assigned to one of four treatments ( SnF2 dentifrice groups , with or without tongue brushing ; negative control dentifrice groups , with or without tongue brushing ) based on baseline halimeter scores , age , and gender . Test products were used three times a day . Breath measurements were taken 24 hours after baseline ( after three product uses ) . Subjects then brushed again with the product treatment . Final breath measurements were taken 4 hours later , 28 hours after baseline . A 5-day washout separated each treatment period . RESULTS 33 subjects were enrolled and completed the study . The adjusted mean volatile sulfur compound ( VSC ) levels were significantly lower in the SnF2 groups than the NaF groups , at both 24 ( P < 0.01 ) and 28 ( P < 0.001 ) hours post baseline time points . Tongue brushing did not provide additional statistically significant breath benefits when compared to toothbrushing alone . Both dentifrices were well tolerated BACKGROUND It is estimated that approximately 85 % of all halitosis cases have their origin within the mouth ; of these , 50 % are caused by tongue residues . Previous studies have established that hydrogen sulfide and mercaptans are the primary components of halitosis . Thus , tongue cleaning gains importance as a means of halitosis management . METHODS This investigation compared the efficacy of two mechanical methods for tongue cleaning through a h and held sulfide monitor . This crossover trial was carried out with 10 healthy subjects , 20 to 50 years old . Before the baseline measurement of the volatile sulfur compounds ( VSCs ) , the subjects were instructed to refrain from any tongue cleaning method for 48 hours . The 10 participants were then placed in one of two groups ( five each ) : 1 ) first week : tongue scraper , second week : soft-bristle toothbrush ; 2 ) first week : toothbrush , second week : tongue scraper , with a 48-hour wash-out period between each week . RESULTS The baseline measurements were compared with those of the end of each week using the Dunn method ( alpha = 0.01 ) . The tongue scraper showed a 75 % reduction in VSCs , while the toothbrush only achieved a 45 % reduction in VSCs . CONCLUSION Although the tongue coating was removed by both methods , the tongue scraper performed better in reducing the production of volatile sulfur compounds Tongue cleaning is an ancient habit . Recent literature has shown that tongue cleaning leads to healthy oral environment . The aims of this study were to assess the effect of tongue scraper among male adult patients with caries and periodontal disease , on Mutans streptococci ( MS ) and Lactobacilli ( Lb ) bacteria and secondly to assess the effect on self perceived oral malodour . Sixty male patients completed the study . The age ranged from 20 - 55 years ( 32 + /- 9.53 ) . Fifty percent of the subjects were with university education level . Mean DMFT score was 9.17 ( + /-5.46 ) , while 88 % of the subjects were with early to moderate periodontitis assessed by CPITN . Thirty one percent of the subjects were smoker , while 86.7 % had tea/coffee drinking habit and tooth brushing . Only 28 % cl aim ed of using miswak ( chewing stick ) . All patients were advised to use a tongue scraper twice daily for at least 2 minutes per day for 7 days . No effort was made to change tooth brushing or dietary habits of patients . Self perceived oral malodour was reported by 41.7 % at baseline and 30 % after use of tongue scraper . Salivary count of Mutans Streptococci and Lactobacilli had significant decrease 3.37 ( + /- 0.71 ) to 2.27 ( + /- 0.80 ) and 3.22 ( + /- 0.85 ) to 2.32 ( + /- 0.87 ) respectively ( P = 0.000 ) . It was concluded that tongue scraping twice daily for 7 days had significant effect on MS and Lb bacteria and also decreased oral OBJECTIVES To characterize a comprehensive outline of the oral microflora related to pneumonia in older adults . DESIGN Prospect i ve and retrospective longitudinal study . SETTING Community . PARTICIPANTS Long-term hospitalized patients and people in nursing homes ( 343 subjects , aged > or = 65 ) . MEASUREMENTS Subjects were assessed at baseline for pneumonia-related health problems . The flora of the tongue coating was characterized according to terminal restriction fragment length polymorphism ( T-RFLP ) analysis . All subjects were followed prospect ively for 6 months for a diagnosis of pneumonia . The number of febrile days ( > 37.5 degrees C ) was assessed in 299 subjects who were observed for 12 months ( retrospectively for 6 months and prospect ively for 6 months ) . The follow-up data were analyzed using multivariate regression analyses in relation to the baseline data , including T-RFLP patterns . RESULTS T-RFLP patterns outlining the floral composition of the tongue coating were grouped into Clusters A , B , C , and D. According to Cox regression analysis , the subjects in Clusters C ( hazard ratio (HR)=4.0 , 95 % confidence interval (CI)=1.1 - 15.1 ) and D ( HR=4.9 , 95 % CI=1.2 - 21.1 ) were at a significantly greater risk of pneumonia than those in Cluster A , independent of other confounding factors . Logistic regression analysis adjusting for the same covariates indicated that the number of subjects with more than 9 febrile days per year was significantly lower in Cluster A than in the other clusters . CONCLUSION The comprehensive microfloral profile of the tongue coating is closely related to pneumonia-related health problems in institutionalized older adults BACKGROUND Halitosis is a common problem in humans , and is a social and psychological h and icap for those affected by it . Halitosis has a positive correlation with the accumulation of bacterial plaque in the oral cavity . AIMS The aim of the present study was to determine the effect of tongue brushing on oral malodor in adolescents . METHODS The subjects of the investigation were 28 adolescents who had oral malodor and whose average age was 16 + /- 0.12 years . Subjects were chosen to participate in the study if they had an established routine of oral care , and did not have systemic or periodontal disease or dentures ( such as fixed prosthesis or partial and total dentures ) . The subjects with oral malodor were r and omly assigned into two groups . Individual Output:	Discussion : The use of toothbrushing plus tongue cleaning compared with toothbrushing alone significantly reduced the indicators of halitosis and TC . However , there is insufficient evidence to recommend frequency , duration , or delivery method of tongue cleaning .
MS22581	*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 Maternal glucose and lipid levels are associated with neonatal anthropometry of the offspring , also independently of maternal body mass index ( BMI ) . Gestational weight gain , however , is often not accounted for . The objective was to explore whether the effects of maternal glucose and lipid levels on offspring ’s birth weight and subcutaneous fat were independent of early pregnancy BMI and mid-gestational weight gain . Methods In a population -based , multi-ethnic , prospect i ve cohort of 699 women and their offspring , maternal anthropometrics were collected in gestational week 15 and 28 . Maternal fasting plasma lipids , fasting and 2-hour glucose post 75 g glucose load , were collected in gestational week 28 . Maternal risk factors were st and ardized using z-scores . Outcomes were neonatal birth weight and sum of skinfolds in four different regions . Results Mean ( st and ard deviation ) birth weight was 3491 ± 498 g and mean sum of skinfolds was 18.2 ± 3.9 mm . Maternal fasting glucose and HDL-cholesterol were predictors of birth weight , and fasting and 2-hour glucose were predictors of neonatal sum of skinfolds , independently of weight gain as well as early pregnancy BMI , gestational week at inclusion , maternal age , parity , smoking status , ethnic origin , gestational age and offspring ’s sex . However , weight gain was the strongest independent predictor of both birth weight and neonatal sum of skinfolds , with a 0.21 kg/week increased weight gain giving a 110.7 ( 95 % confidence interval 76.6 - 144.9 ) g heavier neonate , and with 0.72 ( 0.38 - 1.06 ) mm larger sum of skinfolds . The effect size of mother ’s early pregnancy BMI on birth weight was higher in non-Europeans than in Europeans . Conclusions Maternal fasting glucose and HDL-cholesterol were predictors of offspring ’s birth weight , and fasting and 2-hour glucose were predictors of neonatal sum of skinfolds , independently of weight gain . Mid-gestational weight gain was a stronger predictor of both birth weight and neonatal sum of skinfolds than early pregnancy BMI , maternal glucose and lipid levels BACKGROUND Compromised fetal growth may program chronic diseases of adulthood , and it has been suggested that maternal nutrition is a major determinant of fetal growth . We previously found no clinical ly significant associations between maternal diet and the size of the infant and placenta at birth in a large cohort of white women living in the United Kingdom . OBJECTIVE The objective was to examine the relations between indexes of maternal nutritional status in pregnancy and the birth and placental weights of infants born at term . DESIGN We conducted a prospect i ve cohort study of 798 white nulliparous women with singleton pregnancies . Blood sample s were obtained at approximately 16 and 28 wk of gestation . RESULTS The concentration of most nutrients was not associated with pregnancy outcome . High retinol and hemoglobin concentrations in late , but not in early , pregnancy were strongly and independently associated with lower birth weight and smaller placental size at birth . Each 0.1- micro mol increase in retinol predicted a 20.8-g ( 95 % CI : 9.2 , 32.5 g ) decrease in birth weight ( P < 0.001 ) , and each 0.1-g/L increase in hemoglobin predicted a 61.5-g ( 95 % CI : 28.5 , 94.4 g ) decrease in birth weight ( P < 0.001 ) . CONCLUSIONS We found negative associations between birth and placental weights and maternal retinol and hemoglobin concentrations . These relations may be causal or may reflect an underlying metabolic dysfunction , such as failure of plasma volume expansion . Our results provide no evidence that having high circulating nutrient concentrations , for example , through the use of supplements , would improve infant and placental growth CONTEXT Elevated lipid levels during late pregnancy are associated with complications and adverse outcome for both mother and newborn . However , it is inconclusive whether a disturbed lipid profile during early pregnancy has similar negative associations . OBJECTIVE Our objective was to investigate whether nonfasting maternal total cholesterol and triglyceride levels during early pregnancy are associated with six major adverse pregnancy outcomes . METHODS Data were derived from the Amsterdam Born Children and Their Development ( ABCD ) cohort study . R and om blood sample s of nonfasting total cholesterol and triglyceride levels were determined during early gestation ( median = 13 , interquartile range = 12 - 14 wk ) . Outcome measures were pregnancy-induced hypertension ( PIH ) , preeclampsia , preterm birth , small/large for gestational age ( SGA/LGA ) , and child loss . Only nondiabetic women with singleton deliveries were included ; the baseline sample consisted of 4008 women . Analysis for PIH and preeclampsia were performed in nulliparous women only ( n = 2037 ) . RESULTS Mean ( sd ) triglyceride and total cholesterol levels were 1.33 ( 0.55 ) and 4.98 ( 0.87 ) mmol/liter , respectively . The incidence of pregnancy complications and perinatal outcomes were as follows : PIH , 4.9 % ; preeclampsia , 3.7 % ; preterm birth , 5.3 % ; SGA , 9.3 % ; LGA , 9.3 % ; and child loss , 1.4 % . After adjustments , every unit increase in triglycerides was linearly associated with an increased risk of PIH [ odds ratio ( OR ) = 1.60 , P = 0.021 ] , preeclampsia ( OR = 1.69 , P = 0.018 ) , LGA ( OR = 1.48 , P < 0.001 ) , and induced preterm delivery ( OR = 1.69 , P = 0.006 ) . No associations were found for SGA or child loss . Total cholesterol was not associated with any of the outcome measures . CONCLUSIONS Elevated maternal triglyceride levels measured during early pregnancy are associated with pregnancy complications and adverse pregnancy outcomes . These results suggest that future lifestyle programs in women of reproductive age with a focus on lowering triglyceride levels ( i.e. diet , weight reduction , and physical activity ) may help to prevent hypertensive complications during pregnancy and adverse birth outcomes OBJECTIVE To investigate whether r and omly sample d maternal total cholesterol ( TC ) and triglycerides ( TG ) levels during early pregnancy are associated with birth weight ( BW ) and postnatal growth . STUDY DESIGN Data were derived from the prospect i ve Amsterdam Born Children and their Development cohort study . R and omly sample d TC and TG levels were determined in early gestation ( median , 13 ; IQR , 12 - 14 weeks ) . Outcome measures were BW SDS and weight-for-gestational age ; postnatal outcome measures were SDS in weight , length , and body mass index during the first year of life ( total n = 2502 ) . RESULTS The highest TG level was associated with a higher BW SDS ( differences 0.20 ± 0.06 between highest and middle quintile ; P = .002 ) and with a higher prevalence ( 13 % ) of an infant large for gestational age compared with middle quintile ( 9 % ; P = .04 ) . Infants from mothers in the lowest TG quintile had lower SDS in weight , length , and body mass index until age 3 months , and displayed accelerated postnatal growth patterns . Maternal TC was not associated with BW or postnatal growth . CONCLUSION High maternal TG levels in the first term of pregnancy were associated with higher BWs and subsequently a higher occurrence of infants large for gestational age , whereas low TG levels were associated with accelerated postnatal growth Objective To determine whether elevated midpregnancy maternal serum lipid levels predict newborn weight at term and the risk of large for gestational age ( LGA ) infants in women with positive diabetic screen but normal glucose tolerance test . Methods Japanese gravidas who had positive diabetic screens and normal 75-g oral glucose tolerance tests ( GTT ) at 24–32 weeks were enrolled . Subjects with complications , including diabetes , hypertension , or fetal anomalies were excluded , as were women with multifetal gestations . Fasting serum triglyceride , free fatty acids , and total cholesterol levels were measured at the time of GTT . We tested the association between maternal variables and birth weight by univariable analysis . We used multivariable analysis to test whether the association between fasting lipids and birth weight was independent of prepregnant maternal body mass index ( BMI ) , maternal weight gain during pregnancy , and plasma glucose levels at GTT . We also used multiple logistic regression analysis to determine whether maternal hyperlipidemia , defined as more than the 75th percentile of each lipid , is a risk factor for having an LGA infant . Results We enrolled 146 subjects . Among measured maternal lipids , only triglyceride levels correlated with birth weight in univariable analysis ( r = 0.22 , P = .009 ) . Birth weight also was correlated with prepregnant maternal BMI ( r = 0.18 , P = .04 ) and fasting plasma glucose levels ( r = 0.17 , P = .04 ) . The association between maternal fasting triglyceride level and birth weight remained significant after adjusting for prepregnant BMI , maternal weight gain , fasting plasma glucose levels , fetal gender , and gestational age at birth ( P = .01 ) . Logistic regression analysis showed that fasting maternal hypertriglyceridemia ( over 259 mg/dL ) was the significant predictor of LGA infants , independent of prepregnant BMI , maternal weight gain , and maternal plasma glucose levels ( odds ratio 11.6 ; 95 % confidence interval 1.1 , 122 ; P = .04 ) . Conclusion In women with positive diabetic screens but normal GTTs , fasting triglyceride levels at 24–32 weeks correlated positively with newborn weight at term , independent of maternal plasma glucose levels and obesity . Maternal fasting serum triglyceride levels in midpregnancy might be an independent predictor of fetal macrosomia in those women OBJECTIVE Factors associated with increasing maternal triglyceride concentrations in late pregnancy include gestational age , obesity , preeclampsia , and altered glucose metabolism . In a subgroup of women in the Metformin in Gestational Diabetes ( MiG ) trial , maternal plasma triglycerides increased more between enrollment ( 30 weeks ) and 36 weeks in those treated with metformin compared with insulin . The aim of this study was to explain this finding by examining factors potentially related to triglycerides in these women . RESEARCH DESIGN AND METHODS Of the 733 women r and omized to metformin or insulin in the MiG trial , 432 ( 219 metformin and 213 insulin ) had fasting plasma triglycerides measured at enrollment and at 36 weeks . Factors associated with maternal triglycerides were assessed using general linear modeling . RESULTS Mean plasma triglyceride concentrations were 2.43 ( 95 % CI 2.35–2.51 ) mmol/L at enrollment . Triglycerides were higher at 36 weeks in women r and omized to metformin ( 2.94 [ 2.80–3.08 ] mmol/L ; + 23.13 % [ 18.72–27.53 % ] ) than insulin ( 2.65 [ 2.54–2.77 ] mmol/L , P = 0.002 ; + 14.36 % [ 10.91–17.82 % ] , P = 0.002 ) . At 36 weeks , triglycerides were associated with HbA1c ( P = 0.03 ) , ethnicity ( P = 0.001 ) , and treatment allocation ( P = 0.005 ) . In insulin-treated women , 36-week triglycerides were associated with 36-week HbA1c ( P = 0.02 ) , and in metformin-treated women , they were related to ethnicity . CONCLUSIONS At 36 weeks , maternal triglycerides were related to glucose control in women treated with insulin and ethnicity in women treated with metformin . Whether there are ethnicity-related dietary changes or differences in metformin response that alter the relationship between glucose control and triglycerides requires further study Background : High maternal dietary intakes in pregnancy may lead to increased fetal growth and program neuroendocrine pathways that result in greater appetite , energy intake , and adiposity in offspring later in life . Few prospect i ve dietary studies have explored this relation . Objective : The objective was to assess associations of maternal dietary intake in pregnancy and maternal and paternal dietary intake postnatally with child dietary intake and adiposity . Design : Dietary intakes of energy , protein , total fat , and carbohydrate were assessed prospect ively in mothers during pregnancy , in mothers and their partners at 47 mo postnatally , and in children at 10 y ( n = 5717 mother-child pairs prenatally , 5593 mother-child pairs postnatally , and 300 Output:	RESULTS Data from 46 publications including 31,402 pregnancies suggest that maternal high triglycerides and low high-density-lipoprotein cholesterol levels throughout pregnancy are associated with increased birthweight , higher risk of large for gestational age and macrosomia and lower risk of small-for-gestational age . The findings were consistent across the studied population s , but stronger associations were observed in women who were overweight or obese prior to pregnancy .
MS22582	*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 . The efficacy of radiofrequency medial branch neurotomy to treat cervical zygapophysial joint pain from whiplash was compared prospect ively in litigants and nonlitigants . Objectives . 1 ) To assess the effect of monetary gain on treatment of zygapophysial joint pain in cervical whiplash . 2 ) To determine whether radiofrequency medial branch neurotomy is effective treatment for whiplash . Summary of Background Data . The influence of litigation on treatment outcome is a subject of controversy in both the medical and legal professions . This is the first study to examine this issue in a prospect i ve manner using a previously proven diagnostic and therapeutic method . Methods . Sixty patients with cervical whiplash who remained symptomatic after 20 weeks of conservative management were referred for radiofrequency cervical medial neurotomy . The patients were classified as litigant or nonlitigant based on whether the potential for monetary gain via litigation existed . Each group underwent identical evaluation and treatment . Patients were observed for 1 year . Visual analogue scores and self-reported improvement were obtained before , immediately after , and 1 year after radiofrequency cervical medial neurotomy . Results . Forty-six patients completed the study . The overall reduction in cervical whiplash symptoms and visual analogue pain scores were significant immediately after treatment ( nonlitigants vs. litigants : 2.0 vs. 2.5 , P = 0.36 ) and at 1 year ( nonlitigants vs. litigants : 2.9 vs. 4.0 , P = 0.05 ) . One-year follow-up scores were higher than immediate post-treatment scores ( nonlitigants vs. litigants : 2.5 vs. 3.6 ) . The difference between litigants and nonlitigants in the degree of symptomatology or response to treatment did not reach significance . Conclusions . These results demonstrate that the potential for secondary gain in patients who have cervical facet arthropathy as a result of a whiplash injury does not influence response to treatment . These data contradict the common notion that litigation promotes malingering . This study also confirms the efficacy of radiofrequency medial branch neurotomy in the treatment of traumatic cervical facet arthropathy STUDY DESIGN A prospect i ve audit . OBJECTIVE To establish the efficacy of lumbar medial branch neurotomy under optimum conditions . SUMMARY OF BACKGROUND DATA Previous reports of the efficacy of lumbar medial branch neurotomy have been confounded by poor patient selection , inaccurate surgical technique , and inadequate assessment of outcome . METHODS Fifteen patients with chronic low back pain whose pain was relieved by controlled , diagnostic medial branch blocks of the lumbar zygapophysial joints , underwent lumbar medial branch neurotomy . Before surgery , all were evaluated by visual analog scale and a variety of vali date d measures of pain , disability , and treatment satisfaction . Electromyography of the multifidus muscle was performed before and after surgery to ensure accuracy of the neurotomy . All outcome measures were repeated at 6 weeks , and 3 , 6 , and 12 months after surgery . RESULTS Some 60 % of the patients obtained at least 90 % relief of pain at 12 months , and 87 % obtained at least 60 % relief . Relief was associated with denervation of the multifidus in those segments in which the medial branches had been coagulated . Prelesion electrical stimulation of the medial branch nerve with measurement of impedance was not associated with outcome . CONCLUSIONS Lumbar medial branch neurotomy is an effective means of reducing pain in patients carefully selected on the basis of controlled diagnostic blocks . Adequate coagulation of the target nerves can be achieved by carefully placing the electrode in correct position as judged radiologically . Electrical stimulation before lesioning is superfluous in assuring correct placement of the electrode BACKGROUND Chronic pain in the cervical zygapohyseal joints is a common problem after whiplash injury , but treatment is difficult . Percutaneous radiofrequency neurotomy can relieve the pain by denaturing the nerves innervating the painful joint , but the efficacy of this treatment has not been established . METHODS In a r and omized , double-blind trial , we compared percutaneous radio-frequency neurotomy in which multiple lesions were made and the temperature of the electrode making the lesions was raised to 80 degrees C with a control treatment using an identical procedure except that the radio-frequency current was not turned on . We studied 24 patients ( 9 men and 15 women ; mean age , 43 years ) who had pain in one or more cervical zygapophyseal joints after an automobile accident ( median duration of pain , 34 months ) . The source of their pain had been identified with the use of double-blind , placebo-controlled local anesthesia . Twelve patients received each treatment . The patients were followed by telephone interviews and clinic visits until they reported that their pain had returned to 50 percent of the preoperative level . RESULTS The median time that elapsed before the pain returned to at least 50 percent of the preoperative level was 263 days in the active-treatment group and 8 days in the control group ( P=0.04 ) . At 27 weeks , seven patients in the active-treatment group and one patient in the control group were free of pain . Five patients in the active-treatment group had numbness in the territory of the treated nerves , but none considered it troubling . CONCLUSIONS In patients with chronic cervical zygapophyseal-joint pain confirmed with double-blind , placebo-controlled local anesthesia , percutaneous radio-frequency neurotomy with multiple lesions of target nerves can provide lasting relief STUDY DESIGN A prospect i ve double-blind r and omized trial in 31 patients . OBJECTIVES To assess the clinical efficacy of percutaneous radiofrequency denervation of the lumbar zygapophysial joints in reducing pain , functional disability , and physical impairment in patients with back pain originating from the lumbar zygapophysial joints . SUMMARY OF BACKGROUND DATA Chronic low back pain is a major health problem in the industrialized world . A treatment option is percutaneous radiofrequency denervation of the lumbar zygapophysial joints . Its clinical efficacy has never been formally tested in a controlled trial . METHODS Thirty-one patients with a history of at least 1 year of chronic low back pain were selected on the basis of a positive response to a diagnostic nerve blockade and subsequently r and omly assigned to one of two treatment groups . Each patient in the radiofrequency treatment group ( 15 patients ) received an 80 C radiofrequency lesion of the dorsal ramus of the segmental nerve roots L3 , L4 , and L5 . Patients in the control group ( n = 16 ) underwent an the same procedure but without use of a radiofrequency current . Both the treating physician and the patients were blinded to the group assignment . Before treatment , physical impairment , rating of pain , the degree of disability , and quality of life were assessed by a blinded investigator . RESULTS Eight weeks after treatment , there were 10 success patients in the radiofrequency group ( n = 15 ) and 6 in the sham group ( n = 16 ) . The unadjusted odds ratio was 3.3 ( P = 0.05 , not significant ) , and the adjusted odds ratio was 4.8 ( P < 0.05 , significant ) . The differences in effect on the visual analog scale scores , global perceived effect , and the Oswestry disability scale were statistically significant . Three , 6 , and 12 months after treatment , there were significantly more success patients in the radiofrequency group compared with the sham group . CONCLUSIONS Radiofrequency lumbar zygapophysial joint denervation results in a significant alleviation of pain and functional disability in a select group of patients with chronic low back pain , both on a short-term and a long-term basis OBJECTIVE The objective of this study was to determine the effectiveness of cervical medial branch radiofrequency neurotomy ( RFN ) performed by two practitioners trained according to rigorous guidelines . DESIGN The study was design ed as a prospect i ve , outcome study of consecutive patients with chronic neck pain treated in a community setting . INTERVENTIONS A total of 104 patients , selected on the basis of complete relief of pain following controlled , diagnostic , medial branch blocks , were treated with RFN according to the guidelines of the International Spine Intervention Society . OUTCOME MEASURES Successful outcome was defined as complete relief of pain , or at least 80 % relief , for at least 6 months , with complete restoration of activities of daily living , no need for any further health care , and return to work . Patients who failed to meet any of these criteria were deemed to have failed treatment . RESULTS In the two practice s , 74 % and 61 % of patients achieved a successful outcome . Relief lasted 17 - 20 months from the first RFN , and 15 months for repeat treatments . Allowing for repeat treatment , patients maintained relief for a median duration of 20 - 26 months , with some 60 % still having relief at follow-up . CONCLUSION Cervical RFN can be very effective when performed in a rigorous manner in appropriately selected patients . Chronic neck pain , mediated by the cervical medial branches , can be temporarily , but completely , relieved and patients fully restored to desired activities of daily living , if treated with RFN Facet joint pain is an important aspect of degenerative lumbar spine disease , and radiofrequency medial branch neurotomy remains an established therapy , while cryodenervation has still been poorly examined . This study was undertaken to examine the effects of medial branch cryodenervation in the treatment of lumbar facet joint pain . This was a prospect i ve clinical case series . Patient selection was based on the history , physical examination and positive medial branch blocks . Percutaneous medial branch cryodenervation was performed using a Lloyd Neurostat 2000 . Target parameters were low back pain ( VAS ) , limitation of activity ( McNab ) and overall satisfaction . Fifty patients were recruited , and 46 completed the study . The follow-up time was 1 year . At 6 weeks , 33 patients ( 72 % ) were pain free or had major improvement of low back pain ; 13 ( 28 % ) had no or little improvement . Including failures , mean low back pain decreased significantly from 7.7 preoperatively to 3.2 at 6 weeks , 3.3 at 3 months , 3.0 at 6 months and 4.2 at 12 months ( P<0.0001 ) . Limitation of the activities of daily living improved parallel to reduced pain . Our results suggest that medial branch cryodenervation is a safe and effective treatment for lumbar facet joint pain . RésuméBut de l’étude : les douleurs facétaires articulaires sont un élément important de la pathologie dégénérative de la colonne lombaire et la neurotomie par radio fréquence de la branche médiale est un traitement classique , alors que les résultats de la cryodénervation ne sont pas considérés comme évidents . Cette étude a pour but d’examiner les effets de la cryodénervation des rameaux médians dans le traitement des douleurs facétaires . L’étude a été menée de façon prospect i ve . Les patients ont été sélectionnés selon leur histoire , l’examen physique et la positivité de la réalisation d’une infiltration des rameaux médians . La cryodénervation par voie percutanée a été réalisée par un appareil Lyod Neurostat 2000 . Les paramètres étudiés ont été les lombalgies ( VAS ) , la limitation d’activité ( McNab ) et la satisfaction . Cinquante patients ont été recrutés pour ce traitement , 46 sujets ont été spécialement étudiés et suivis pendant au moins un an . Résultats : à 6 semaines , 33 patients ( 72 % ) ne présentent aucune douleur et ont une gr and e amélioration de leur lombalgie , 13 ( 28 % ) n’ont pas ou simplement ont une petite amélioration . Malgré les échecs , les douleurs lombaires diminuent de façon significative avec une échelle de 7.7 préopératoire à 3.2 à 6 semaines , de 3.3 à 3 mois , de 3.0 à 6 mois et 4.2 à 12 mois ( P<0.0001 ) . En conclusion , nous pouvons affirmer , aux vues de nos résultats que la cryodénervation des rameaux médians est un procédé donnant de bons résultats réguliers dans le traitement des syndromes facétaires douloureux Radiofrequency neurolysis of lumbar medial branch is currently the only proven way to treat patients with chronic lumbar zygapophysial joint pain , however , in some patients it can cause transient postoperative pain due to an inflammation caused by trauma of the electrode insertion and the thermal lesion around the target nerves . The aim of this study was to assess the effectiveness of intraoperative injection of methylprednisolone or pentoxifylline in comparison with placebo ( saline ) to prevent this process . 45 consecutive patients seen by one physician at one pain management clinic were included . Patients were r and omly assigned to 3 groups of 15 patients treated with radiofrequency neurotomy procedure with an addition of methylprednisolone , pentoxifylline or saline , respectively , and were observed for 6 months . Pain intensity , summed pain intensity difference , minimum 50 % reduction of pain intensity , Patients Satisfaction Score , and local tenderness were determined . The 50 % reduction of pain intensity was achieved in 80 % of patients one week after the procedure , and at 6 months such results were reported by 60 % of patients . There was a significant reduction of pain intensity in all three groups at Output:	Apart from soreness of the paravertebral muscles no severe side effects were encountered . Conclusion This is the first report of cryoneurolysis for the treatment of cervical facet joint pain .
MS22583	*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 Outcomes from out-of-hospital cardiac arrest ( OHCA ) may improve if rescuers perform chest compressions ( CCs ) deeper than the previous recommendation of 38 - 51 mm and consistent with the 2010 AHA Guideline recommendation of at least 51 mm . The aim of this study was to assess the relationship between CC depth and OHCA survival . METHODS Prospect i ve analysis of CC depth and outcomes in consecutive adult OHCA of presumed cardiac etiology from two EMS agencies participating in comprehensive CPR quality improvement initiatives . ANALYSIS Multivariable logistic regression to calculate adjusted odds ratios ( aORs ) for survival to hospital discharge and favorable functional outcome . RESULTS Among 593 OHCAs , 136 patients ( 22.9 % ) achieved return of spontaneous circulation , 63 patients ( 10.6 % ) survived and 50 had favorable functional outcome ( 8.4 % ) . Mean CC depth was 49.8±11.0 mm and mean CC rate was 113.9±18.1CCmin(-1 ) . Mean depth was significantly deeper in survivors ( 53.6 mm , 95 % CI : 50.5 - 56.7 ) than non-survivors ( 48.8 mm , 95 % CI : 47.6 - 50.0 ) . Each 5 mm increase in mean CC depth significantly increased the odds of survival and survival with favorable functional outcome : aORs were 1.29 ( 95 % CI 1.00 - 1.65 ) and 1.30 ( 95 % CI 1.00 - 1.70 ) respectively . CONCLUSION Deeper chest compressions were associated with improved survival and functional outcome following OHCA . Our results suggest that adhering to the 2010 AHA Guideline -recommended depth of at least 51 mm could improve outcomes for victims of OHCA Objective To investigate whether real-time audio and visual feedback during cardiopulmonary resuscitation outside hospital increases the proportion of subjects who achieved prehospital return of spontaneous circulation . Design A cluster-r and omised trial . Subjects 1586 people having cardiac arrest outside hospital in whom resuscitation was attempted by emergency medical services ( 771 procedures without feedback , 815 with feedback ) . Setting Emergency medical services from three sites within the Resuscitation Outcomes Consortium in the United States and Canada . Intervention Real-time audio and visual feedback on cardiopulmonary resuscitation ( CPR ) provided by the monitor-defibrillator . Main outcome measure Prehospital return of spontaneous circulation after CPR . Results Baseline patient and emergency medical service characteristics did not differ between groups . Emergency medical services muted the audible feedback in 14 % of cases during the period with feedback . Compared with CPR clusters lacking feedback , clusters assigned to feedback were associated with increased proportion of time in which chest compressions were provided ( 64 % v 66 % , cluster-adjusted difference 1.9 ( 95 % CI 0.4 to 3.4 ) ) , increased compression depth ( 38 v 40 mm , adjusted difference 1.6 ( 0.5 to 2.7 ) ) , and decreased proportion of compressions with incomplete release ( 15 % v 10 % , adjusted difference −3.4 ( −5.2 to −1.5 ) ) . However , frequency of prehospital return of spontaneous circulation did not differ according to feedback status ( 45 % v 44 % , adjusted difference 0.1 % ( −4.4 % to 4.6 % ) ) , nor did the presence of a pulse at hospital arrival ( 32 % v 32 % , adjusted difference −0.8 ( −4.9 to 3.4 ) ) , survival to discharge ( 12 % v 11 % , adjusted difference −1.5 ( −3.9 to 0.9 ) ) , or awake at hospital discharge ( 10 % v 10 % , adjusted difference −0.2 ( −2.5 to 2.1 ) ) . Conclusions Real-time visual and audible feedback during CPR altered performance to more closely conform with guidelines . However , these changes in CPR performance were not associated with improvements in return of spontaneous circulation or other clinical outcomes . Trial Registration Clinical Trials Objective : Guidelines for cardiopulmonary resuscitation recommend a chest compression rate of at least 100 compressions/min . A recent clinical study reported optimal return of spontaneous circulation with rates between 100 and 120/min during cardiopulmonary resuscitation for out-of-hospital cardiac arrest . However , the relationship between compression rate and survival is still undetermined . Design : Prospect i ve , observational study . Setting : Data is from the Resuscitation Outcomes Consortium Prehospital Resuscitation IMpedance threshold device and Early versus Delayed analysis clinical trial . Participants : Adults with out-of-hospital cardiac arrest treated by emergency medical service providers . Interventions : None . Measurements Main Results : Data were abstract ed from monitor-defibrillator recordings for the first five minutes of emergency medical service cardiopulmonary resuscitation . Multiple logistic regression assessed odds ratio for survival by compression rate categories ( < 80 , 80–99 , 100–119 , 120–139 , ≥140 ) , both unadjusted and adjusted for sex , age , witnessed status , attempted byst and er cardiopulmonary resuscitation , location of arrest , chest compression fraction and depth , first rhythm , and study site . Compression rate data were available for 10,371 patients ; 6,399 also had chest compression fraction and depth data . Age ( mean ± SD ) was 67 ± 16 years . Chest compression rate was 111 ± 19 per minute , compression fraction was 0.70 ± 0.17 , and compression depth was 42 ± 12 mm . Circulation was restored in 34 % ; 9 % survived to hospital discharge . After adjustment for covariates without chest compression depth and fraction ( n = 10,371 ) , a global test found no significant relationship between compression rate and survival ( p = 0.19 ) . However , after adjustment for covariates including chest compression depth and fraction ( n = 6,399 ) , the global test found a significant relationship between compression rate and survival ( p = 0.02 ) , with the reference group ( 100–119 compressions/min ) having the greatest likelihood for survival . Conclusions : After adjustment for chest compression fraction and depth , compression rates between 100 and 120 per minute were associated with greatest survival to hospital discharge OBJECTIVE Agonal breathing is present in up to 40 % of pre-hospital cardiac arrests and is commonly mistaken as a sign of circulation leading to omission of byst and er resuscitation . The aim of this study was to test the hypothesis that specific tuition on agonal breathing improves the accuracy of checking for signs of circulation as a diagnostic test for cardiac arrest . METHODS First year medical students were r and omised to control or intervention groups . The control group were taught st and ard CPR according to current guidelines . The intervention group received st and ard CPR training plus specific tuition on the characteristics of agonal breathing . Two weeks after initial training , the students ' ability to recognise cardiac arrest was tested using a simulated cardiac arrest victim demonstrating normal , absent or agonal breathing . Diagnostic accuracy , sensitivity and specificity for the decision to start CPR was calculated . RESULTS Sixty-four students were equally r and omised to intervention and control groups . The intervention group had greater diagnostic accuracy for cardiac arrest compared to the control group ( 90 % versus 78 % , P=0.03 ) . The intervention group were more likely to recognise cardiac arrest correctly and initiate CPR than the control group ( sensitivity 90 % versus 78 % , P=0.02 ) . The improved results were predominantly due to recognition that agonal breathing is a sign of cardiac arrest ( 75 % intervention group versus 43 % control group , P=0.01 ) . CONCLUSION This study demonstrates improved diagnostic accuracy and sensitivity of " checking for signs of circulation " by teaching CPR providers to recognise agonal breathing as a sign of cardiac arrest BACKGROUND Current international resuscitation guidelines for lay people rely on the assessment of " normal breathing " as a key sign of breathing and circulation . However , it is not known how accurately laypersons can discriminate between " normal " and " abnormal " breathing . The aim of this study was to test the ability of medical students to discriminate between simulated normal and abnormal breathing patterns and select the correct treatment . METHODS Six video clips of simulated breathing were recorded showing : normal ; abnormal -shallow , rapid , agonal ( obstructed and unobstructed airways ) ; or absent breathing . The clips were vali date d by three experienced emergency practitioners and then shown in a r and om order to 48 second-year medical students . For each clip observers were asked to indicate : " Is this patient breathing ? " ( yes-normal , yes-abnormal , no ) and " What action would you take ? " ( rescue breathing or recovery position ) . RESULTS All experts correctly identified the breathing type and agreed on an appropriate emergency action . Students identified normal breathing as : normal 61 % , abnormal 33 % and absent 6 % ; abnormal breathing as : normal 29 % , abnormal 61 % , absent 10 % ; and absent breathing as : normal 8 % , abnormal 6 % , absent 85 % . Correct actions were selected in 86 % during normal breathing , 51 % during abnormal breathing and 86 % during absent breathing . The sensitivity for observers correctly identifying normal from abnormal breathing was 60 % and specificity 75 % and for selecting the correct action was 42 % and 80 % , respectively . CONCLUSIONS Medical students were unable to identify normal breathing from abnormal breathing reliably result ing in a high number of inappropriate , potentially harmful actions . Further evaluation of the optimal method for assessing for signs of breathing and circulation is required Background : The 2010 international guidelines for cardiopulmonary resuscitation recently recommended an increase in the minimum compression depth from 38 to 50 mm , although there are limited human data to support this . We sought to study patterns of cardiopulmonary resuscitation compression depth and their associations with patient outcomes in out-of-hospital cardiac arrest cases treated by the 2005 guideline st and ards . Design : Prospect i ve cohort . Setting : Seven U.S. and Canadian urban regions . Patients : We studied emergency medical services treated out-of-hospital cardiac arrest patients from the Resuscitation Outcomes Consortium Epistry – Cardiac Arrest for whom electronic cardiopulmonary resuscitation compression depth data were available , from May 2006 to June 2009 . Measurements : We calculated anterior chest wall depression in millimeters and the period of active cardiopulmonary resuscitation ( chest compression fraction ) for each minute of cardiopulmonary resuscitation . We controlled for covariates including compression rate and calculated adjusted odds ratios for any return of spontaneous circulation , 1-day survival , and hospital discharge . Main Results : We included 1029 adult patients from seven U.S. and Canadian cities with the following characteristics : Mean age 68 yrs ; male 62 % ; byst and er witnessed 40 % ; byst and er cardiopulmonary resuscitation 37 % ; initial rhythms : Ventricular fibrillation/ventricular tachycardia 24 % , pulseless electrical activity 16 % , asystole 48 % , other nonshockable 12 % ; outcomes : Return of spontaneous circulation 26 % , 1-day survival 18 % , discharge 5 % . For all patients , median compression rate was 106 per minute , median compression fraction 0.65 , and median compression depth 37.3 mm with 52.8 % of cases having depth < 38 mm and 91.6 % having depth < 50 mm . We found an inverse association between depth and compression rate ( p < .001 ) . Adjusted odds ratios for all depth measures ( mean values , categories , and range ) showed strong trends toward better outcomes with increased depth for all three survival measures . Conclusions : We found suboptimal compression depth in half of patients by 2005 guideline st and ards and almost all by 2010 st and ards as well as an inverse association between compression depth and rate . We found a strong association between survival outcomes and increased compression depth but no clear evidence to support or refute the 2010 recommendations of > 50 mm . Although compression depth is an important component of cardiopulmonary resuscitation and should be measured routinely , the most effective depth is currently unknown . ( Crit Care Med 2012 ; 40:–1198 OBJECTIVE To evaluate smartphone apps intended for self-management of pain using quality assessment criteria and usability testing with prospect i ve users . DESIGN 1 ) Survey and content analysis of available apps ; and 2 ) individual usability study of two apps . SETTING University of Leeds , United Kingdom . PARTICIPANTS Forty-one participants ( aged 19 - 59 years ) with experience of chronic or recurrent pain episodes . METHODS We undertook a survey , content analysis , and quality appraisal of all currently available mobile phone apps for self-management of pain . Two apps were then selected and assessed with usability testing . RESULTS Twelve apps met the inclusion criteria . The quality assessment revealed wide variation in their clinical content , interface design , and usability to support self-management of pain . Very little user or clinician involvement was identified in the development of the apps . From the usability testing , participants stated a preference for an interface design employing a lighter color scheme and particular text font . Although very few participants were aware of pain-reporting apps prior to participation , many would consider use in the future . CONCLUSIONS Variation in app quality and Output:	This is of exceptional importance for apps dealing with the treatment of life-threatening events such as cardiac arrest
MS22584	*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 : Oral propranolol reduces retinopathy of prematurity ( ROP ) progression , although not safely . This study evaluated safety and efficacy of propranolol eye micro-drops in preterm newborns with ROP . Methods : A multicenter open-label trial , planned according to the Simon optimal two-stage design , was performed to analyze safety and efficacy of propranolol micro-drops in newborns with stage 2 ROP . To this end , hemodynamic and respiratory parameters were monitored , and blood sample s were collected weekly , for 3 wk . Propranolol plasma levels were also monitored . The progression of the disease was evaluated with serial ophthalmologic examinations . Results : Twenty-three newborns were enrolled . Since the fourth of the first 19 newborns enrolled in the first stage of the study showed a progression to stage 2 or 3 with plus , the second stage was prematurely discontinued . Even though the objective to complete the second stage was not achieved , the percentage of ROP progression ( 26 % ) was similar to that obtained previously with oral propranolol administration . However , no adverse effects were observed and propranolol plasma levels were significantly lower than those measured after oral administration . Conclusion : Propranolol 0.1 % eye micro-drops are well tolerated , but not sufficiently effective . Further studies are required to identify the optimal dose and administration schedule 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 Our goals were to determine the mortality risk for infants weighing 501 to 1500 gm according to gestational age , birth weight , and gender and to document birth weight-related changes in mortality and morbidity over a 5-year time period . STUDY DESIGN In this observational study perinatal data were prospect ively collected by the 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network from May 1991 through December 1992 and compared with the corresponding data from 1987 through 1990 . St and ard definitions were used to record sociodemographic factors , perinatal events , and the neonatal course to 120 days of life , discharge , or death . RESULTS The 1991 and 1992 cohort included 4279 in-born infants . Among their mothers 10 % were < 18 years old ; 55 % were black , 31 % were white , and 11 % were Hispanic ; 14 % had received no prenatal care ; and 20 % had received antenatal corticosteroids . Multiple gestations accounted for 20 % of the births . Fifty percent of the infants were delivered by cesarean section . During 1991 and 1992 the overall survival for infants weighing 501 to 1500 gm at birth was 81 % , compared with 74 % in 1987 and 1988 . Survival at birth weight 501 to 750 gm was 44 % ; it was 81 % at 751 to 1000 gm , 92 % at 1001 to 1250 gm , and 95 % between 1251 and 1500 gm . Female infants had a significantly greater chance of surviving than male infants at similar birth weights and gestational ages . At any given gestational age , smaller infants were less likely to survive . Survival in all birth weight categories increased between 1987 and 1992 , without accompanying increases in medical morbidity . Major morbidity increased with decreasing birth weight and included late-onset septicemia 22 % , chronic lung disease ( oxygen dependence at 36 weeks ' corrected age ) 18 % , severe intraventricular hemorrhage ( grade s III and IV ) 11 % , and necrotizing enterocolitis 5 % . Twelve percent of all infants were treated with corticosteroids for chronic lung disease , including 36 % of infants who were oxygen dependent at age 28 days . The mean length of hospital stay was 69 days for survivors and 18 days for infants who died . CONCLUSIONS Mortality for infants between 501 and 1500 gm at birth has declined over the past 5 years . There are interactions between birth weight , gestational age , gender , and survival rate . This increase in survival was not accompanied by an increase in medical morbidity PURPOSE To examine the relationship between the intake of sugar inositol , serum inositol levels , and ROP in three groups of low birthweight infants receiving feedings containing various concentrations of inositol . METHODS Infants with a birthweight < 1500 g , with severe lung disease , were eligible for the study when they began enteral feedings . Infant formulas contained three different inositol concentrations : 2500 , 710 , and 242 micromol/L. Serum inositol concentrations were averaged over specific time intervals . A logistic regression model was used to investigate the confounding effect of duration of mechanical ventilation and oxygen therapy , birthweight , Apgar score , and serum inositol concentration on development of ROP . RESULTS Infants receiving high inositol formula and with higher serum inositol concentrations at birth and after 30 days had a statistically significant lower incidence of severe ROP than those receiving the lower inositol formula and with lower serum concentrations ( P<.05 ) . The effective serum inositol concentration ( EC90 ) associated with lesser disease was > 215 micromol/L. By logistic regression , the odds of developing severe ROP were greater among infants with low serum inositol concentration ( odds ratio=4.7 , 95 % confidence interval 0.90 - 24.8 , P=.017 ) . CONCLUSION Inositol supplementation may help prevent the most severe form of ROP According to preliminary results inositol ( INO ) is an important nutrient to immature preterm infants ( J Pediatr 1987 ; 110:604 ) . However , it is absent in nutrition of critically ill very low birth weight infants . In a present r and omized double blind trial INO or glucose ( 70–100 mg/kg/day ) was given to altogether 230 preterm infants ( gestation 24 to 31 w , mean 27.8 w , mean BW 1,106 g ) with RDS during 5 neonatal days . Two more courses during the first month were given , if the infant remained respirator-dependent and did not tolerate breast milk . INO-supplemented infants tended to have a milder respiratory course during the first week than those on glucose . The surviving INO-treated infants had a lower incidence of bronchopulmonary dysplasia ( BPD ) than the controls ( p<0.01 ) . No infant receiving INO had severe retinopathy ( gr 4 ) , whereas of the surviving placebo treated infants 8.8 % became blind ( p<0.005 ) . Inositol promotes endothelial cell growth , enhances glucocorticoid-mediated lung epithelial cell differentiation , and may serve as an antioxidant . INO should be seriously considered as a nutrient during compromised neonatal transition of very low birth weight infants Background : Preterm infants with respiratory distress syndrome ( RDS ) given inositol had reduced bronchopulmonary dysplasia ( BPD ) , death and severe retinopathy of prematurity ( ROP ) . We assessed the safety and pharmacokinetics of daily inositol to select a dose providing serum levels previously associated with benefit , and to learn if accumulation occurred when administered throughout the normal period of retinal vascularization . Methods : Infants ≤ 29 wk GA ( n = 122 , 14 centers ) were r and omized and treated with placebo or inositol at 10 , 40 , or 80 mg/kg/d . Intravenous administration converted to enteral when feedings were established , and continued to the first of 10 wk , 34 wk postmenstrual age ( PMA ) or discharge . Serum collection employed a sparse sampling population pharmacokinetics design . Inositol urine losses and feeding intakes were measured . Safety was prospect ively monitored . Results : At 80 mg/kg/d mean serum levels reached 140 mg/l , similar to Hallman ’s findings . Levels declined after 2 wk , converging in all groups by 6 wk . Analyses showed a mean volume of distribution 0.657 l/kg , clearance 0.058 l/kg/h , and half-life 7.90 h. Adverse events and comorbidities were fewer in the inositol groups , but not significantly so . Conclusion : Multiple dose inositol at 80 mg/kg/d was not associated with increased adverse events , achieves previously effective serum levels , and is appropriate for investigation in a phase III trial OBJECTIVES Our purpose was to determine the mortality and morbidity rates for infants weighing 501 to 1500 g according to gestational age , birth weight , and gender . STUDY DESIGN Perinatal data were collected prospect ively on an inborn cohort from January 1993 through December 1994 by 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network and were compared with the corresponding data from previous reports . Sociodemographic factors , perinatal events , and the neonatal course to 120 days of life , discharge , or death were evaluated . RESULTS Eighty-three percent of infants survived until discharge to home or to a long- term care facility ( compared with 74 % in 1988 ) . Survival to discharge was 49 % for infants weighing 501 to 750 g at birth , 85 % for those 751 to 1000 g , 93 % for those 1001 to 1250 g , and 96 % for those 1251 to 1500 g. The majority of deaths occurred within the first 3 days of life . Mortality rates were greater for male than for female infants . Respiratory distress syndrome was the most frequent pulmonary disease ( 52 % ) . Chronic lung disease ( defined as an oxygen requirement at 36 weeks after conception ) developed in 19 % . Thirty-two percent of infants had evidence of intracranial hemorrhage . Periventricular leukomalacia was noted in 6 % of infants who had ultrasonography after 2 weeks . The average duration of hospitalization for survivors was 68 days ( 122 days for surviving infants weighing 501 to 750 g , compared with an average of 43 days for surviving infants 1251 to 1500 g ) . Among infants who died , the average length of stay was 19 days . CONCLUSIONS The mortality rate for infants weighing between 501 and 1500 g at birth continues to decline . This increase in survival is not accompanied by an increase in medical morbidity . There are interactions between birth weight , gestational age , sex , and survival rates Objectives To evaluate the implementation of four high evidence practice s for the care of very preterm infants to assess their use and impact in routine clinical practice and whether they constitute a driver for reducing mortality and neonatal morbidity . Design Prospect i ve multinational population based observational study . Setting 19 regions from 11 European countries covering 850 000 annual births participating in the EPICE ( Effective Perinatal Intensive Care in Europe for very preterm births ) project . Participants 7336 infants born between 24 + 0 and 31 + 6 weeks ’ gestation in 2011/12 without serious congenital anomalies and surviving to neonatal admission . Main outcome measures Combined use of four evidence based practice s for infants born before 28 weeks ’ gestation using an “ all or none ” approach : delivery in a maternity unit with appropriate level of neonatal care ; administration of antenatal corticosteroids ; prevention of hypothermia ( temperature on admission to neonatal unit ≥36 ° C ) ; surfactant used within two hours of birth or early nasal continuous positive airway pressure . Infant outcomes were in-hospital mortality , severe neonatal morbidity at discharge , and a composite measure of death or severe morbidity , or both . We modelled associations using risk ratios , with propensity score weighting to account for potential confounding bias . Analyses were adjusted for clustering within delivery hospital . Results Only 58.3 % ( n=4275 ) of infants received all evidence based practice s for which they were eligible . Infants with low gestational age , growth restriction , low Apgar scores , and who were born on the day of maternal admission to hospital were less likely to receive evidence based care . After adjustment , evidence based care was associated with lower in-hospital mortality ( risk ratio 0.72 , 95 % confidence interval 0.60 to 0.87 ) and in-hospital mortality or severe morbidity , or both ( 0.82 , 0.73 to 0.92 ) , corresponding to an estimated 18 % decrease in all deaths without an increase in severe morbidity if these interventions had been provided to all infants . Conclusions More comprehensive use of evidence based practice s in perinatal medicine could result in considerable gains for very preterm infants , in terms of increased survival without severe morbidity PURPOSE To analyze the incidence and severity of retinopathy of prematurity ( ROP ) in China , and to explore Output:	Conclusions Based on current evidence , inositol supplementation showed no significant effect on preventing severe ROP , and exploratory sensitivity analysis showed a trend toward an increase on mortality
MS22585	*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 test the hypothesis that oral creatine supplements with exercise are more effective than exercise alone in improving muscle function in patients with established dermatomyositis or polymyositis receiving chronic medical therapies who are clinical ly weak yet stable . METHODS In a 6-month , 2-center , double-blind , r and omized controlled trial , patients were r and omized to receive oral creatine supplements ( 8 days , 20 gm/day then 3 gm/day ) or placebo . All patients followed a home exercise program . The primary outcome was aggregate functional performance time ( AFPT ) , reflecting the ability to undertake high-intensity exercise . Secondary outcomes included a functional index measuring endurance and muscle bioenergetics on (31)P magnetic resonance spectroscopy ( (31)P MRS ) . Patients were receiving stable immunosuppressive treatment and /or corticosteroids . RESULTS A total of 37 patients with polymyositis or dermatomyositis were r and omized ( 19 to creatine , 18 to placebo ) ; 29 completed 6 months . Intent-to-treat analyses demonstrated that AFPT improved significantly at 6 months with creatine ( median decrease 13 % , range -32 - 8 % ) compared with placebo ( median decrease 3 % , range -13 - 16 % ; P = 0.029 by Mann-Whitney U test ) . A completer analysis also showed significant benefits from creatine ( P = 0.014 ) . The functional index improved significantly with both creatine and placebo ( P < 0.05 by paired Wilcoxon 's rank sum test ) , with a significant benefit between groups in the completer analysis only . Phosphocreatine/beta-nucleoside triphosphate ratios using MRS increased significantly in the creatine group ( P < 0.05 ) but not in the control group . No clinical ly relevant adverse events were associated with creatine . CONCLUSION Oral creatine supplements combined with home exercises improve functional performance without significant adverse effects in patients with polymyositis or dermatomyositis . They appear safe , effective , and inexpensive BACKGROUND The therapeutic options for patients with polymyositis or dermatomyositis that is resistant to corticosteroids are limited , unproved , and often toxic . Uncontrolled trials concluded that both plasma exchange and leukapheresis are beneficial , but despite the considerable use of these approaches , proof of their efficacy is lacking . METHODS Thirty-nine patients with definite polymyositis or dermatomyositis were r and omly assigned to receive plasma exchange ( replacement of one volume of plasma with 5 percent albumin in saline ) , leukapheresis ( removal of 5 x 10(9 ) to 10 x 10(9 ) lymphocytes ) , or sham apheresis in a double-blind manner , with 12 treatments given over a one-month period . Muscle strength , functional capacity , and serum levels of muscle-associated enzymes were measured before and after the 12 procedures . RESULTS In each group 3 of 13 patients had improvements in strength and functional capacity . The condition of 3 patients treated with leukapheresis and 1 treated with plasma exchange deteriorated , and it was unchanged in the other 26 patients . Adverse effects of apheresis included the need for a central venous catheter ( 9 patients ) , major vasovagal episodes ( 3 patients ) , and severe citrate reactions ( 2 patients ) . Despite the occurrence of significant reductions in the serum levels of muscle enzymes with plasma exchange ( P less than 0.001 ) and significant decreases in lymphocyte counts with leukapheresis ( P = 0.002 ) , there were no significant differences among the three treatment groups in the final muscle strength or functional capacity of the patients . CONCLUSIONS As treatments for corticosteroid-resistant polymyositis or dermatomyositis , leukapheresis and plasma exchange are no more effective than sham apheresis BACKGROUND Dermatomyositis is a clinical ly distinct myopathy characterized by rash and a complement-mediated microangiopathy that results in the destruction of muscle fibers . In some patients the condition becomes resistant to therapy and causes severe physical disabilities . METHODS We conducted a double-blind , placebo-controlled study of 15 patients ( age , 18 to 55 years ) with biopsy-proved , treatment-resistant dermatomyositis . The patients continued to receive prednisone ( mean daily dose , 25 mg ) and were r and omly assigned to receive one infusion of immune globulin ( 2 g per kilogram of body weight ) or placebo per month for three months , with the option of crossing over to the alternative therapy for three more months . Clinical response was gauged by assessing muscle strength , neuromuscular symptoms , and changes in the rash . Changes in immune-mediated muscle abnormalities were determined by repeated muscle biopsies . RESULTS The eight patients assigned to immune globulin had a significant improvement in sores of muscle strength ( P < 0.018 ) and neuromuscular symptoms ( P < 0.035 ) , whereas the seven patients assigned to placebo did not . With crossovers a total of 12 patients received immune globulin . Of these , nine with severe disabilities had a major improvement to nearly normal function . Their mean muscle-strength scores increased from 74.5 to 84.7 , and their neuromuscular symptoms improved . Two of the other three patients had mild improvement , and one had no change in his condition . Of 11 placebo-treated patients , none had a major improvement , 3 had mild improvement , 3 had no change in their condition , and 5 had worsening of their condition . Repeated biopsies in five patients of muscles whose strength improved to almost normal showed an increase in muscle-fiber diameter ( P < 0.04 ) , an increase in the number and a decrease in the diameter of capillaries ( P < 0.01 ) , resolution of complement deposits on capillaries , and a reduction in the expression of intercellular adhesion molecule 1 and major-histocompatibility-complex class I antigens . CONCLUSIONS High-dose intravenous immune globulin is a safe and effective treatment for refractory dermatomyositis Polymyositis ( PM ) , dermatomyositis ( DM ) , and inclusion body myositis ( IBM ) are acquired inflammatory muscle disorders of unknown etiology that are currently classified under the rubric of idiopathic inflammatory myopathy ( IIM ) . All forms of IIM are characterized clinical ly by muscle weakness and pathologically by chronic muscle inflammation , although systemic manifestations involving many organ systems are common . Clinical subgroups have been recognized for many years and include adult-onset and juvenile-onset forms of PM and DM , myositis associated with another connective tissue disorder or malignancy , and the more recently recognized entity termed inclusion body myositis ( 1,2 ) . The presence of characteristic cutaneous features such as Gottron ’s papules and sign or the classic heliotrope rash distinguish DM from PM , and skin lesions may dominate the clinical presentation in some instances . Although the IIMs are rare diseases with an estimated incidence of 10 cases per million per year ( 3 ) , they are associated with substantial morbidity and mortality . Currently available treatment of IIM is unsatisfactory . Corticosteroids are the only agents approved by the US Food and Drug Administration ( FDA ) for myositis . However , anecdotal reports and reports of case series do support the use of other immunosuppressive agents such as methotrexate and azathioprine in the treatment of myositis . Because of the rarity and heterogeneity of IIM , there is a paucity of controlled prospect i ve clinical trials , and most published studies are from single referral centers reporting retrospectively on small numbers of patients followed up for relatively brief periods of time . Furthermore , accurate assessment of the effects of therapeutic interventions in IIM has been hampered by unreliable and insensitive outcome measures , as well as the challenge of distinguishing active and reversible disease from irreversible damage to muscle and other organs . Although previously published trials have utilized predefined outcome measures , no uniform criteria have been used to guide the conduct of these trials . As a result , different inclusion and exclusion criteria , trial duration , frequency of assessment s , concomitant therapies , safety monitoring procedures , outcome measures , definitions of responses and disease flares , and stratifications of patients at outcome analysis have been used in almost all trials . Thus , it has been difficult to compare results from any two myositis trials even when the same agent is being studied , result ing in the current uncertainty regarding the safety and efficacy of most agents To determine if high-dose pulsed dexamethasone is more effective and safer than daily high-dose prednisolone in treatment-naive adult patients with inflammatory myopathies ( sporadic inclusion body myositis excluded ) we performed a multicenter , double-blind r and omised controlled clinical trial with 18 months follow-up . Sixty-two patients were r and omised into 28-day cycles of oral high-dose dexamethasone or daily high-dose prednisolone . Primary outcome measures included ( 1 ) seven point composite score of six clinical ly relevant outcomes and ( 2 ) ( time-to ) remission and ( time-to ) relapse . No difference between both treatment groups on the composite score was found . Side-effects occurred significantly less frequently in the dexamethasone group . Median time to relapse was 60 ( 2.9 ) weeks in the prednisolone and 44 ( 4.7 ) weeks in the dexamethasone group ( log-rank test p=0.03 ) . In conclusion , pulsed high-dose oral dexamethasone is not superior to daily prednisolone as first-line treatment of idiopathic inflammatory myopathies , but is a good alternative by causing substantially fewer side-effects Two groups of patients with polymyositis have been followed for approximately 3 years . One group was treated with prednisone alone and the other with prednisone plus azathioprine . Although the polymyositis of both groups has improved , no statistically significant difference was noted at the end of 3 months , as previously reported . Longer followup , however , has shown that the group given prednisone plus azathioprine has improved more with respect to functional disability ; this group also requires less prednisone for disease control A controlled , prospect i ve , double-blind , therapeutic trial of azathioprine was conducted in the initial therapy of polymyositis . Sixteen patients received 60 mg prednisone per day plus either azathioprine ( 2 mg/kg of body weight per day ) or placebo for a period of 3 months . Creatine phosphokinase ( CPK ) levels fell to normal slightly sooner in the placebo group , but not significantly so . The azathioprine group did not become significantly stronger ( P = 0.58 ) and did not manifest significantly greater improvement of histopathologic features of muscle ( P = 0.80 ) than the placebo group . Initial CPK elevations were significantly related to the degree of muscle inflammation ( P = 0.037 ) , but this was not the case at 3 months ( P greater than 0.05 ) . Normalization of the CPK could not be equated with disease control . Type II fiber atrophy , attributed to steroid therapy , was more marked in women than in men ( P less than 0.03 ) OBJECTIVE To assess the safety and efficacy of rituximab in a r and omized , double-blind , placebo-phase trial in adult and pediatric myositis patients . METHODS Adults with refractory polymyositis ( PM ) and adults and children with refractory dermatomyositis ( DM ) were enrolled . Entry criteria included muscle weakness and ≥2 additional abnormal values on core set measures ( CSMs ) for adults . Juvenile DM patients required ≥3 abnormal CSMs , with or without muscle weakness . Patients were r and omized to receive either rituximab early or rituximab late , and glucocorticoid or immunosuppressive therapy was allowed at study entry . The primary end point compared the time to achieve the International Myositis Assessment and Clinical Studies Group preliminary definition of improvement ( DOI ) between the 2 groups . The secondary end points were the time to achieve ≥20 % improvement in muscle strength and the proportions of patients in the early and late rituximab groups achieving the DOI at week 8 . RESULTS Among 200 r and omized patients ( 76 with PM , 76 with DM , and 48 with juvenile DM ) , 195 showed no difference in the time to achieving the DOI between the rituximab late ( n = 102 ) and rituximab early ( n = 93 ) groups ( P = 0.74 by log rank test ) , with a median time to achieving a DOI of 20.2 weeks and 20.0 weeks , respectively . The secondary end points also did not significantly differ between the 2 treatment groups . However , 161 ( 83 % ) of the r and omized patients met the DOI , and individual CSMs improved in both groups throughout the 44-week trial . CONCLUSION Although there were no significant differences in the 2 treatment arms for the primary and secondary end points , 83 % of adult and juvenile myositis patients with refractory disease met the DOI . The role of B cell-depleting therapies in myositis warrants further study , with consideration for a different trial design OBJECTIVE To determine the effectiveness and tolerance of treatment with cyclosporine A ( CyA ) or methotrexate ( MTX ) added to corticosteroids in patients with severe , active polymyositis ( PM ) and dermatomyositis ( DM ) . PATIENTS AND METHODS Thirty-six patients ( 20 with DM , 16 with PM ) Output:	The fourth study comparing pulsed oral dexamethasone with daily oral prednisolone and found that the dexamethasone regime had a shorter median time to relapse but fewer side effects . Immunosuppressants were associated with significant side effects . AUTHORS ' CONCLUSIONS This systematic review highlights the lack of high quality RCTs that assess the efficacy and toxicity of immunosuppressants in inflammatory myositis
MS22586	*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 : To evaluate the usefulness of dynamic and delayed magnetic resonance ( MR ) imaging in the T-staging of stomach cancer and to compare the enhancement pattern of the cancerous lesion and the normal wall . Methods : We performed MR imaging in 46 patients with stomach cancer ( including four early gastric cancers and 42 advanced gastric cancers ) . Axial , sagittal , or coronal two-dimensional fast low-angle shot ) MR images for the water-distended stomach were obtained with dynamic protocol , including precontrast images and images obtained 30 , 60 , 90 , and 240–300 s after intravenous injection of the 0.1 mM Gd-DTPA/kg solution . We evaluated the thickness , interruption ( or not ) of the low signal intensity b and s , and enhancement pattern of the cancerous wall and normal gastric wall . We prospect ively evaluated the depth of cancer invasion , perigastric infiltration ( extraserosal invasion ) , perigastric organ invasion , and regional lymph nodes and determined tumor staging on MR images . These MR evaluations including MR-determined staging were correlated with the surgicopathologic findings . Results : Stomach cancer was shown as having a thickened wall with a rapid enhancing pattern after intravenous Gd-DTPA administration . The mucosa ( and /or submucosa ) affected by stomach cancer showed an early enhancement pattern ( 30–90 s after Gd-DTPA administration ) in 43 of 46 patients ( 93 % ) . The normal gastric mucosa demonstrated a delayed peak enhancement pattern ( > 90 s after Gd-DTPA administration ) in 29 of 46 patients ( 63 % ) and variable enhancement pattern in 17 of 46 patients ( 37 % ) . An interrupted low signal intensity b and or highly enhanced tumorous lesion penetrating through the gastric wall was seen in 17 of 19 pT3 patients ( 90 % ) . Consistency between MR-determined staging and surgicopathologic staging occurred in three of four pT1 tumors ( 75 % ) , 10 of 13 pT2 tumors ( 77 % ) , 17 of 19 pT3 tumors ( 90 % ) , and eight of 10 pT4 tumors ( 80 % ) ; overall accuracy was 83 % . Overall accuracy of regional lymph node involvement , as determined by enhanced MR , was 52 % ; 24 of 46 node groups were positive . Conclusions : Dynamic and delayed MR imaging can be useful for predicting depth of cancer invasion , perigastric infiltration ( extraserosal invasion ) , and perigastric organ invasion by gastric cancer Objective To determine the accuracy of the preoperative staging of uterine cervical cancer by magnetic resonance ( MR ) imaging in 115 patients in a prospect i ve study . Methods A prospect i ve study was performed in 115 patients who underwent MR imaging at 1.5 T before surgery or biopsy . Histopathologic findings were correlated with MR imaging results for all patients . Results The accuracy of preoperative tumor staging by MR imaging in the 115 patients was 77 % . In terms of the evaluation of parametrial status , this study had an accuracy of 94 % and a sensitivity of 38 % . The accuracy and sensitivity of MR imaging for vaginal invasion were 81 % and 87 % , respectively . In terms of lymph node metastasis , this study had an accuracy of 97 % and a sensitivity of 36 % . Conclusion Magnetic resonance imaging has high accuracy in the preoperative staging of uterine cervical cancer PURPOSE To assess magnetic resonance ( MR ) imaging in depicting the depth of myometrial infiltration , cervical invasion , and presence of enlarged lymph nodes in patients with endometrial adenocarcinoma compared with surgicopathologic findings . MATERIAL S AND METHODS Thirty-seven consecutive patients with endometrial carcinoma were included in this prospect i ve study . All patients underwent MR imaging and surgery . Qualitative image analysis included the depth of myometrial infiltration , infiltration of the uterine cervix , and presence of enlarged lymph nodes . Quantitative image analysis included tumor and myometrium contrast-to-noise ratios during different phases of dynamic imaging . MR imaging findings were compared with surgicopathologic findings . Sensitivity , specificity , diagnostic accuracy , and positive and negative predictive values of MR imaging in depicting myometrial and cervical infiltration and in lymph node assessment were calculated . RESULTS Respective sensitivity , specificity , diagnostic accuracy , and positive and negative predictive values in assessing myometrial infiltration were 87 % , 91 % , 89 % , 87 % , and 91 % ; those for cervical infiltration , 80 % , 96 % , 92 % , 89 % , and 93 % ; and those for lymph node assessment , 50 % , 95 % , 90 % , 50 % , and 95 % . There was significant agreement between MR imaging and surgicopathologic findings in assessment of myometrial invasion ( P < .001 ) . Myometrial and cervical invasion and lymph node enlargement were correctly assessed with MR imaging in 28 ( 76 % ) of 37 patients . Quantitative analysis showed a significant improvement in tumor and myometrium contrast-to-noise ratios during the equilibrium phase compared with the arterial and precontrast phases ( P < .001 ) . CONCLUSION MR imaging coupled with contrast material -enhanced dynamic MR imaging is highly accurate in local-regional staging of endometrial carcinoma ; more challenging is the assessment of pelvic and lumboaortic lymph nodes PURPOSE To evaluate the accuracy of a non-invasive " all-in-one " staging MR method in patients with pancreatic tumors . MATERIAL AND METHODS 46 patients were prospect ively evaluated by a combined MR imaging protocol including breath-hold T1- and T2-weighted pulse sequence , MRCP using a breath-hold 2D-RARE sequence , and breath-hold gadolinium-enhanced dual-phase 3D-MR angiography . RESULTS All pancreatic tumors were detected by the combination of cross-sectional imaging and MRCP . In spite of the use of MRCP , definitive differentiation between pancreatic carcinoma and chronic pancreatitis was not possible in 3 ( 6.5 % ) out of 46 cases . High quality 3D-MR angiograms were obtained in 43 ( 93.5 % ) cases . In 6 ( 13 % ) patients 3D-MRA showed an aberrant right hepatic artery . The overall accuracy of MRI in assessing extrapancreatic tumor spread , lymph node metastases , liver metastases , and vascular involvement was 95.7 % , 80.4 % , 93.5 % , and 89.1 % , respectively . CONCLUSION Due to its high accuracy , the " all-in-one " MR protocol may become the most important modality after clinical examination and ultrasound in the diagnostic work-up for most patients with suspicion of pancreatic tumors BACKGROUND In patients with prostate cancer who are deemed to be at intermediate or high risk of having nodal metastases , invasive diagnostic pelvic lymph-node dissection ( PLND ) is the gold st and ard for the detection of nodal disease . However , a new lymph-node-specific MR-contrast agent ferumoxtran-10 can detect metastases in normal-sized nodes ( ie , < 8 mm in size ) by use of MR lymphoangiography ( MRL ) . In this prospect i ve , multicentre cohort study , we aim ed to compare the diagnostic accuracy of MRL with up-to- date multidetector CT ( MDCT ) , and test the hypothesis that a negative MRL finding obviates the need for a PLND . METHODS We included consecutive patients with prostate cancer who had an intermediate or high risk ( risk of > 5 % according to routinely used nomograms ) of having lymph-node metastases . All patients were assessed by MDCT and MRL , and underwent PLND or fine-needle aspiration biopsy . Imaging results were correlated with histopathology . The primary outcomes were sensitivity , specificity , accuracy , NPV , and PPV of MRL and MDCT . This study is registered with Clinical Trials.gov , number NCT00185029 . FINDINGS The study was done in 11 hospitals in the Netherl and s between April 8 , 2003 , and April 19 , 2005 . 375 consecutive patients were included . 61 of 375 ( 16 % ) patients had lymph-node metastases . Sensitivity was 34 % ( 21 of 61 ; 95 % CI 23 - 48 ) for MDCT and 82 % ( 50 of 61 ; 70 - 90 ) for MRL ( McNemar 's test p<0.05 ) . Specificity was 97 % ( 303 of 314 ; 94 - 98 ) for MDCT and 93 % ( 291 of 314 ; 89 - 95 ) for MRL . Positive predictive value ( PPV ) was 66 % ( 21 of 32 ; 47 - 81 ) for MDCT and 69 % ( 50 of 73 ; 56 - 79 ) for MRL . Negative predictive value ( NPV ) was 88 % ( 303 of 343 ; 84 - 91 ) for MDCT and 96 % ( 291 of 302 ; 93 - 98 ) for MRL ( McNemar 's test p<0.05 ) . Of the 61 patients with lymph-node metastases , 50 were detected by MRL , of which 40 ( 80 % ) had metastases in normal-sized lymph nodes . The high sensitivity and NPV of MRL imply that in patients with a negative MRL , the chance of positive lymph nodes is less than 11/302 ( 4 % ) . INTERPRETATION MRL had significantly higher sensitivity and NPV than MDCT for patients with prostate cancer who had intermediate or high risk of having lymph-node metastases . In such patients , after a negative MRL , the post-test probability of having lymph-node metastases is low enough to omit a PLND OBJECTIVE In several previous studies , including one of our own , CT and MRI provided similar information on N2 detection in the staging of lung cancer . Both imaging techniques can be considered effective in detecting enlarged mediastinal lymph nodes but the results are often inaccurate when confronted with pathological findings . The purpose of this study was to assess the diagnostic accuracy of gadolinium-DTPA enhanced MRI in the detection of mediastinal lymph nodes in lung cancer . METHODS A prospect i ve study to compare st and ard unenhanced MRI and Gd-DTPA enhanced MRI was carried out in patients with diagnosed lung cancer . The study focused on the status of mediastinal lymph nodes . Gd-DTPA was administered at a dosage of 0.2 mmol2/KG before T1 weighted sequences . Qualitative visual analyses of both st and ard and contrast enhanced MRI images were performed on each patient by 2 independent radiologists . The imaging results were then compared to pathological findings obtained after surgical operation . RESULTS In the identification of mediastinal lymph node metastases st and ard MRI was 62 % sensitive , 100 % specific and 74 % accurate whereas Gd-DTPA enhanced MRI was 100 % sensitive , 91 % specific and 97 % accurate . CONCLUSIONS Gd-DPTA enhanced MRI was more accurate than st and ard MRI in the detection of metastatic lymph nodes in patients with lung cancer . These initial results can be considered encouraging especially with regards to the reduction of false negative findings although further confirmation is , underst and ably , required Abstract Background : We retrospectively evaluated the accuracy of magnetic resonance ( MR ) imaging in staging colorectal cancer and assessing local tumor extent , nodal involvement , and distant abdominal and pelvic metastases . Methods : Forty-eight patients with primary colorectal carcinoma were referred for presurgical abdominal and pelvic MR imaging . MR imaging included T1-weighted , fat-suppressed T2-weighted , and fat-suppressed gadolinium-enhanced spin gradient-echo imaging . The prospect i ve interpretations of the MR examinations were review ed . MR depiction of local tumor extent , nodal involvement , and distant metastases at 18 anatomic locations was noted and compared with subsequent surgical and histopathologic findings . Results : Overall TNM MR staging agreed with surgical and pathologic staging in 41 ( 85 % ) of 48 patients , including 21 ( 78 % ) of 27 colon cancers and 20 ( 95 % ) of 21 rectal cancers . For depth of tumor penetration , which was evaluable in 44 patients , MR imaging agreed with pathologic results in 38 ( 86 % ) of 44 patients , including 22 ( 88 % ) of 25 colon cancers and 16 ( 84 % ) of 19 rectal cancers . In 42 ( 95 % ) of 44 patients , MR images correctly distinguished tumor confined to the bowel wall ( T0 , T1 , and T2 ) from tumor with transmural tumor extension ( T3 and T4 ) . Regional nodal metastases were depicted in Output:	The overall accuracy of gadolinium-enhanced magnetic resonance imaging for the detection of nodal metastases is moderate . Incorporating contrast enhancement in the malignancy criteria substantially improves the accuracy of this diagnostic test
MS22587	*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 assess the effects of comprehensive cardiac rehabilitation compared with usual care on physical activity and mental health for patients treated with catheter ablation for atrial fibrillation . METHODS The patients were r and omized 1:1 stratified by paroxysmal or persistent atrial fibrillation and sex to cardiac rehabilitation consisting of 12 weeks physical exercise and four psycho-educational consultations plus usual care ( cardiac rehabilitation group ) versus usual care . The primary outcome was Vo2 peak . The secondary outcome was self-rated mental health measured by the Short Form-36 question naire . Exploratory outcomes were collected . RESULTS 210 patients were included ( mean age : 59 years , 74 % men ) , 72 % had paroxysmal atrial fibrillation prior to ablation . Compared with usual care , the cardiac rehabilitation group had a beneficial effect on Vo2 peak at four months ( 24.3mL kg-1 min-1 versus 20.7mL kg-1 min-1 , p of main effect=0.003 , p of interaction between time and intervention=0.020 ) . No significant difference between groups on Short Form-36 was found ( 53.8 versus 51.9 points , P=.20 ) . Two serious adverse events ( atrial fibrillation in relation to physical exercise and death unrelated to rehabilitation ) occurred in the cardiac rehabilitation group versus one in the usual care group ( death unrelated to intervention ) ( P=.56 ) . In the cardiac rehabilitation group 16 patients versus 7 in the usual care group reported non-serious adverse events ( P=.047 ) . CONCLUSION Comprehensive cardiac rehabilitation had a positive effect on physical capacity compared with usual care , but not on mental health . Cardiac rehabilitation caused more non-serious adverse events Background Natural history of paroxysmal atrial fibrillation ( AF ) is not very well documented . Clinical experience suggests that paroxysmal AF could progress to chronic AF with estimates ranging between 15 and 30 % over a period of 1–3 years . We performed an epidemiologic study to eluci date the natural history of paroxysmal AF , this study estimated its incidence in a general practice setting , identified associated factors and analyzed the progression into chronic AF as well as the mortality rate . Methods Using the UK General Practice Research Data base ( GPRD ) , we identified patients aged 40–89 years with a first-recorded episode of paroxysmal AF during 1996 . Risk factors were assessed using 525 incident paroxysmal AF cases confirmed by the general practitioner ( GP ) and a r and om sample of controls . We follow-up paroxysmal AF patients and estimated their mortality rate and progression to chronic AF . Results The incidence of paroxysmal AF was 1.0 per 1,000 person-years . Major risk factors for paroxysmal AF were age and prior valvular heart disease , ischaemic heart disease , heart failure and hyperthyroidism . During a mean follow-up of 2.7 years , 70 of 418 paroxysmal AF patients with complete information progressed to chronic AF . Risk factors associated with progression were valvular heart disease ( OR 2.7 , 95 % CI 1.2–6.0 ) and moderate to high alcohol consumption ( OR 3.0 , 95 % CI 1.1–8.0 ) . Paroxysmal AF patients did not carry an increased risk of mortality , compared to an age and sex matched sample of the general population . There was a suggestion of a small increased risk among patients progressing to chronic AF ( RR 1.5 , 96 % CI 0.8–2.9 ) . Conclusion Paroxysmal AF is a common arrhythmia in the general practice setting , increasing with age and commonly associated with other heart diseases . It sometimes is the initial presentation and then progress to chronic AF . A history of valvular heart disease and alcohol consumption are associated with this progression Aims This prospect i ve pilot- study was performed to assess whether regular moderate physical activity elevates the parasympathetic tone to the atrio-ventricular node and decreases VR during permanent AF . Background Adequate ventricular rate ( VR ) control in patients with permanent atrial fibrillation ( AF ) is not easy to accomplish . Methods 10 patients ( mean age 59 ± 10 years ) with permanent AF ( duration : 10 ± 8 years ) underwent moderate physical exercise adjusted to their individual physical capability ( 45 min walking/jogging twice a week ) . To analyze VR control physical exercise tests and Holter-ECG recordings were performed before and after 4 months . In addition , stepwise lactate tests and psycho-pathometric examinations were obtained . Results After 4 months of training , there was a trend toward a decrease of mean VR in 24 h Holter-ECGs by 12 % from 76 ± 20 to 67 ± 12 bpm ( P = 0.05 ) while there was no significant decrease of the minimal VR ( 38 ± 8 vs. 36.3 ± 4.5 bpm , P = 0.54 ) . At a lactate threshold of 2 mmol/l there was a trend towards an increase of the running speed from 105 ± 11 to 116 ± 12 m/min ( P = 0.05 ) . A significant VR decrease of 8 % ( range 5–10 % ) was observed at almost all exercise levels during exercise treadmill testing . Increases of exercise capacity and decreases of VR were accompanied by subjective improvements of health perception . Conclusion Regular moderate physical activity decreases VR at rest and during exercise while increasing exercise capacity . Physical training should be taken into account for ventricular rate control during AF AIMS The management of patients with atrial fibrillation ( AF ) is often inadequate due to deficient adherence to the guidelines . A nurse-led AF clinic providing integrated chronic care to improve guideline adherence and activate patients in their role , may effectively reduce morbidity and mortality but such care has not been tested in a large r and omized trial . Therefore , we performed a r and omized clinical trial to compare the AF clinic with routine clinical care in patients with AF . METHODS AND RESULTS We r and omly assigned 712 patients with AF to nurse-led care and usual care . Nurse-led care consisted of guidelines based , software supported integrated chronic care supervised by a cardiologist . The primary endpoint was a composite of cardiovascular hospitalization and cardiovascular death . Duration of follow-up was at least 12 months . Adherence to guideline recommendations was significantly better in the nurse-led care group . After a mean of 22 months , the primary endpoint occurred in 14.3 % of 356 patients of the nurse-led care group compared with 20.8 % of 356 patients receiving usual care [ hazard ratio : 0.65 ; 95 % confidence interval ( CI ) 0.45 - 0.93 ; P= 0.017 ] . Cardiovascular death occurred in 1.1 % in the nurse-led care vs. 3.9 % in the usual care group ( hazard ratio : 0.28 ; 95 % CI : 0.09 - 0.85 ; P= 0.025 ) . Cardiovascular hospitalization amounted ( 13.5 vs. 19.1 % , respectively , hazard ratio : 0.66 ; 95 % CI : 0.46 - 0.96 , P= 0.029 ) . CONCLUSION Nurse-led care of patients with AF is superior to usual care provided by a cardiologist in terms of cardiovascular hospitalizations and cardiovascular mortality . Trial registration information : Clinical trials.gov identifier number : NCT00391872 PURPOSE A r and omized study was conducted to determine whether short-term exercise training in patients with chronic atrial fibrillation ( AF ) might improve exercise capacity and quality of life ( QOL ) , and influence atrioventricular conduction . METHODS Atrial fibrillation patients ( age 64 + /- 7 years ) were r and omized to exercise training ( n = 15 ) or a 2-month control period ( n = 15 ) followed by the training program . Twenty-four training sessions consisted of aerobic exercise and muscle strengthening . A cycle ergometer test and a 15-minute resting high-frequency spectral electrocardiogram analysis were performed and a QOL question naire ( SF-36 ) was completed before and after training . Because there were no changes after 2 months in the control group , pooled data for all patients are presented before and after training . RESULTS Cumulated work at Borg scale 17 increased by 41 % + /- 36 % . Heart rate at rest and after 10 minutes of exercise decreased from 75 + /- 14 to 68 + /- 14 bpm and 145 + /- 19 to 137 + /- 21 bpm , respectively . HF increased from 81 + /- 17 to 91 + /- 22 milliseconds . Four of the 8 scales and 1 of the 2 summary scales of the Short-Form-36 improved . P < .05 for all results . CONCLUSIONS Exercise capacity , heart rate variability , and QOL improved after 2 months of exercise training in patients with chronic AF . Heart rates at rest and during exercise decreased Background Surprisingly little information on symptoms of paroxysmal atrial fibrillation is available in scientific literature . Using question naires , we have analyzed the symptoms associated with arrhythmia attacks . Methods One hundred r and omly-selected patients with idiopathic paroxysmal atrial fibrillation filled in a structured question naire . Results Psychic stress was the most common factor triggering arrhythmia ( 54 % ) , followed by physical exertion ( 42 % ) , tiredness ( 41 % ) coffee ( 25 % ) and infections ( 22 % ) . Thirty-four patients cited alcohol , 26 in the form of red wine , 16 as white wine and 26 as spirits . Among these 34 , red wine and spirits produced significantly more episodes of arrhythmia than white wine ( p = 0.01 and 0.005 respectively).Symptoms during arrhythmia were palpitations while exerting ( 88 % ) , reduced physical ability ( 87 % ) , palpitations at rest ( 86 % ) , shortage of breath during exertion ( 70 % ) and anxiety ( 59 % ) . Significant differences between sexes were noted regarding swollen legs ( women 21 % , men 6 % , p = 0.027 ) , nausea ( women 36 % , men 13 % , p = 0.012 ) and anxiety ( females 79 % , males 51 % , p = 0.014 ) . Conclusion Psychic stress was the commonest triggering factor in hospitalized patients with paroxysmal atrial fibrillation . Red wine and spirits were more proarrhythmic than white wine . Symptoms in women in connection with attacks of arrhythmia vary somewhat from those in men Background — Exercise training is an effective treatment for important atrial fibrillation ( AF ) comorbidities . However , a high level of endurance exercise is associated with an increased AF prevalence . We assessed the effects of aerobic interval training ( AIT ) on time in AF , AF symptoms , cardiovascular health , and quality of life in AF patients . Methods and Results — Fifty-one patients with nonpermanent AF were r and omized to AIT ( n=26 ) consisting of four 4-minute intervals at 85 % to 95 % of peak heart rate 3 times a week for 12 weeks or to a control group ( n=25 ) continuing their regular exercise habits . An implanted loop recorder measured time in AF continuously from 4 weeks before to 4 weeks after the intervention period . Cardiac function , peak oxygen uptake ( O2peak ) , lipid status , quality of life , and AF symptoms were evaluated before and after the 12-week intervention period . Mean time in AF increased from 10.4 % to 14.6 % in the control group and was reduced from 8.1 % to 4.8 % in the exercise group ( P=0.001 between groups ) . AF symptom frequency ( P=0.006 ) and AF symptom severity ( P=0.009 ) were reduced after AIT . AIT improved O2peak , left atrial and ventricular ejection fraction , quality -of-life measures of general health and vitality , and lipid values compared with the control group . There was a trend toward fewer cardioversions and hospital admissions after AIT . Conclusions — AIT for 12 weeks reduces the time in AF in patients with nonpermanent AF . This is followed by a significant improvement in AF symptoms , O2peak , left atrial and ventricular function , lipid levels , and QoL. Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01325675 BACKGROUND A r and omised study was conducted to determine if short-term exercise training in patients with chronic atrial fibrillation ( AF ) might improve symptoms and health-related quality of life ( HRQoL ) . METHODS AF patients ( 64+/-7 years ) were r and omised to exercise training ( n=15 ) or a 2-month control period ( n=15 ) followed by an exercise training program ( ETP ) . The ETP consisted of 24 training sessions with aerobic exercise and muscle strengthening . A cycle ergometer test , with recording of perceived exertion on the Borg scale , was performed . The participants completed HRQoL question naires , the Short-Form 36 ( SF-36 ) and Symptom and Severity Checklist ( SSCL ) , before and after training . Because there were no changes after two months in Output:	Due to few r and omised patients and outcomes , we could not evaluate the real impact of exercise-based cardiac rehabilitation on mortality or serious adverse events . The evidence showed no clinical ly relevant effect on health-related quality of life . Pooled data showed a positive effect on the surrogate outcome of physical exercise capacity , but due to the low number of patients and the moderate to very low- quality of the underpinning evidence , we could not be certain of the magnitude of the effect .
MS22588	*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 Minimally invasive , laparoscopically assisted surgery was first considered in 1990 for patients undergoing colectomy for cancer . Concern that this approach would compromise survival by failing to achieve a proper oncologic resection or adequate staging or by altering patterns of recurrence ( based on frequent reports of tumor recurrences within surgical wounds ) prompted a controlled trial evaluation . METHODS We conducted a noninferiority trial at 48 institutions and r and omly assigned 872 patients with adenocarcinoma of the colon to undergo open or laparoscopically assisted colectomy performed by credentialed surgeons . The median follow-up was 4.4 years . The primary end point was the time to tumor recurrence . RESULTS At three years , the rates of recurrence were similar in the two groups--16 percent among patients in the group that underwent laparoscopically assisted surgery and 18 percent among patients in the open-colectomy group ( two-sided P=0.32 ; hazard ratio for recurrence , 0.86 ; 95 percent confidence interval , 0.63 to 1.17 ) . Recurrence rates in surgical wounds were less than 1 percent in both groups ( P=0.50 ) . The overall survival rate at three years was also very similar in the two groups ( 86 percent in the laparoscopic-surgery group and 85 percent in the open-colectomy group ; P=0.51 ; hazard ratio for death in the laparoscopic-surgery group , 0.91 ; 95 percent confidence interval , 0.68 to 1.21 ) , with no significant difference between groups in the time to recurrence or overall survival for patients with any stage of cancer . Perioperative recovery was faster in the laparoscopic-surgery group than in the open-colectomy group , as reflected by a shorter median hospital stay ( five days vs. six days , P<0.001 ) and briefer use of parenteral narcotics ( three days vs. four days , P<0.001 ) and oral analgesics ( one day vs. two days , P=0.02 ) . The rates of intraoperative complications , 30-day postoperative mortality , complications at discharge and 60 days , hospital readmission , and reoperation were very similar between groups . CONCLUSIONS In this multi-institutional study , the rates of recurrent cancer were similar after laparoscopically assisted colectomy and open colectomy , suggesting that the laparoscopic approach is an acceptable alternative to open surgery for colon cancer PURPOSE Despite the major improvements that have been made due to total mesorectal excision ( TME ) , low rectal cancer still remains a challenge . METHODS By investigating a prospect i ve r and omized rectal cancer trial in which surgeons had undergone training in TME the factors responsible for the poor outcome were determined and a new method for assessing the quality of surgery was tested . RESULTS Survival differed greatly between abdominoperineal resection ( APR ) and anterior resection ( AR ; 38.5 % v 57.6 % , P = .008 ) . Low rectal carcinomas have a higher frequency of circumferential margin involvement ( 26.5 % v 12.6 % , P < .001 ) . More positive margins were present in the patients operated with APR ( 30.4 % ) compared to AR ( 10.7 % , P = .002 ) . Furthermore , more perforations were present in these specimens ( 13.7 % v 2.5 % , P < .001 ) . The plane of resection lies within the sphincteric muscle , the submucosa or lumen in more than 1/3 of the APR cases , and in the remainder lay on the sphincteric muscles . CONCLUSION We systematic ally described and investigated the pathologic properties of low rectal cancer in general , and APR in particular , in a prospect i ve r and omized trial including surgeons who had been trained in TME . The poor prognosis of the patients with an APR is ascribed to the resection plane of the operation leading to a high frequency of margin involvement by tumor and perforation with this current surgical technique . The clinical results of this operation could be greatly improved by adopting different surgical techniques and possibly greater use of radiochemotherapy Purpose Local recurrences are more common after abdominoperineal excision ( APE ) than after anterior resection of rectal cancer . Extralevator APE was introduced to address this problem . This prospect i ve registry-based population study aims to investigate the efficacy of extralevator APE ( ELAPE ) in improving short-term oncological outcome . Methods All Swedish patients operated with any kind of abdominoperineal excision and registered in the Swedish Rectal Cancer Registry 2007–2009 were included ( n = 1,397 ) and analyzed with emphasis on the perineal part of the operation . Short-term perioperative and oncological results were collected from the registry . Results Extralevator APE did not result in fewer intraoperative perforations or involved circumferential resection margins as compared to st and ard APE for the entire group . Intraoperative perforations were significantly fewer for patients with low tumours ( ≤4 cm ) ( ELAPE : n = 28/386 versus APE : n = 9/58 ) ( p = 0.043 ) and for early ( T0–T2 ) T-stages ( ELAPE : n = 3/172 versus APE : n = 6/75 ) ( p = 0.025 ) . There were significantly more post-operative wound infections for ELAPE than for APE ( n = 106 ( 20.4 % ) versus n = 25 ( 12.0 % ) , p = 0.011 ) . Conclusions The short-term results indicate that selective use of extralevator APE can be warranted , for example , for subgroups with low tumours . In conclusion , selective use of the extralevator APE is advocated as not all patients seem to benefit from the technique , and there are significantly more short-term complications after extralevator APE Purpose This study was to ascertain whether a robot-assisted ( RA ) approach to APR might facilitate a cylindrical APR by enabling a deeper pelvic dissection during an abdominal approach , concurrently comparing the feasibility and short-term oncologic outcomes . Methods Forty-eight consecutive patients with lower rectal cancer who had undergone curative APR ( 21 RA vs. 27 open ) were prospect ively enrolled . The short-term operative outcomes and oncologic feasibility were evaluated and compared . A levator muscle excision was performed concomitantly with the abdominal procedure in the RA group and with the perineal procedure in the open group . Results No patients in the RA group experienced intraoperative perforation or required conversion to open APR . Overall , a cylindrical APR was performed in 72 % of patients , and subtotal excision of the levator muscle , i.e. , either one or both sides of the puborectalis and pubococcygeus muscles , was more likely in the RA group ( P = 0.019 ) . A positive CRM was exclusively identified in four open APR patients . The mean number of retrieved lymph nodes was greater in the RA group ( 20 vs. 16 , P = 0.035 ) . There was no difference in perineal morbidity between the two groups ( P = 0.445 ) . Conclusions The RA approach facilitates an efficient excision in the pelvic region than open APR during the abdominal procedure . The RA approach also demonstrated a trend toward improved oncologic outcomes with equivalent postoperative morbidities than with the open approach BACKGROUND : Extralevator abdominoperineal excision for distal rectal cancers involves cylindrical excision of the mesorectum with wide division of the levator ani muscles . Although this technique has been shown to decrease local cancer recurrence and improve survival , it leaves the patient with a considerable pelvic floor defect that may require reconstruction . OBJECTIVE : We developed an innovative technique of robotic extralevator abdominoperineal excision combined with robotic harvest of the rectus abdominis muscle flap for immediate reconstruction of the pelvic floor defect . DESIGN : This was a retrospective review pilot study . SETTING : This study was conducted at a tertiary care cancer center . PATIENTS : Three patients who underwent robotic extralevator abdominoperineal excision with robotic rectus abdominis flap harvest for distal rectal adenocarcinoma were included . MAIN OUTCOMES MEASURES : Intraoperative and postoperative outcomes included operative time , intraoperative complications , length of hospital stay , wound complications , incidence of perineal hernia , persistent pain , and functional limitations . RESULTS : Three patients underwent this procedure . The median operative time was 522 minutes with median hospital stay of 6 days . One patient experienced perineal wound complication requiring limited incision and drainage followed by complete healing of the wound by secondary intention . The other 2 patients did not experience any wound complications . Longest follow-up was 16 months . None of the patients developed perineal hernias during this time period . LIMITATIONS : The small sample size and retrospective nature were limitations . CONCLUSIONS : This technique confers multiple advantages including improved visualization and dexterity within the pelvis and accurate wide margins at the pelvic floor . An incisionless robotic flap harvest with preservation of the anterior rectus sheath obviates the risk of ventral hernia while providing robust tissue closure of the radiated abdominoperineal excision wound . This technique may result in faster postoperative recovery , decreased morbidity , improved functional outcomes and cosmesis . Further studies are needed to prospect ively analyze this approach ( Supplemental Digital Content 1 , video abstract , http://links.lww.com/DCR/A188 ) BACKGROUND : Recent studies have shown that extralevator abdominoperineal resection has the potential for reduced circumferential resection margin involvement , intraoperative bowl perforation , and local recurrence rates ; however , it has been suggested that extended resection may be associated with increased morbidity because of the formation of a larger perineal defect . OBJECTIVE : This study was undertaken to demonstrate the feasibility and complications of extralevator abdominoperineal resection for locally advanced low rectal cancer in China . DESIGN : This was a prospect i ve cohort study . SETTING : The study was conducted at 7 university hospitals throughout China . PATIENTS : A total of 102 patients underwent this procedure for primary locally advanced low rectal cancer between August 2008 and October 2011 . MAIN OUTCOME MEASURES : The main outcome measures comprised circumferential resection margin involvement , intraoperative perforation , postoperative complications , and local recurrence . RESULTS : The most common complications included sexual dysfunction ( 40.5 % ) , perineal complications ( 23.5 % ) , urinary retention ( 18.6 % ) , and chronic perineal pain ( 13.7 % ) . Chronic perineal pain was associated with coccygectomy ( p < 0.001 ) , and the pain gradually eased over time . Reconstruction of the pelvic floor with biological mesh was associated with a lower rate of perineal dehiscence ( p = 0.006 ) and overall perineal wound complications ( p = 0.02 ) in comparison with primary closure . A positive circumferential margin was demonstrated in 6 ( 5.9 % ) patients , and intraoperative perforations occurred in 4 ( 3.9 % ) patients . All circumferential margin involvements and intraoperative perforations were located anteriorly . The local recurrence was 4.9 % at a median follow-up of 44 months ( range , 18–68 months ) . LIMITATIONS : This was a nonr and omized , uncontrolled study . CONCLUSIONS : Extralevator abdominoperineal resection performed in the prone position for low rectal cancer is a relatively safe approach with acceptable circumferential resection margin involvement , intraoperative perforations , and local recurrences . Reconstruction of the pelvic floor with biological mesh might lower the rate of perineal wound complications ( see Video , Supplemental Digital Content 1 , http://links.lww.com/DCR/A161 ) Output:	Conclusions Transabdominal division of the levators during APER is feasible and reproducible , with acceptable perioperative and good early oncological outcomes .
MS22589	*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 moderately elevated plasma total homocysteine ( tHcy ) , whether measured during fasting or post-methionine load ( PML ) , is increasingly being recognized as a risk factor for coronary artery diseases ( CAD ) . However , etiologies for moderately elevated plasma tHcy , particularly with regard to the role of genetic influence on plasma tHcy levels , are still not well understood . In the current investigation , we studied 1025 individuals with respect to the effect of the 68-bp insertion ( 844ins68 variant ) of the cystathionine beta-synthase ( CBS ) gene , the A(2756)G transition of the B(12)-dependent methionine synthase ( MS ) gene and the C(677)T transition of the methylenetetrahydrofolate reductase ( MTHFR ) gene on fasting and 4 h PML tHcy . Of these individuals , 153 ( 14.9 % ) were heterozygous for the 68-bp insertion , 329 ( 32.1 % ) were heterozygous for the G(2756 ) allele and 122 ( 11.9 % ) were homozygous for the C(677)T transition . Individuals heterozygous for the insertion had significantly lower PML increase in tHcy concentrations , while individuals homozygous for the A(2756)G transition had significantly lower fasting tHcy levels . A 2-way ANOVA showed that there was no interaction between the 844ins68 and the A(2756)G transition for either fasting tHcy or PML increase in tHcy , confirming the fact that the effect of these two genotypes on plasma tHcy levels are additive . The effects are opposite but additive with the C(677)50 % of all individuals in this study carried polymorphic traits , which predisposed them to either higher or lower plasma tHcy concentrations , thus providing new evidence of the importance of genetic influences as determinants of tHcy levels Background : Determinants of one-carbon metabolism , such as folate and vitamin B12 , have been implicated in cancer development . Previous studies have not provided conclusive evidence for the importance of circulating concentrations of folate and vitamin B12 in prostate cancer etiology . The aim of the present study was to investigate the relationship between prostate cancer risk and circulating concentrations of folate and vitamin B12 in a large prospect i ve cohort . Methods : We analyzed circulating concentrations of folate and vitamin B12 in 869 cases and 1,174 controls , individually matched on center , age , and date of recruitment , nested within the European Prospect i ve Investigation into Cancer and Nutrition cohort . Relative risks ( RR ) for prostate cancer were estimated using conditional logistic regression models . Results : Overall , no significant associations were observed for circulating concentrations of folate ( Ptrend = 0.62 ) or vitamin B12 ( Ptrend = 0.21 ) with prostate cancer risk . RRs for a doubling in folate and vitamin B12 concentrations were 1.03 [ 95 % confidence interval ( 95 % CI ) , 0.92 - 1.16 ] and 1.12 ( 95 % CI , 0.94 - 1.35 ) , respectively . In the subgroup of cases diagnosed with advanced stage prostate cancer , elevated concentrations of vitamin B12 were associated with increased risk ( RR for a doubling in concentration , 1.69 ; 95 % CI , 1.05 - 2.72 , Ptrend = 0.03 ) . No other subgroup analyses result ed in a statistically significant association . Conclusion : This study does not provide strong support for an association between prostate cancer risk and circulating concentrations of folate or vitamin B12 . Elevated concentrations of vitamin B12 may be associated with an increased risk for advanced stage prostate cancer , but this association requires examination in other large prospect i ve studies . ( Cancer Epidemiol Biomarkers Prev 2007;17(2):279–85 Methionine synthase ( MS ) encodes an enzyme that catalyzes the remethylation of homocysteine to methionine using a methyl group donated by 5-methyltetrahydrofolate , which is the major circulating form of folate in the body . Functional genetic variants of the MS may alter total homocysteine ( tHcy ) as well as folate levels which are independent risk factors for vascular disease . The influence of a common genetic polymorphism ( 2756A-->G , D919 G ) of the MS gene on plasma tHcy and folate levels and its relation to the risk of myocardial infa rct ion ( MI ) in a prospect i ve study of male physicians in the US was investigated . A nested case-control study was conducted within the Physicians ' Health Study which was originally design ed as a double-blind trial of aspirin and beta-carotene among 22071 US male physicians , aged 40 - 84 years in 1982 . Sixty-eight percent of participants also donated a blood sample . The study included 387 incident MI case and 767 controls matched on age , smoking status , and time from r and omization in 6-month intervals . Individuals with GG genotype had a non-significant reduction of MI risk ( RR 0.51 , 95 % CI 0.17 - 1.16 ) compared to individuals with DD genotype after adjusting for MI risk factors . The MS polymorphism was associated with decreased tHcy ( 10.55 , 9.87 and 9.57 nmol/ml for DD , DG and GG genotypes , respectively ) and increased folate levels ( 3.95 , 3.78 , 7.31 ng/ml for DD , DG and GG genotypes , respectively ) only among controls but not cases . It was concluded that influence of the MS ( D919 G ) polymorphism on the plasma tHcy and folate levels is at most moderate , but should be further investigated in other large prospect i ve studies It has been proposed that folate and polymorphisms of the enzyme methylenetetrahydrofolate reductase ( MTHFR ) , which regulates influx of folate from DNA synthesis and repair to methylation reactions , are involved in the aetiology of cancer . To relate the MTHFR 677C→T and 1298A→C polymorphisms to the risk of prostate cancer , taking into consideration prospect i ve plasma levels of folate , vitamin B12 and homocysteine . The design was a case – control study of 223 prostate cancer cases and 435 matched controls nested within the population -based Northern Sweden Health and Disease Cohort . Neither the MTHFR 677C→T nor the MTHFR 1298A→C polymorphism was statistically significantly associated with the risk of prostate cancer in univariate analysis by conditional logistic regression . After adjustment for MTHFR 1298A→C , plasma folate , vitamin B12 , homocysteine , body mass index and smoking , the odds ratios were , for the 677 CT genotype , 1.52 [ 95 % confidence interval ( CI ) 1.02–2.26 ] , and for TT , 0.91 ( 95 % CI 0.41–2.04 ) . Our previously reported observation of a possible increase in the risk of prostate cancer at high plasma folate levels was attributable in this study to subjects having the MTHFR 677C→T polymorphism . We found that the MTHFR 677C→T polymorphism is not likely to have a major role in the development of prostate cancer , although it may possibly increase the risk in combination with high plasma folate levels . Further investigation in larger studies is warranted The role of folate metabolism in cancer development is a topic of much current interest , with maintenance of adequate folate status tending to show a protective effect . Aberrant methylation , primarily hypermethylation of certain genes including tumor suppressors , has been implicated in prostate cancer development . Folate , vitamin B12 and homocysteine are essential for methyl group metabolism and thus also for DNA methylation . We related plasma levels of these factors to prostate cancer risk in a prospect i ve study of 254 case subjects and 514 matched control subjects . Increasing plasma levels of folate and vitamin B12 were statistically significantly associated with increased prostate cancer risk , with an odds ratio of 1.60 ( 95 % CI = 1.03 - 2.49 ; p(trend ) = 0.02 ) for folate and 2.63 ( 95 % CI = 1.61 - 4.29 ; p(trend ) < 0.001 ) for vitamin B12 for highest vs. lowest quartile . Increasing plasma homocysteine levels were associated with a reduced risk of borderline significance ( OR = 0.67 ; 95 % CI = 0.43 - 1.04 ; p(trend ) = 0.08 ) . After adjustment for the other 2 plasma variables , body mass index and smoking , a statistically significant increased risk remained only for vitamin B12 ( OR = 2.96 ; 95 % CI = 1.58 - 5.55 ; p(trend ) = 0.001 ) . Adjusted OR for folate and homocysteine were 1.30 ( 95 % CI = 0.74 - 2.24 ; p(trend ) = 0.17 ) and 0.91 ( 95 % CI = 0.51 - 1.58 ; p(trend ) = 0.60 ) , respectively . Our results suggest that factors contributing to folate status are not protective against prostate cancer . On the contrary , vitamin B12 , associated with an up to 3-fold increase in risk , and possibly also folate , may even stimulate prostate cancer development . These findings are novel and should be explored further in future studies Suboptimal DNA repair capacity is a risk factor for cancer that may be modulated by dietary nutrient intake , and serine hydroxymethyltransferase ( SHMT ) participates in folate metabolism and synthesis of purines and pyrimidines needed for DNA repair . Therefore , we tested our hypothesis that genetic variants of the cytosolic SHMT ( SHMT1 ) gene are associated with lung cancer risk . In a hospital-based case-control study of 1032 non-Hispanic white lung cancer patients and 1145 matched cancer-free controls , we genotyped five common SHMT1 polymorphisms either in the promoter , exons , or 3'-untranslated regions . Although the genotype and allele frequency distribution of each SNP did not differ between cases and controls statistically significantly in the single-locus analysis , the rs638416 polymorphism in the promoter alone and the combined putative risk variant genotypes containing rs643333C , rs638416 G , rs1979277 T , rs3738 G , and rs1979276C were associated with altered risk . Those carrying the combined 3 + risk variant genotypes had an increased risk of lung cancer ( adjusted OR=1.65 , 95 % CI=1.05 - 2.57 , compared with those having 0 - 1 risk genotypes ; and OR=1.21 , 95 % CI=1.01 - 1.45 , compared with those having 0 - 2 risk genotypes ) . The risk was more pronounced among older individuals ( > 61 years ) or those having a low total folate intake or a high methionine intake . No evidence of interactions between the putative SHMT risk variant genotypes and the selected variables was found . These results suggest that SHMT1 variants may play a role in the etiology of lung cancer , and our findings need to be verified in larger prospect i ve studies Elevation in plasma homocysteine concentration has been associated with vascular disease and neural tube defects . Methionine synthase is a vitamin B(12)-dependent enzyme that catalyses the remethylation of homocysteine to methionine . Therefore , defects in this enzyme may result in elevated homocysteine levels . One relatively common polymorphism in the methionine synthase gene ( D919 G ) is an A to G transition at bp 2,756 , which converts an aspartic acid residue believed to be part of a helix involved in co-factor binding to a glycine . We have investigated the effect of this polymorphism on plasma homocysteine levels in a working male population ( n = 607 ) in which we previously described the relationship of the C677 T " thermolabile " methylenetetrahydrofolate reductase ( MTHFR ) polymorphism with homocysteine levels . We found that the methionine synthase D919 G polymorphism is significantly ( P = 0.03 ) associated with homocysteine concentration , and the DD genotype contributes to a moderate increase in homocysteine levels across the homocysteine distribution ( OR = 1.58 , DD genotype in the upper half of the homocysteine distribution , P = 0.006 ) . Unlike thermolabile MTHFR , the homocysteine-elevating effects of the methionine synthase polymorphism are independent of folate and B(12 ) levels ; however , the DD genotype has a larger homocysteine-elevating effect in individuals with low B(6 ) levels . This polymorphism may , therefore , make a moderate , but significant , contribution to clinical conditions that are associated with elevated homocysteine PURPOSE To test a community population for the hypothesis that carcinogenesis is related to blood folate levels . METHODS Prospect i ve analysis of cancer mortality data for a coh Output:	We found no effect of MTHFR 677C > T or any of the other alleles in dominant , recessive or additive models , or in comparing a/a versus A/A homozygous . Neither did we find any difference in effects on advanced or localized cancers . Our meta- analysis suggests that known common folate-pathway single nucleotide polymorphisms do not have significant effects on susceptibility to prostate cancer
MS22590	*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 Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size & NA ; The efficacy of ketorolac , a non‐steroidal anti‐inflammatory drug , in the management of moderate to severe pain in adults , has led us to conduct a trial of this analgesic in children following tonsillectomy . Children were r and omized to receive intramuscular ( i.m . ) ketorolac ( 1 mg/kg , EXP group , n = 45 ) or saline ( CTL group , n = 42 ) at the completion of surgery . Intravenous ( i.v . ) fentanyl ( 0.5 & mgr;g/kg/dose ) was administered in repeated doses postoperatively . Pain intensity was measured using both the Oucher and the Children 's Hospital of Eastern Ontario Pain Scale ( CHEOPS ) to allow for comparison between self‐report and behavioral measures of pain intensity . Severity of postoperative bleeding was measured using a 4‐point rating scale . The EXP group had a significant reduction in total fentanyl dose ( mean : 35.9 & mgr;g ) compared to the CTL group ( mean : 48.3 & mgr;g , t = −2.21 , P < 0.03 ) . There was a statistically significant decrease in pre‐fentanyl CHEOPS scores in the Post‐Anesthesia Care Unit ( PACU ) in the ketorolac group ( F ( 2,30 ) = 5.34 , P < 0.01 ) , but not in the saline group ( F ( 2.24 ) = 2.46 , P > 0.05 ) . In the first hour postoperatively , the CHEOPS demonstrated significant decreases in pain intensity scores in response to opioids , in both groups . In the PACU , children were unable to provide a self‐report of pain intensity potentially due to a variety of factors ( e.g. , emergence delirium , agitation , excitement , sedation , and /or pain ) . However , during the remainder of the postoperative stay , the photographic scale of the Oucher was a more valid measure of pain intensity than the CHEOPS . There were no differences between the 2 groups in the severity of postoperative bleeding . Children in the EXP group were discharged significantly earlier ( i.e. , 30 min , t = −2.22 , P < 0.03 ) . Our data demonstrate that i.m . administration of ketorolac , at the end of surgery , significantly reduces opioid requirements and shortens length of stay without any evidence of increased bleeding . In addition , our data suggest that the patient 's altered level of consciousness and attention span may diminish the utility of self‐report measures of pain intensity in the immediate postoperative period Prophylactic administration of analgesics before surgery can decrease the intraoperative anaesthetic requirement and decrease pain during the early postoperative period . In a doubleblind , placebocontrolled study involving 90 healthy ASA physical status I or II children undergoing bilateral myringotomy , we compared the postoperative analgesic effects of oral acetaminophen and ketorolac , when administered 30 min before induction of anaesthesia . Patients were r and omized to receive saline ( 0.1 ml · kg−1 ) , acetaminophen ( 10 mg · kg−1 ) or ketorolac ( 1 mg · kg−1 ) diluted in cherry syrup to a total volume of 5 ml . Anaesthesia was induced and maintained with halothane and nitrous oxide via a face mask . Postoperative pain was assessed by a blinded observer using an objective pain scale . The three study groups were similar with respect to demographic data , duration of anaesthesia and surgery , induction behaviour , oxygen saturation , incidence of postoperative emesis and , recovery times . The ketorolac group had lower postoperative pain scores and required less frequent analgesic therapy in the early postoperative period compared with the acetaminophen and placebo groups . In contrast , there were no differences in pain scores or analgesic requirements between the acetaminophen and the placebo groups . We conclude that the preoperative administration of oral ketorolac , but not acetaminophen , provided better postoperative pain control than placebo in children undergoing bilateral myringotomy . RésuméL’administration prophylactique d’analgésiques avant la chirurgie peut diminuer les besoins anesthésiques peropératoires et la douleur durant la période postopératoire immédiate . Quatrevingtdix enfants avec un état physique ASA I ou II devant subir une myringotomie bilatérale participent à cette étude à doubleinsu avec un groupe contrôleplacebo . Sont comparés les effets analgésiques postopératoires de l’acétaminophène et du kétoralac administrés par voie orale 30 minutes avant l’induction anesthésique . Les patients reçoivent au hasard soit de la solution saline ( 0.1 ml · kg−1 ) , soit de l’acétaminophène ( 10 mg · kg−1 ) , soit du kétoralac ( 1 mg · kg−1 ) . Chacune des préparations est diluée dans un sirop à saveur de cerise pour faire un total de 5 ml . L’induction et l’entretien de l’anesthésie se font avec de l’halothane et du protoxyde d’azote administrés par masque . Un observateur non informé du médicament donné au patient évalue la douleur postoperatoire à l’aide d’une échelle de douleur objective . Les variables démographiques , la durée de l’anesthésie et de la chirurgie , le comportement à l’induction , la saturation artérielle en oxygène , l’incidence des vomissements postopératoires et le temps d’éveil sont comparables entre les trois groupes . Les patients du groupe kétoralac ont un pointage de douleur postopératoire plus bas que ceux des groupes acétaminophène et placebo , et Us nécessitent moins souvent un supplément analgésique . D’autre part , il n’ya pas de différence entre les groupes acétaminophène et placebo pour la douleur et les besoins analgésiques postopératoires . En conclusion , le kétoralac , mais pas l’acétaminophène , administré par la bouche avant la chirurgie assure une meilleure analgésie postopératoire qu’un placebo chez les enfants subissant une myringotomie bilatérale We studied the analgesic efficacy of tramadol 2 mg kg(-1 ) for post-operative analgesia after day-case adenoidectomy in children aged 1 - 3 yr . Eighty children were allocated r and omly to receive tramadol 2 mg kg(-1 ) i.v . or placebo immediately after induction of anaesthesia . Anaesthesia was induced with alfentanil 10 microg kg(-1 ) and propofol 4 mg kg(-1 ) followed by mivacurium 0.2 mg kg(-1 ) for tracheal intubation . Anaesthesia was continued with sevoflurane in nitrous oxide and oxygen . All children were given ibuprofen rectally at approximately 10 mg kg(-1 ) before the start of surgery . Post-operative pain and recovery assessment s were performed by a nurse blinded to the analgesic treatment using the Aldrete recovery score , the pain/discomfort scale and measurement of recovery times . Rescue medication ( pethidine in increments of 5 mg i.v . ) was administered according to the pain scores . A post-operative question naire was used to evaluate the need for analgesia at home up to 24 h after operation . Rescue analgesic at home was rectal or oral ibuprofen 125 mg . Children in the tramadol group required fewer pethidine doses than those in the placebo group ( P = 0.014 ) . Forty-five per cent of children receiving tramadol did not require post-operative analgesia at all compared with 15 % of children receiving placebo ( P = 0.003 ) . Recovery times and the incidence of adverse effects were similar in the two groups in the recovery room and at home . The requirement for rectal ibuprofen at home did not differ between groups UNLABELLED In this r and omized , double-blinded , placebo-controlled , prospect i ve study , we evaluated the analgesic efficacy of dextromethorphan 0.5 mg/kg or 1.0 mg/kg p.o . 1 h before adenotonsillectomy in 57 children 6 - 12 yr of age . Anesthetic management was st and ardized . Morphine 0.075 mg/kg i.v . and acetaminophen 25 - 35 mg/kg p.r . were administered after anesthetic induction but before the start of surgery . A 4-point behavioral score ( 1 = asleep , 2 = awake and calm , 3 = awake and crying , 4 = thrashing ) was recorded on admission to and discharge from the postanesthesia care unit ( PACU ) . In the PACU , pain was assessed with Children 's Hospital of Eastern Ontario Pain Scale ( CHEOPS ) and recorded every 15 min until the patient was transferred to the day surgery unit ( DSU ) . In the DSU , patients rated their pain using a 10-cm baseline 0 - 10 visual analog pain scale ( VAS ) every 30 min until they were discharged home . A 24-h VAS was obtained by phone interview , and parental satisfaction was scored ( yes/no ) regarding their child 's postoperative analgesia . Morphine 0.025 mg/kg i.v . was administered to children with CHEOPS score > 6 , who verbalized pain , or who were crying in any consecutive 5-min observation periods in the PACU . Total morphine consumption was recorded . The study groups were comparable with respect to demographic variables . We were unable to detect any differences between study groups with respect to postoperative morphine consumption , CHEOPS , behavior scores , VAS , or parental satisfaction . IMPLICATION S Premedication with dextromethorphan 0.5 or 1.0 mg/kg p.o . does not improve postoperative analgesia in school-aged children who receive preemptive morphine 0.075 mg/kg i.v . and acetaminophen 25 - 35 mg/kg p.r . during nitrous oxide and desflurane anesthesia for adenotonsillectomy After umbilical hernia surgery , and wound infiltration with bupivacaine 0.5 % , 17 children were given ketorolac 0.5 mg.kg-1 , with 18 controls receiving only the wound infiltration . No child experienced severe pain , but moderate pain was noted in patients in both groups . Objective and subjective pain scores were not different statistically at any point up to the morning after surgery Administration of analgesics before surgery can decrease the intra-operative anesthetic requirement and pain during the early post-operative period ( pre-emptive analgesia ) . The objective of this study was to evaluate an intra-muscular preparation of ketoprofen as analgesic in mild to moderate pain in children . In a double-blind placebo-controlled study , 91 healthy ASA I or II children undergoing squint opthalmic surgery was undertaken in the Ophthalmic Services at King Abdel-Aziz University Hospital Riyadh . The postoperative analgesic effects of intra-muscular pethidine and ketoprofen , just after the induction of anesthesia were compared . Patients were r and omized to receive ketoprofen ( 1 mg W kg-1 ) , pethidine ( 1 mg W kg-1 ) or saline ( 0.1 ml W kg-1 ) . Anesthesia was induced and maintained with halothane and nitrous oxide via Output:	Placebo control groups can be used in paediatric analgesic studies to demonstrate internal sensitivity
MS22591	*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 study poses two questions : 1 ) is there an abnormality in isokinetic skeletal muscle strength and endurance in mild chronic obstructive pulmonary disease ( COPD ) ? and 2 ) what is the effect of a r and omized , controlled , 12 week hospital outpatient weight training programme in terms of skeletal muscle function and exercise tolerance ? Upper and lower limb isokinetic maximum and sustained muscle function were compared in 43 COPD patients ( age 49+/-11 yrs ) , mean forced expiratory volume in one second ( FEV1 ) 77+/-23 % pred and 52 healthy , sedentary subjects ( age 51 ( 10 ) yrs ) , mean FEV1 109+/-16 % pred . The 43 COPD patients were r and omly allocated into training ( n=26 ) and control ( n=17 ) groups . Isokinetic and isotonic muscle function , whole body endurance , maximal exercise capacity and lung function were measured . The COPD patients had reduced isokinetic muscle function ( with the exception of sustained upper limb strength ) as compared with healthy sedentary subjects . Muscle function improved after weight training in the COPD patients . Whole body endurance during treadmill walking also improved with no change in maximal oxygen consumption . A deficit in skeletal muscle function can be identified in patients with mild chronic obstructive pulmonary disease which can not be explained by factors such as hypoxaemia and malnutrition . Intervention with weight training is effective in countering this deficit which the authors conclude is probably due to muscle deconditioning Changes in health according to World Health Organization ’s International Classification of Functioning , Disability and Health ( ICF ) after four weeks of pulmonary rehabilitation ( PR ) were investigated . Gender differences in the response to PR , and the correlation between improvements in the two components of ICF ( Body functions and Activities and Participation ) were examined . Twenty-two men and 18 women with chronic obstructive pulmonary disease in Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) stage II-IV attended in-patient , multidisciplinary PR consisting of endurance training four to five times/week at 70 % of peak work rate ( WRpeak ) , resistance training three to four times/week at 72 % of 15 repetitions maximum , educational sessions and individual counselling . The results were compared to those of 20 Chronic Obstructive Pulmonary Disease ( COPD ) patients included after the same criteria and investigated while waiting for admission to PR . In the rehabilitation group , we found significant improvements in health related quality of life ( HRQoL ) ( -7 units , St. George ’s Respiratory Question naire ) , arm ( 6 % ) and leg ( 15 % ) maximal voluntary contraction , peak oxygen uptake ( 6 % ) , WRpeak ( 60 % ) and treadmill endurance time ( 93 % ) . At iso-WR , ventilation and dyspnoea were significantly lower , but inspiratory capacity remained unchanged . Improvements in HRQoL correlated with increases in peak ventilation , but not in muscle strength or exercise capacity . Men improved their six-minute walking distance significantly in contrast to women . Clinical ly important improvements in HRQoL were found in two out of three of the men , and one out of three of the women . Four weeks of intensive PR generated significant health effects comparable to longer lasting programmes . Changes in exercise capacity and muscle strength were not related to improvements in HRQoL. The gender differences in the response to PR deserve attention in future studies PURPOSE The primary goal of pulmonary rehabilitation ( PR ) is for patients to achieve and maintain their maximum level of independence and functioning in the community . Traditional PR uses a predominantly aerobic/endurance approach to rehabilitation with little or no inclusion of exercises to increase strength . Few studies have investigated the impact of resistance training on PR despite growing evidence supporting its efficacy to improve physical function ( functional fitness ) in both healthy individuals and those with chronic disease . The purpose of this study was to investigate the effect of single-set resistance training on strength and functional fitness outcomes in PR patients . METHODS Twenty PR patients , 60 to 81 years old , were r and omly assigned to an 8-week endurance-based PR program ( ET ) or an ET plus resistance training program ( RT ) . RESULTS Strength increased in RT ( P < .05 ) and decreased in ET for both upper and lower body . Functional fitness improved ( P < .05 ) in 5 of 7 tests for RT compared with 2 tests for ET . CONCLUSIONS Single set RT can elicit significant improvements in both strength and functional fitness , which is not obtained by traditional PR alone . Our results are comparable to other studies with similar outcomes using multiple-set RT protocol s. These findings may have important implication s for program design , application , and adherence in PR BACKGROUND PATIENTS : with chronic airflow obstruction are often limited by muscle fatigue and weakness . As exercise rehabilitation programmes have produced modest improvements at best a study was design ed to determine whether specific muscle training techniques are helpful . METHODS : Thirty four patients with chronic airflow limitation ( forced expiratory volume in one second ( FEV1 ) 38 % of predicted values ) were stratified for FEV1 to vital capacity ( VC ) ratio less than 40 % and arterial oxygen desaturation during exercise and r and omised to a control or weightlifting training group . In the experimental group training was prescribed for upper and lower limb muscles as a percentage of the maximum weight that could be lifted once only . It was carried out three times a week for eight weeks . RESULTS : Three subjects dropped out of each group ; results in the remaining 14 patients in each group were analysed . Adherence in the training group was 90 % . In the trained subjects muscle strength and endurance time during cycling at 80 % of maximum power output increased by 73 % from 518 ( SE69 ) to 898 ( 95 ) s , with control subjects showing no change ( 506 ( 86 ) s before training and 479 ( 89 ) s after training ) . No significant changes in maximum cycle ergometer exercise capacity or distance walked in six minutes were found in either group . Responses to a chronic respiratory question naire showed significant improvements in dyspnoea and mastery of daily living activities in the trained group . CONCLUSIONS : Weightlifting training may be successfully used in patients with chronic airflow limitation , with benefits in muscle strength , exercise endurance , and subjective responses to some of the dem and s of daily living This r and omized , controlled study investigated the physiological effects of a specially design ed 12 week programme of isolated conditioning of peripheral skeletal muscle groups . The programme required minimal infrastructure in order to allow continued rehabilitation at home after familiarization within hospital . Forty eight patients , aged 40 - 72 yrs with chronic obstructive pulmonary disease ( COPD ) ( mean ( SD ) forced expiratory volume in one second ( FEV1 ) 61 (27)% of predicted normal ) were r and omly allocated into training ( n = 32 ) and control ( n = 16 ) groups . Physiological assessment s were performed before and after the 12 week study period , and included peripheral muscle endurance and strength , whole body endurance , maximal exercise capacity ( maximum oxygen consumption ( V'O2,max ) ) and lung function . The training group showed significant improvement in a variety of measures of upper and lower peripheral muscle performance , with no additional breathlessness . Whole body endurance measured by free arm treadmill walking increased by 6,372 ( 3,932 - 8,812 ) 3 ( p < 0.001 ) . Symptom-limited maximal V'O2 was unchanged . However , the training group showed a reduction in ventilatory equivalents for oxygen and carbon dioxide , both at peak exercise and at equivalent work rate ( Wmax ) . In summary , low intensity isolated peripheral muscle conditioning is well-tolerated , simple and easy to perform at home . The various physiological benefits should enable patients across the range of severity of chronic obstructive pulmonary disease to improve daily functioning PURPOSE Pulmonary rehabilitation programs are effective in patients with severe chronic obstructive pulmonary disease ( COPD ) in the short term , but their long-term effects are not known . We investigated the short- and long-term effects of a 6-month outpatient rehabilitation program in patients with severe COPD . SUBJECTS AND METHODS One hundred patients were r and omly assigned to receive either an exercise training program that included cycling , walking , and strength training ( n = 50 ) or usual medical care ( n = 50 ) . Thirty-four patients in the training group were evaluated after 6 months ( end of training ) , and 26 were evaluated after 18 months of follow-up . In the control group , 28 patients were evaluated at 6 months and 23 after 18 months . We measured pulmonary function , 6-minute walking distance , maximal exercise capacity , peripheral and respiratory muscle strength , and quality of life ( on a 20 to 140-point scale ) , and estimated the cost-effectiveness of the program . RESULTS At 6 months , the training group showed improvement in 6-minute walking distance [ mean difference ( training - control ) of 52 m ; 95 % confidence interval ( CI ) , 15 to 89 m ] , maximal work load ( 12 W ; 95 % CI , 6 to 19 W ) , maximal oxygen uptake ( 0.26 liters/min ; 95 % CI , 0.07 to 0.45 liters/min ) , quadriceps force ( 18 Nm ; 95 % CI , 7 to 29 Nm ) , inspiratory muscle force ( 11 cm H(2)O ; 95 % CI , 3 to 20 cm H(2)O ) , and quality of life ( 14 points ; 95 % CI , 6 to 21 points ; all P < 0.05 ) . At 18 months all these differences persisted ( P < 0.05 ) , except for inspiratory muscle strength . For 6-minute walking distance and quality of life , the differences between the training group and controls at 18 months exceeded the minimal clinical ly-important difference . CONCLUSION Among patients who completed the 6-month program , outpatient training result ed in significant and clinical ly relevant changes in 6-minute walking distance , maximal exercise performance , peripheral and respiratory muscle strength , and quality of life . Most of these effects persisted 18 months after starting the program The effects of endurance training on exercise capacity and health-related quality of life ( HRQL ) in chronic obstructive pulmonary disease ( COPD ) patients have been studied thoroughly , while resistance training has been rarely evaluated . This study investigated the effects of resistance training in comparison with endurance training in patients with moderate to severe COPD and peripheral muscle weakness ( isometric knee extension peak torque < 75 % predicted ) . Forty-eight patients ( age 64±8 yrs , forced expiratory volume in one second 38±17 % pred ) were r and omly assigned to resistance training ( RT , n=24 ) or endurance training ( ET , n=24 ) . The former consisted of dynamic strengthening exercises . The latter consisted of walking , cycling and arm cranking . Respiratory and peripheral muscle force , exercise capacity , and HRQL were re-evaluated in all patients who completed the 12-week rehabilitation ( RT n=14 , ET n=16 ) . Statistically significant increases in knee extension peak torque ( RT 20±21 % , ET 42±21 % ) , maximal knee flexion force ( RT 31±39 % , ET 28±37 % ) , elbow flexion force ( RT 24±19 % , ET 33±25 % ) , 6-min walking distance ( 6MWD ) ( RT 79±74 m , ET 95±57 m ) , maximum workload ( RT 15±16 Watt , ET 14±13 Watt ) and HRQL ( RT 16±25 points , ET 16±15 points ) were observed . No significant differences in changes in HRQL and 6MWD were seen between the two treatments . Resistance training and endurance training have similar effects on peripheral muscle force , exercise capacity and health-related quality of life in chronic obstructive pulmonary disease patients with peripheral muscle weakness Dysfunction of the muscles of ambulation contributes to exercise intolerance in chronic obstructive pulmonary disease ( COPD ) . Men with COPD have high prevalence of low testosterone levels , which may contribute to muscle weakness . We determined effects of testosterone supplementation ( 100 mg of testosterone enanthate injected weekly ) with or without resistance training ( 45 minutes three times weekly ) on body composition and muscle function in 47 men with COPD ( mean FEV(1 ) = 40 % predicted ) and low testosterone levels ( mean = 320 ng/dl ) . Subjects were r and omized to 10 weeks of placebo injections + no training , testosterone injections + no training , placebo injections + resistance training , or testosterone injections + resistance training . Testosterone injections yielded a mean increase of 271 ng/dl in the nadir serum testosterone concentration ( to the middle of the normal range for young men ) . The lean body mass ( by dual-energy X-ray absorptiometry ) increase averaged 2.3 kg with testosterone alone and 3.3 kg with combined testosterone and resistance training ( p < 0.001 ) . Increase in one-repetition maximum leg press strength averaged 17.2 % with testosterone alone , 17.4 % with resistance training alone , and 26.8 % with testosterone + resistance training ( p < 0.001 ) . Interventions were well tolerated with no abnormal Output:	Conclusions Based on findings from the meta- analysis , RT produces a clinical ly and statistically significant effect on respiratory function ( such as forced vital capacity ) and is therefore recommended in the management of COPD
MS22592	*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: Until 1990 , the survival of children with acute lymphoblastic leukaemia ( ALL ) in Russia was below 10 % . To establish a protocol feasible under conditions there , ALL-MB 91 was design ed to avoid prolonged bone marrow aplasia , thereby reducing needs for extensive supportive care , blood transfusions , long-lasting hospitalization and costs . High-dose therapies were avoided , anthracycline use was limited and CNS radiation therapy only foreseen in high-risk patients ( about 30 % ) . This was r and omized against a modified BFM protocol . From 1995 to 2002 , 834 patients of age up to 18 years were registered in 10 centres and 713 received after central r and omization the allocated risk-stratified treatment . After a median follow-up of 7 years , the event-free survival ( EFS ) was 67±3 % on ALL-MB 91 ( N=358 ) vs 68±3 % on ALL-BFM 90 m ( N=355 ) . The overall survival ( OS ) was 71±3 % vs 74±2 % , respectively . Anaemia , thrombocytopenia , agranulocytosis > 10 days and hospitalization ( median 35 vs 68 days ) were lower on ALL-MB 91 ( P<0.01 , N=197 ) . While EFS and OS were similar with both protocol s , ALL-MB 91 significantly incurred fewer toxicity and re source requirements and , therefore , has been increasingly used across Russia In a series of 40 patients treated with L-asparaginase for various neoplastic diseases , 6 patients had generalized anaphylactic reactions to L-asparaginase . Each of these reactors had antibodies detectable by passive hemagglutination , but precipitins were detectable in only one of this group of six patients . That patient had received two courses of the enzyme . 1 wk after the anaphylactic reaction , complement-fixing antibodies were present in all the patients that were studied . Specific reagin antibodies ( IgE ) were demonstrated in one patient by the release of histamine from his leukocytes after incubation in vitro with L-asparaginase . Binding of L-asparaginase to serum antibodies after incubation in vitro was detected by selective precipitation of the complexes with 30 % ammonium sulfate or by ultracentrifugation . Total inactivation of the enzyme did not occur even at optimal proportions or at antibody excess . Passive hemagglutinating antibodies to L-asparaginase were present in all patients who had an allergic reaction at least 1 day before the reaction occurred , when that sample was available , and were absent in all patients who did not manifest clinical allergy . Titration of antibodies by passive hemagglutination may thus provide a means of predicting impending anaphylaxis in this system , particularly when coupled with a sudden decrease in circulating levels of L-asparaginase activity BACKGROUND l-asparaginase is a universal component of treatment for childhood acute lymphoblastic leukaemia , and is usually administered intramuscularly . Pegylated Escherichia coli asparaginase ( PEG-asparaginase ) has a longer half-life and is potentially less immunogenic than the native Escherichia coli ( E coli ) preparation , and can be more feasibly administered intravenously . The aim of the Dana-Farber Cancer Institute Acute Lymphoblastic Leukaemia Consortium Protocol 05 - 001 ( DFCI 05 - 001 ) was to compare the relative toxicity and efficacy of intravenous PEG-asparaginase and intramuscular native E colil-asparaginase in children with newly diagnosed acute lymphoblastic leukaemia . METHODS DFCI 05 - 001 enrolled patients aged 1 - 18 years with newly diagnosed acute lymphoblastic leukaemia from 11 consortium sites in the USA and Canada . Patients were assigned to an initial risk group on the basis of their baseline characteristics and then underwent 32 days of induction therapy . Those who achieved complete remission after induction therapy were assigned to a final risk group and were eligible to participate in a r and omised comparison of intravenous PEG-asparaginase ( 15 doses of 2500 IU/m(2 ) every 2 weeks ) or intramuscular native E colil-asparaginase ( 30 doses of 25 000 IU/m(2 ) weekly ) , beginning at week 7 after study entry . R and omisation ( 1:1 ) was unmasked , and was done by a statistician-generated allocation sequence using a permuted blocks algorithm ( block size of 4 ) , stratified by final risk group . The primary endpoint of the r and omised comparison was the overall frequency of asparaginase-related toxicities ( defined as allergy , pancreatitis , and thrombotic or bleeding complications ) . Predefined secondary endpoints were disease-free survival , serum asparaginase activity , and quality of life during therapy as assessed by PedsQL surveys . All analyses were done by intention to treat . This study is registered with Clinical Trials.gov , number NCT00400946 . FINDINGS Between April 22 , 2005 , and Feb 12 , 2010 , 551 eligible patients were enrolled . 526 patients achieved complete remission after induction , of whom 463 were r and omly assigned to receive intramuscular native E colil-asparaginase ( n=231 ) or intravenous PEG-asparaginase ( n=232 ) . The two treatment groups did not differ significantly in the overall frequency of asparaginase-related toxicities ( 65 [ 28 % ] of 232 patients in the intravenous PEG-asparaginase group vs 59 [ 26 % ] of 231 patients in the intramuscular native E colil-asparaginase group , p=0·60 ) , or in the individual frequency of allergy ( p=0·36 ) , pancreatitis ( p=0·55 ) , or thrombotic or bleeding complications ( p=0·26 ) . Median follow-up was 6·0 years ( IQR 5·0 - 7·1 ) . 5-year disease-free survival was 90 % ( 95 % CI 86 - 94 ) for patients assigned to intravenous PEG-asparaginase and 89 % ( 85 - 93 ) for those assigned to intramuscular native E colil-asparaginase ( p=0·58 ) . The median nadir serum asparaginase activity was significantly higher in patients who received intravenous PEG-asparaginase than in those who received intramuscular native E colil-asparaginase . Significantly more anxiety was reported by both patients and parent-proxy in the intramuscular native E colil-asparaginase group than in the intravenous PEG-asparaginase group . Scores for other domains were similar between the groups . The most common grade 3 or worse adverse events were bacterial or fungal infections ( 47 [ 20 % ] of 232 in the intravenous PEG-asparaginase group vs 51 [ 22 % ] of 231 patients in the intramuscular E colil-asparaginase group ) and asparaginase-related allergic reactions ( 14 [ 6 % ] vs 6 [ 3 % ] ) . INTERPRETATION Intravenous PEG-asparaginase was not more toxic than , was similarly efficacious to , and was associated with decreased anxiety compared with intramuscular native E colil-asparaginase , supporting its use as the front-line asparaginase preparation in children with newly diagnosed acute lymphoblastic leukaemia . FUNDING National Cancer Institute and Enzon Pharmaceuticals Much progress has been made in the biological characterization of acute lymphoblastic leukemia ( ALL ) . Many biologic features with prognostic significance have been used together with clinical factors to define patient groups for risk-adapted therapy . However , it is well recognized that the prognostic significance of virtually all variables depends on the type and intensity of treatment . The differences in risk classification , eligibility ( eg upper or lower age limit ) and composition of ethnic or racial population have made it difficult to compare results between study groups . The comparison is further complicated by the inclusion of only subsets of patients in some publications . In October 1985 , an international workshop ( organized by R Mastrangelo ) was held in Rome during which recommendations were made to report study results by common , easily available criteria ( age and presenting leukocyte count ) ; to collect prospect ively information on organ involvement , immunphenotype , genetics and treatment response ; and to use st and ard statistical methods to analyze data .4 Despite this effort , different risk classifications continue to be used , and a large number of clinical trials had been conducted on subgroups of ALL , especially in the USA . In 1993 , the US National Cancer Institute organized a workshop for the US cooperative study groups and major institutions to develop uniform risk criteria . The recommendations published in 19965 were more widely accepted . The major groups defined by age and leukocyte count were identical to that of the Rome workshop ( Table 1 ) . While the importance of cytogenetics and molecular genetics were recognized , they were not included in the risk criteria because the tests were not widely available at that time . BACKGROUND Minimal residual disease ( MRD ) is the most sensitive and specific predictor of relapse risk in children with acute lymphoblastic leukaemia ( ALL ) during remission . We assessed whether treatment intensity could be adjusted for children and young adults according to MRD risk stratification . METHODS Between Oct 1 , 2003 and June 30 , 2011 , consecutive children and young adults ( aged 1 - 25 years ) with ALL from the UK and Irel and were recruited . Eligible patients were categorised into clinical st and ard , intermediate , and high risk groups on the basis of a combination of National Cancer Institute ( NCI ) criteria , cytogenetics , and early response to induction therapy , which was assessed by bone marrow blast counts taken at days 8 ( NCI high-risk patients ) and 15 ( NCI st and ard-risk patients ) after induction began . Clinical st and ard-risk and intermediate-risk patients were assessed for MRD . Those classified as MRD low risk ( undetectable MRD at the end of induction [ day 29 ] or detectable MRD at day 29 that became undetectable by week 11 ) were r and omly assigned to receive one or two delayed intensification courses . Patients had received induction , consolidation , and interim maintenance therapy before they began delayed intensification . Delayed intensification consisted of pegylated asparaginase on day 4 ; vincristine , dexamethasone ( alternate weeks ) , and doxorubicin for 3 weeks ; and 4 weeks of cyclophosphamide and cytarabine . Computer r and omisation was done with stratification by MRD result and balancing for sex , age , and white blood cell count at diagnosis by method of minimisation . Patients , clinicians , and data analysts were not masked to treatment allocation . The primary outcome was event-free survival ( EFS ) , which was defined as time to relapse , secondary tumour , or death . Our aim was to rule out a 7 % reduction in EFS in the group given one delayed intensification course relative to that given two delayed intensification courses . Analyses were by intention to treat . This trial is registered , number IS RCT N07355119 . FINDINGS Of 3207 patients registered in the trial overall , 521 MRD low-risk patients were r and omly assigned to receive one ( n=260 ) or two ( n=261 ) delayed intensification courses . Median follow-up of these patients was 57 months ( IQR 42 - 72 ) . We recorded no significant difference in EFS between the group given one delayed intensification ( 94·4 % at 5 years , 95 % CI 91·1 - 97·7 ) and that given two delayed intensifications ( 95·5 % , 92·8 - 98·2 ; unadjusted odds ratio 1·00 , 95 % CI 0·43 - 2·31 ; two-sided p=0·99 ) . The difference in 5-year EFS between the two groups was 1·1 % ( 95 % CI -5·6 to 2·5 ) . 11 patients ( actuarial relapse at 5 years 5·6 % , 95 % CI 2·3 - 8·9 ) given one delayed intensification and six ( 2·4 % , 0·2 - 4·6 ) given two delayed intensifications relapsed ( p=0·23 ) . Three patients ( 1·2 % , 0 - 2·6 ) given two delayed intensifications died of treatment-related causes compared with none in the group given one delayed intensification ( p=0·08 ) . We recorded no significant difference between groups for serious adverse events and grade 3 or 4 toxic effects ; however , the second delayed intensification course was associated with one ( < 1 % ) treatment-related death , and 74 episodes of grade 3 or 4 toxic effects in 45 patients ( 17 % ) . INTERPRETATION Treatment reduction is feasible for children and young adults with ALL who are predicted to have a low risk of relapse on the basis of rapid clearance of MRD by the end of induction therapy . FUNDING Medical Research Council and Leukaemia and Lymphoma Research BACKGROUND To evaluate if dissolution of asparaginase in lidocaine can relieve pain of an intramuscular injection in children without changes in bioavailability . PROCEDURE The study was design ed as a double-blinded study , Output:	The fixed effects pooled odds ratio after adjusting for publication bias was 2.49 ( 95 % CI 1.62 - 3.83 ) , indicating a significantly higher risk of hypersensitivity for IV over IM PEG-ASP . Although administering PEG-ASP through IV is preferable for patients , it poses a significantly higher risk of hypersensitivity when compared with IM administration , especially for HR patients .
MS22593	*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 study poses two questions : 1 ) is there an abnormality in isokinetic skeletal muscle strength and endurance in mild chronic obstructive pulmonary disease ( COPD ) ? and 2 ) what is the effect of a r and omized , controlled , 12 week hospital outpatient weight training programme in terms of skeletal muscle function and exercise tolerance ? Upper and lower limb isokinetic maximum and sustained muscle function were compared in 43 COPD patients ( age 49+/-11 yrs ) , mean forced expiratory volume in one second ( FEV1 ) 77+/-23 % pred and 52 healthy , sedentary subjects ( age 51 ( 10 ) yrs ) , mean FEV1 109+/-16 % pred . The 43 COPD patients were r and omly allocated into training ( n=26 ) and control ( n=17 ) groups . Isokinetic and isotonic muscle function , whole body endurance , maximal exercise capacity and lung function were measured . The COPD patients had reduced isokinetic muscle function ( with the exception of sustained upper limb strength ) as compared with healthy sedentary subjects . Muscle function improved after weight training in the COPD patients . Whole body endurance during treadmill walking also improved with no change in maximal oxygen consumption . A deficit in skeletal muscle function can be identified in patients with mild chronic obstructive pulmonary disease which can not be explained by factors such as hypoxaemia and malnutrition . Intervention with weight training is effective in countering this deficit which the authors conclude is probably due to muscle deconditioning BACKGROUND AND OBJECTIVE Non-invasive ventilation ( NIV ) might improve peripheral muscle function and exercise capacity in severely disabled patients . This study evaluated the physiological impact of NIV on isokinetic concentric strength and endurance of lower limb muscles in patients with severe COPD . METHODS This clinical trial tested COPD patients ( n = 24 ) and healthy subjects ( n = 18 ) . Subjects underwent isokinetic dynamometry tests while given either bi-level positive airway pressure ventilation ( BV ) or sham ventilation ( SV ) , in a r and omized order with 30 min of rest prior to each intervention . The inspiratory level of BV was set up to 14 cm H(2)O and expiratory pressure up to 6 cm H(2)O. Peripheral oxygen saturation ( SpO(2 ) ) , heart rate ( HR ) , systolic ( SBP ) and diastolic blood pressure ( DBP ) at the peak of exercise were measured for each intervention . RESULTS Compared with controls , COPD patients had lower values of SpO(2 ) and HR ( P < 0.01 ) during both BV and SV and lower values of DBP ( P < 0.01 ) during BV . BV improved SpO(2 ) ( P < 0.01 ) , and reduced SBP in both COPD ( P < 0.01 ) and control groups ( P < 0.05 ) and reduced DBP in COPD patients ( P < 0.01 ) . BV also reduced the fatigue index in COPD patients when compared with SV ( P = 0.003 ) . Variation ( BV-SV ) of total work at the peak of the test was higher in the control group than in the COPD group ( P < 0.05 ) . CONCLUSIONS BV improved SpO(2 ) and reduced the fatigability of the quadriceps muscle in patients with severe COPD . These results support the need for further evaluation of BV as adjunct during high-intensity strength exercise training in these patients Improving reduced skeletal muscle function is important for optimising exercise tolerance and quality of life in chronic obstructive pulmonary disease ( COPD ) patients . By applying high-intensity training to a small muscle group , we hypothesised a normalisation of muscle function . Seven patients with COPD performed 6 weeks ( 3 days·week−1 ) of high-intensity interval aerobic knee extensor exercise training . Five age-matched healthy individuals served as a reference group . Muscle oxygen uptake and mitochondrial respiration of the vastus lateralis muscle were measured before and after the 6-week training programme . Initial peak work and maximal mitochondrial respiration were reduced in COPD patients and improved significantly after the training programme . Peak power and maximal mitochondrial respiration in vastus lateralis muscle increased to the level of the control subjects and were mainly mediated via improved complex I respiration . Furthermore , when normalised to citrate synthase activity , no difference in maximal respiration was found either after the intervention or compared to controls , suggesting normal functioning mitochondrial complexes . The present study shows that high-intensity training of a restricted muscle group is highly effective in restoring skeletal muscle function in COPD patients 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 Background Exacerbations of chronic obstructive pulmonary disease ( COPD ) are characterised by increased dyspnoea , reduced quality of life and muscle weakness . Re-exacerbation and hospital admission are common . Pulmonary rehabilitation ( PR ) administered after hospital admission for an exacerbation can improve quality of life and exercise capacity . Objective To determine whether outpatient post-exacerbation PR ( PEPR ) could reduce subsequent hospital admission episodes . Methods Patients admitted to hospital for an exacerbation of COPD were r and omised to receive either usual follow-up care ( UC ) or PEPR after discharge . Hospital admission and emergency department attendances for COPD exacerbations were recorded over a 3-month period and analysed on an intention-to-treat basis . Secondary outcomes included exercise capacity and quadriceps strength . Results 60 patients underwent concealed r and omisation at the time of their hospital discharge ( UC : n=30 , mean ( SD ) age 65 ( 10 ) years , forced expiratory volume in 1 s ( FEV1 ) 52 (22)% predicted ; PEPR : n=30 , 67(10 ) years , 52 (20)% predicted ) . The proportion of patients re-admitted to hospital with an exacerbation was 33 % in the UC group compared with 7 % in those receiving PEPR ( OR 0.15 , 95 % CI 0.03 to 0.72 , p=0.02 ) . The proportion of patients that experienced an exacerbation result ing in an unplanned hospital attendance ( either admission or review and discharge from the emergency department ) was 57 % in the UC group and 27 % in those receiving PEPR ( OR 0.28 , 95 % CI 0.10 to 0.82 , p=0.02 ) . Conclusions Post-exacerbation rehabilitation in COPD can reduce re-exacerbation events that require admission or hospital attendance over a 3-month period . Clinical Trials Registration Number NCT00557115 PURPOSE Lower-limb muscle weakness has often been reported in COPD , and contributes to exercise intolerance . Controversial information is available regarding upper-limb muscle adaptations and the influence of muscle wasting on muscle weakness . We investigated leg and arm muscle function in 59 stable COPD patients ( GOLD stage III ) with preserved fat-free mass ( FFM ) and in 28 patients with reduced FFM relative to age- and sex-matched healthy control subjects and studied the effects of 8 wk of whole-body exercise training . METHODS FFM was measured with bioelectrical impedance analysis . Isokinetic quadriceps ( F-leg ) and biceps strength ( F-arm ) , as well as quadriceps ( E-leg ) and biceps endurance ( E-arm ) were determined with a Biodex dynamometer . Exercise training consisted of cycle ergometry , treadmill walking , weight training , and gymnastics during 5 d.wk . RESULTS F-leg ( 76.2 + /- 3.6 vs 118.2 + /- 6.3 N.m , P < 0.001 ) and F-arm ( 25.6 + /- 1.3 vs 38.1 + /- 2.1 N.m , P < 0.001 ) were significantly and similarly reduced in the COPD patient group compared with controls . Also , E-leg ( -2.13 + /- 0.12 vs -1.61 + /- 0.11 , P < 0.01 ) , but not E-arm ( -2.72 + /- 0.11 and -2.47 + /- 0.13 NS ) , was decreased in patients . F-leg ( 62.4 + /- 4.3 vs 82.8 + /- 4.7 N.m , P < 0.01 ) , but not F-arm or muscle endurance , was reduced in FFM-depleted compared with non-FFM-depleted patients . Whereas after training F-leg and E-leg significantly increased by 20 % in the whole COPD group , biceps muscle function remained unchanged . CONCLUSION Lower- and upper-limb muscle dysfunction was observed in COPD patients , irrespective of the presence of FFM depletion . Generalized muscle weakness suggests systemic muscular involvement , although the preserved arm endurance and the poor response of arm performance to exercise training is indicative for intrinsic differences in muscular adaptations between leg and arm muscles BACKGROUND In addition to the respiratory limitation in patients with chronic obstructive pulmonary disease ( COPD ) , skeletal muscle abnormalities may occur and contribute to the exercise intolerance . This study assessed the ability of the skeletal muscle of patients with COPD to adapt to individualized exercise training at the gas exchange threshold ( GET ) METHODS : Fourteen patients ( 8 in a training group and 6 controls ) performed the following exercise tests before and after a 3-week training period : an incremental exercise test , maximal voluntary contraction of the quadriceps , and three endurance tests consisting of dynamic contractions of the quadriceps until exhaustion . These endurance tests , characterized by three different power outputs , were used to determine muscle limit times and critical power . RESULTS The results showed that training increased exercise tolerance ( + 11 % for symptom limited peak oxygen consumption ( VO2 sl ] , P < 0.05 ) , maximum voluntary contraction ( + 8 % , P < 0.05 ) , limit times ( from + 45 % to + 161 % , P < 0.05 ) and critical power ( + 39 % , P < 0.05 ) . CONCLUSIONS These findings indicate greater muscle strength and endurance after training in COPD patients and suggest better muscular recruitment and improved oxidative capacity in the exercising muscles . The sharp differences in the magnitude of VO2 sl and limit times suggest that the kinetics of peripheral and central changes in response to training are different . In conclusion , peripheral muscle performance can be increased rapidly in response to an individualized training program at the GET in COPD patients BACKGROUND Most patients with severe COPD are limited by dyspnea and are obliged to exercise at low intensity . Even those undergoing training do not usually have increased peak oxygen uptake ( Vo2 ) . One-legged exercise , at half the load of two-legged exercise , places the same metabolic dem and s on the targeted muscles but reduces the ventilatory load , enabling patients to increase work capacity . The purpose of this study was to determine whether one-legged exercise training would improve aerobic capacity compared with two-legged training in stable patients with COPD . METHODS Eighteen patients with COPD ( mean FEV(1 ) , 38 + /- 17 % of predicted [ + /- SD ] ) were r and omized to two groups after completing an incremental exercise test . Both trained on a stationary cycle for 30 min , 3 d/wk , for 7 weeks Output:	Quadriceps endurance is reduced in individuals with COPD compared with healthy control subjects , independent of the type of task performed
MS22594	*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 contribution of sentinel-node biopsy to outcomes in patients with newly diagnosed melanoma . METHODS Patients with a primary cutaneous melanoma were r and omly assigned to wide excision and postoperative observation of regional lymph nodes with lymphadenectomy if nodal relapse occurred , or to wide excision and sentinel-node biopsy with immediate lymphadenectomy if nodal micrometastases were detected on biopsy . RESULTS Among 1269 patients with an intermediate-thickness primary melanoma , the mean ( + /-SE ) estimated 5-year disease-free survival rate for the population was 78.3+/-1.6 % in the biopsy group and 73.1+/-2.1 % in the observation group ( hazard ratio for recurrence[corrected ] , 0.74 ; 95 % confidence interval [ CI ] , 0.59 to 0.93 ; P=0.009 ) . Five-year melanoma-specific survival rates were similar in the two groups ( 87.1+/-1.3 % and 86.6+/-1.6 % , respectively ) . In the biopsy group , the presence of metastases in the sentinel node was the most important prognostic factor ; the 5-year survival rate was 72.3+/-4.6 % among patients with tumor-positive sentinel nodes and 90.2+/-1.3 % among those with tumor-negative sentinel nodes ( hazard ratio for death , 2.48 ; 95 % CI , 1.54 to 3.98 ; P<0.001 ) . The incidence of sentinel-node micrometastases was 16.0 % ( 122 of 764 patients ) , and the rate of nodal relapse in the observation group was 15.6 % ( 78 of 500 patients ) . The corresponding mean number of tumor-involved nodes was 1.4 in the biopsy group and 3.3 in the observation group ( P<0.001 ) , indicating disease progression during observation . Among patients with nodal metastases , the 5-year survival rate was higher among those who underwent immediate lymphadenectomy than among those in whom lymphadenectomy was delayed ( 72.3+/-4.6 % vs. 52.4+/-5.9 % ; hazard ratio for death , 0.51 ; 95 % CI , 0.32 to 0.81 ; P=0.004 ) . CONCLUSIONS The staging of intermediate-thickness ( 1.2 to 3.5 mm ) primary melanomas according to the results of sentinel-node biopsy provides important prognostic information and identifies patients with nodal metastases whose survival can be prolonged by immediate lymphadenectomy . ( Clinical Trials.gov number , NCT00275496 [ Clinical Trials.gov ] . ) Analysing specific non-fatal events in isolation may lead to spurious conclusions about efficacy unless the events considered are combined with all-cause mortality . The use of combined endpoints has therefore become widespread , at least in cardiovascular disease trials . Combining all-cause mortality with selected non-fatal events is useful because event-free survival , an important criterion in therapy evaluation , is addressed in this manner . In many clinical trials , symptoms , signs or para clinical measures ( for example , blood pressure , exercise duration , quality of life scores ) are used as endpoints . If the patient died before the endpoint was measured , or it was otherwise not possible to perform follow-up assessment s as planned , the effect of treatment on these endpoints may be distorted if the patients concerned are ignored in the analysis . Examples are given of how distortion can be avoided by including all patients r and omized in an analysis that uses a ranked combined endpoint based both on clinical events and on para clinical measures . A distinction is made between a pseudo intention-to-treat analysis that disregards study medication status at the time of endpoint assessment but is confined to patients with data , and a true intention-to-treat analysis that takes into account all patients r and omized based on a ranked combined endpoint BACKGROUND This study addressed the question of whether limited surgery for primary malignant melanoma with a 2-cm margin is as good as a 5-cm margin . An up date of a 16-year follow-up is provided . METHODS Nine European Centers , over a period of 5 years , prospect ively r and omized 337 patients with melanoma measuring less than 2.1 mm in thickness to undergo a local excision with either a 2-cm or a 5-cm margin . Three hundred twenty-six patients were eligible for statistical analysis . Excluded from the trial were patients older than 70 years ; those with melanomas from the toe , nail , or finger ; and those with acral-lentiginous melanoma . A separate r and omization was performed to independently test an adjuvant treatment with a nonspecific immunostimulant , isoprinosine , compared with observation . The median follow-up time was 192 months ( 16 years ) for the estimation of survival and disease recurrences . RESULTS There were 22 tumor recurrences in the 2-cm arm and 33 in the 5-cm arm . The median time to disease recurrence was 43 months and 37.6 months , respectively . The 10-year disease-free survival rates were 85 % for the group with a 2-cm margin and 83 % for the group with a 5-cm margin . There was no difference in the 10-year overall survival rates ( 87 % vs. 86 % ) . Isoprinosine did not demonstrate any activity in this setting . CONCLUSIONS The authors concluded that for melanoma less than 2.1-mm thick , a margin of excision of 2 cm is sufficient . A larger margin of 5 cm does not appear to have any impact on either the rate or the time to disease recurrence or on survival Abstract Background : In the past , radical margins of excision were prescribed for cutaneous melanoma based on preconceived notions rather than on hard clinical evidence . Methods : In a prospect i ve study of 742 patients with intermediate-thickness melanoma ( 1–4 mm ) , 470 patients with trunk or proximal extremity lesions were r and omized into a 2-or 4-cm margin . Patients with distal extremity or head and neck lesions ( n=272 ) received uniformly a 2-cm margin . Results : The overall rate of local recurrence was 3.8 % . This rate in the r and omized portion ( n=470 ) was 2.1 % for the 2-cm margin and 2.6 % for the 4-cm margin ( p=0.72 ) . A progressive increase in local recurrence rates was observed with thickness : 2.3 % for lesions 1.0–2.0 mm , 4.2 % for those 2.01–3.0 mm , and 11.7 % for those 3.01–4.0 mm thick ( p=0.001 ) . Local recurrence occurred in 1.5 % of those without ulceration and in 10.6 % of those with ulceration of the primary lesion ( p=0.001 ) . The local recurrence rate was not significantly affected by the margin of resection even among the thicker or ulcerated lesions . It also was not affected significantly by the method of closure of the primary site or management of the regional nodes , or the age or gender of the patients . Conclusions : A 2-cm margin is as effective as a 4-cm margin in local control and survival of intermediate-thickness melanomas . The local recurrence rate is significantly affected by the thickness of the primary lesion and the presence or not of ulceration BACKGROUND Controversy exists concerning the necessary margin of excision for cutaneous melanoma 2 mm or greater in thickness . METHODS We conducted a r and omized clinical trial comparing 1-cm and 3-cm margins . RESULTS Of the 900 patients who were enrolled , 453 were r and omly assigned to undergo surgery with a 1-cm margin of excision and 447 with a 3-cm margin of excision ; the median follow-up was 60 months . A 1-cm margin of excision was associated with a significantly increased risk of locoregional recurrence . There were 168 locoregional recurrences ( as first events ) in the group with 1-cm margins of excision , as compared with 142 in the group with 3-cm margins ( hazard ratio , 1.26 ; 95 percent confidence interval , 1.00 to 1.59 ; P=0.05 ) . There were 128 deaths attributable to melanoma in the group with 1-cm margins , as compared with 105 in the group with 3-cm margins ( hazard ratio , 1.24 ; 95 percent confidence interval , 0.96 to 1.61 ; P=0.1 ) ; overall survival was similar in the two groups ( hazard ratio for death , 1.07 ; 95 percent confidence interval , 0.85 to 1.36 ; P=0.6 ) . CONCLUSIONS A 1-cm margin of excision for melanoma with a poor prognosis ( as defined by a tumor thickness of at least 2 mm ) is associated with a significantly greater risk of regional recurrence than is a 3-cm margin , but with a similar overall survival rate BACKGROUND A prospect i ve , multi-institutional , r and omized surgical trial involving 486 localized melanoma patients was conducted to determine whether excision margins for intermediate-thickness melanomas ( 1.0 to 4.0 mm ) could be safely reduced from the st and ard 4-cm radius . METHODS Patients with 1- to 4-mm-thick melanomas on the trunk or proximal extremities were r and omly assigned to receive either a 2- or 4-cm surgical margin . RESULTS The median follow-up time was 6 years . The local recurrence rate was 0.8 % for 2-cm margins and 1.7 % for 4-cm margins ( p value not significant [ NS ] ) . The rates of in-transit metastases were 2.1 % and 2.5 % , respectively ( p = NS ) . Of the six patients with local recurrences , five have died . Recurrence rates did not correlate with surgical margins , even among stratified thickness groups . The overall 5-year survival rate was 79.5 % for the 2-cm margin patients and 83.7 % for the 4-cm margin patients ( p = NS ) . The need for skin grafting was reduced from 46 % with 4-cm surgical margins to 11 % with 2-cm surgical margins ( p < 0.001 ) . The hospital stay was shortened from 7.0 days for patients receiving 4-cm surgical margins to 5.2 days for those receiving 2-cm margins ( p = 0.0001 ) . This reduction was largely due to reduced need for skin grafting , since the hospital stay for those who had a skin graft was 2.5 days longer than that for those who had a primary wound closure ( p < 0.01 ) . CONCLUSION Margins of excision can be safely reduced to 2 cm for patients with intermediate-thickness melanomas . The narrower margins significantly reduced the need for skin grafting and shortened the hospital stay The traditional surgical treatment for primary malignant melanoma has often been a wide excision with a margin of about 5 cm . Since the risk of local recurrences is dependent on tumor thickness , thin tumors ( < 1 mm ) have routinely been excised with a narrow margin . For thick tumors , the optimal resection margin is controversial , and can be determined only by prospect i ve , r and omized trials A quality -of-life study was carried out to test the hypothesis that melanoma patients treated with a 3-cm margin of excision suffer greater impairment of their quality of life than those treated with a 1-cm margin . The secondary aim was to determine the predictors of a poor patient perception of their excision scar . A postal question naire study was carried out using Hospital Anxiety and Depression ( HAD ) , Psychosocial Adjustment of Illness Scale-Self-Report ( PAIS-SR ) , Medical Outcomes Survey-Short Form 36 ( MOS-SF36 ) , and the Cassileth Scar question naires . Data were collected from 426 of the 537 patients who were mailed the question naires ( response rate 79 % ) . Fourteen percent had clinical ly significant anxiety and 5 % had significant depression . A poor attitude toward quality of health care was associated with youth . Patients treated with a 3-cm margin excision had significantly poorer mental and physical function 1 mo after surgery , which disappeared within 6 mo . The greater difficulties experienced by the 3-cm margin group were particularly in their domestic , sexual , and social roles . Women , younger patients , those with poor physical and mental function after surgery , and those treated by a 3-cm margin were more likely to report a poorer perception of their scar . The poorer scar perception of patients in the 3-cm group persisted throughout the study period . Use of a 3-cm margin of excision for melanoma is associated with significantly more morbidity than use of a 1-cm margin , but this effect disappears in 6 mo . Patients treated by 3-cm excision were more likely , however , to have a persistent poor view of their scar . Youth and being female were also predictors of poor perception of the scar INTRODUCTION The incidence of melanoma has increased fivefold during the past three decades . Melanoma can no longer be classified as rare ; rather , it is now one of the more frequent tumors . METHODS Recommendations for the diagnosis and treatment of melanoma are laid out in the interdisciplinary S2 guidelines of the German Cancer Society , upon which the present review is based . The goal of this article is to present the clinical core recommendations for treatment in all disease stages . RESULT Output:	This systematic review summarises the evidence regarding width of excision margins for primary cutaneous melanoma . The summary estimate for recurrence free survival favoured wide excision [ Hazard Ratio 1.13 ; P = 0.06 ; 95 % confidence interval 0.99 to 1.28 ] but again the result did not reach statistical significance ( P < 0.05 level).Current r and omised trial evidence is insufficient to address optimal excision margins for primary cutaneous melanoma
MS22595	*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 each of 14 patients , one bilateral occlusal carious lesion was sealed and the other lesion was left open as a control . The control lesions showed patterns of sudden increases in cavity depth , as well as evidence of being active bacteriologically ; whereas , with one exception , the sealed lesions were inactive bacteriologically . The residual carious material in the sealed lesions suggested a complete cessation of the carious process . No clinical or radiologic signs were seen to suggest that the health of the sealed tooth had been compromised Results of a 3-year clinical trial of Delton fissure sealant resin are reported . 41 % of first molar fissures remained fully sealed after 3 years . Significant differences were found between the levels of resin retention produced by the two operators and retention was significantly better on m and ibular molars than on maxillary molars . In a separate group of 11-year-old children 77 % of fissures were full)’sealed after 3 years The purpose of this study was to evaluate the retention of fissure sealants , applied with 4 different combinations of isolation and preparation of occlusal surface . In 95 children aged 7 - 8 years , having all four first permanent molars fully erupted and caries free , a chemically initiated tinted fissure sealant was placed with the following 4 different methods in every child . 1 ) Tooth 16 : Cotton rolls isolation and cleaning of occlusal surface using a bristle brush and non-fluori date d paste . 2 ) Tooth 26 : Rubber dam isolation and mechanical preparation of pits and fissures using a round bur No. 0 in a slow h and -piece . 3 ) Tooth 36 : Rubber dam isolation and cleaning of occlusal surface using a bristle brush and non-fluori date d paste . 4 ) Tooth 46 : Isolation with cotton rolls and mechanical preparation of pits and fissures using a round bur No. 0 in a slow h and -piece . Eighty children were available for re-examination 4 years later ( 320 teeth ) . The 4 methods of application showed the following success rates of full retention : 1 ) 81 % 2 ) 88 % 3 ) 91 % 4 ) 93 % . Although statistical analysis of the results revealed only marginal statistically significant difference among the four different methods of application ( p = 0.091 ) , there was statistical significant difference ( p = 0.031 ) between methods 1 and 4 . No differences were detected among the remaining methods . The present trial revealed best sealant retention using a combination of cotton rolls isolation and mechanical preparation of the occlusal surface . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND While national surveys have found that African-Americans have a higher prevalence and severity of dental caries than white-Americans , there are only a few descriptive studies of the prevalence and severity of dental caries in low-income urban African-Americans . OBJECTIVES This study assessed the prevalence , severity and determinants of dental caries , using the International Caries Detection and Assessment System ( ICDAS ) . METHODS A representative sample of low-income families ( a caregiver and a child aged 0 - 5 years ) was selected from low-income census tracts in the city of Detroit , Michigan . Of the 12,655 r and omly selected housing units , 10,695 were occupied and 9781 were successfully contacted ( 91.5 % ) . There were 1386 families with eligible children in the contacted households ; and of those , 1021 were interviewed and examined at a permanent examination center organized for this study . This represents an overall response rate of 73.7 % . At the center , trained staff interviewed the main caregivers of the selected children , and trained and calibrated dentists examined the caregiver and her/his child . Data used in this study included information gathered from the social , behavioral and parenting question naires , the Block Food Frequency Question naire ( total sugar intake ) , and data collected from community and census data bases . RESULTS Over 90 % of the adults ( ages 14 - 70 years , average 29.3 ) had at least one noncavitated carious lesion and 82.2 % had at least one primary cavitated lesion . Negative binomial regression models found that the age of caregivers and the number of churches in neighborhoods were negatively associated with the number of noncavitated tooth surfaces . Cavitated tooth surfaces were positively associated with age , oral hygiene status , being worried about teeth , a recent visit to a dentist , and the number of grocery stores in the neighborhoods . However , the number of cavitated tooth surfaces was negatively associated with preventive dental visits , positive rating of oral health status and the number of dentists in a community . CONCLUSIONS Dental caries , especially at the noncavitated stage , is highly prevalent in low-income African-American adults in Detroit . A significant increase in the mean number of missing teeth was observed after the age of 34 years . This study found that different individual , social , and community risk indicators were associated with noncavitated versus cavitated tooth surfaces OBJECTIVES This study compared the effectiveness of two different tooth-cleaning techniques on clinical sealant retention . METHODS Seventy-four children in second and third grade s at an elementary school in the rural town of Waverly , Tennessee , had sealants applied to four , noncarious , fully erupted , first permanent molar teeth . The teeth had been cleaned using a brush attached to a rotary instrument with fluori date d prophy paste , versus a toothbrush without paste ( dry brushing ) . A split-mouth design was used , whereby one side ( upper and lower ) of the mouth was subject to one tooth-cleaning technique while the opposite side received the other technique . RESULTS Twelve months after a single application of pit and fissure sealant , 63 children were available for recall . Exactly 252 teeth were examined and overall retention was high , with approximately 98 percent of sealants retained . Although the greatest loss of sealant occurred with the rotary instrument technique , the difference in proportions of missing sealant between techniques was not statistically significant . CONCLUSIONS In this study , the tooth-cleaning technique of dry brushing with a toothbrush as a preparatory step in the sealant procedure yielded high clinical sealant retention at 12 months . This retention was comparable to that observed with rotary instrumentation . This finding suggests that dry brushing by the operator may be an acceptable alternative to using a rotary instrument with brush and paste Output:	RESULTS The evidence supports recommendations to seal sound surfaces and noncavitated lesions , to use visual assessment to detect surface cavitation , to use a toothbrush or h and piece prophylaxis to clean tooth surfaces , and to provide sealants to children even if follow-up can not be ensured . CLINICAL IMPLICATION S These recommendations are consistent with the current state of the science and provide appropriate guidance for sealant use in SBSPs .
MS22596	*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 A substantial minority of neurologically normal children with sickle cell disease have lesions consistent with cerebral infa rct ion as seen on magnetic resonance imaging ( MRI ) . OBJECTIVES To determine if transfusion therapy affects the rate at which silent infa rcts develop and to evaluate the contribution of MRI of the brain to stroke prediction by transcranial Doppler ( TCD ) ultrasonography . STUDY DESIGN Children with elevated TCD ultrasonographic velocity were r and omized to receive long-term transfusion therapy or st and ard care . Magnetic resonance imaging of the brain was obtained at r and omization , annually , and with clinical neurologic events . The risk for new silent lesions and /or stroke was compared for each treatment arm . RESULTS Among the 37 % of subjects with silent infa rcts , those receiving st and ard care were significantly more likely to develop new silent lesions or stroke than were those who received transfusion therapy . For subjects receiving st and ard care , those with lesions at baseline were significantly more likely to develop stroke or new silent lesions than those whose MRI studies showed no abnormality . CONCLUSIONS Transfusion therapy lowers the risk for new silent infa rct or stroke for children having both abnormal TCD ultrasonographic velocity and silent infa rct . However , those with both abnormalities who are not provided transfusion therapy are at higher risk for developing a new silent infa rct or stroke than are those whose initial MRI showed no abnormality . The finding of a silent infa rct reinforces the need for TCD ultrasonographic screening and consideration of transfusion therapy if the abnormalities are seen . Similarly , elevated TCD ultrasonographic velocity warrants MRI of the brain because children with both abnormalities seem to be at increased risk for developing new silent infa rct or stroke Although long-term transfusion therapy is at least 90 % effective in preventing recurrent strokes after an initial cerebrovascular accident in patients with sickle cell disease , it is unknown how long transfusion therapy should be continued . To address this question , we prospect ively discontinued transfusions in 10 patients with sickle cell disease whose median duration of transfusion therapy after an initial stroke was 9 1/2 years ( range 5 to 12 years ) . Before the transfusions were discontinued , patients were examined by cerebral angiography , magnetic resonance imaging of the head , neuropsychologic testing , electroencephalography , and a complete neurologic examination . Within 12 months after transfusion therapy was stopped , 5 of 10 patients had had an ischemic event . Three events caused relatively mild deficits in the same areas as those originally affected . Two were associated with massive intracranial hemorrhage , including one on the contralateral side of original involvement . An additional patient died suddenly of unknown causes . Of the four remaining patients , three declined to resume transfusion and are relatively well at greater than or equal to 18 months after therapy was stopped . The studies performed before transfusions were stopped were not predictive of recurrent stroke . The risk of recurrent cerebrovascular accident in this group was significantly greater than the estimated risk of 10 % in patients who are receiving long-term transfusion therapy ( p = 0.002 ) . This adverse outcome suggests that patients with sickle cell disease who have had a stroke must receive long-term transfusion indefinitely or a suitable therapeutic alternative must be devised OBJECTIVE The Stroke Prevention Trial ( STOP ) demonstrated that chronic transfusion is highly effective in reducing the risk of stroke in children with sickle-cell disease and an abnormal transcranial Doppler ultrasonography examination result . Our objective was to determine whether chronic transfusion therapy reduces the incidence of pain and acute chest syndrome . METHODS During STOP , 130 children with sickle-cell anemia or sickle beta(0)-thalassemia and abnormal transcranial Doppler ultrasonography examination result were r and omly assigned to chronic transfusion ( n = 63 ) or observation ( n = 67 ) . In addition to monitoring for stroke , nonneurologic sickle-cell complications were identified and recorded . RESULTS Mean age at STOP study entry was 8.3 + /- 3.3 years , and mean follow-up was 19.6 + /- 6.5 months . Hospitalization rates ( based on intent-to-treat analysis ) for acute chest syndrome were 4.8 and 15.3 per 100 patient-years ( P = .0027 ) and for pain were 16.2 and 27.6 per 100 patient-years ( P = .13 ) in the chronic transfusion and observed groups , respectively . If analyzed according to treatment actually received , the difference in pain rate becomes significant ( 9.7 vs 27.1 events per 100 patient-years , P = .014 ) , and transfusion remains protective from acute chest syndrome ( 2.2 vs 15.7 events per 100 patient-years , P = .0001 ) . CONCLUSIONS Compliance with aggressive chronic transfusion reduces the frequency of acute chest syndrome and pain episodes BACKGROUND Blood transfusions prevent recurrent stroke in children with sickle cell anemia , but the value of transfusions in preventing a first stroke is unknown . We used transcranial Doppler ultrasonography to identify children with sickle cell anemia who were at high risk for stroke and then r and omly assigned them to receive st and ard care or transfusions to prevent a first stroke . METHODS To enter the study , children with sickle cell anemia and no history of stroke had to have undergone two transcranial Doppler studies that showed that the time-averaged mean blood-flow velocity in the internal carotid or middle cerebral artery was 200 cm per second or higher . The patients were r and omly assigned to receive st and ard care or transfusions to reduce the hemoglobin S concentration to less than 30 percent of the total hemoglobin concentration . The incidence of stroke ( cerebral infa rct ion or intracranial hemorrhage ) was compared between the two groups . RESULTS A total of 130 children ( mean [ + /-SD ] age , 8.3+/-3.3 years ) were enrolled ; 63 were r and omly assigned to receive transfusions and 67 to receive st and ard care . At base line , the transfusion group had a slightly lower mean hemoglobin concentration ( 7.2 vs. 7.6 g per deciliter , P=0.001 ) and hematocrit ( 20.4 vs. 21.7 percent , P=0.002 ) . Ten patients dropped out of the transfusion group , and two patients crossed over from the st and ard-care group to the transfusion group . There were 10 cerebral infa rct ions and 1 intracerebral hematoma in the st and ard-care group , as compared with 1 infa rct ion in the transfusion group -- a 92 percent difference in the risk of stroke ( P<0.001 ) . This result led to the early termination of the trial . CONCLUSIONS Transfusion greatly reduces the risk of a first stroke in children with sickle cell anemia who have abnormal results on transcranial Doppler ultrasonography OBJECTIVE To determine the effect of a transfusion program on risk of stroke recurrence in children with sickle cell disease . DESIGN The clinical course and experience with transfusion therapy at eight centers were review ed for subjects whose initial stroke occurred after January 1988 . RESULTS Sixty subjects were observed for 191.7 patient-years . Eight had a single recurrent stroke ( two intracranial hemorrhages and six infa rct ions ) for a prevalence of 13.3 % , or one recurrence for each 24 patient-years of observation . Thirteen subjects had 15 transient neurologic events ; two of these had subsequent strokes , but the overall risk was similar for those who did and those did not have transient events . Hemoglobin S levels were greater than the desired maximum of 30 % at the time of 7 of 16 transient events and five of six recurrent infa rct ions . The stroke recurrence rate was similar to those in previous reports of children receiving long-term transfusion therapy but significantly less than that reported for children who did not receive transfusions ( p < 0.001 ) . CONCLUSIONS We conclude that maintenance of hemoglobin S at a level less than 30 % appears to be effective in reducing the rate of recurrent infa rct ion but does not prevent transient neurologic events . Transient neurologic events are common but do not appear to be related to recurrent stroke The stroke prevention study in sickle cell disease ( STOP ) demonstrated a 90 % reduction in stroke risk with transfusion among patients with time-averaged mean cerebral blood velocity ( TAMV ) of 200 cm/s or more as measured by transcranial Doppler ( TCD ) . In STOP , 232 brain magnetic resonance angiograms ( MRAs ) were performed on 100 patients , 47 in the transfusion arm and 53 in the st and ard care arm . Baseline MRA findings were interpreted as normal in 75 patients and as indicating mild stenosis in 4 patients and severe stenosis in 21 patients . Among 35 patients who underwent magnetic resonance angiography within 30 days of r and om assignment , the TAMV was significantly higher in 7 patients with severe stenosis compared with 28 patients with normal MRA findings or mild stenosis ( 276.7 + /- 34 vs 215 + /- 15.6 cm/s ; P<.001 ) . In the st and ard care arm , 4 of 13 patients with abnormal MRA findings had strokes compared with 5 of 40 patients with normal MRA findings ( P=.03 ) . In this arm , TAMV became normal ( less than 170 cm/s ) or conditional ( 170 - 199 cm/s ) in 26 of 38 patients with normal or mildly abnormal baseline MRA but remained abnormal in 8 of 10 patients with severely abnormal baseline MRA . These results suggest that TCD often detects flow abnormalities indicative of stroke risk before MRA lesions become evident . Furthermore , patients with abnormal MRA findings and higher TCD velocities are at higher risk for stroke , and their cerebral TAMVs are unlikely to decrease without transfusion Stroke occurs in 7 - 8 % of children with Sickle Cell Disease ( Hb SS ) and is a major cause of morbidity . Rates of recurrence have been reduced from 46 - 90 % to less than 10 % through chronic blood transfusions . Prevention of first stroke , however , would be preferable because even one stroke can cause irreversible brain injury . Transcranial Doppler ( TCD ) ultrasound can detect arterial blood flow rates associated with subsequent stroke risk . By combining TCD screening and a potentially effective treatment , first stroke may be prevented . The Stroke Prevention Trial in Sickle Cell Anemia ( STOP ) is the first stroke prevention trial in Hb SS and the first r and omized , controlled use of transfusion in Hb SS . This multi-center trial is design ed to test whether reducing sickle hemoglobin to 30 % or less with periodic blood transfusions will reduce first-time stroke by at least 70 % compared to st and ard care . Primary endpoints will be clinical ly evident symptoms of cerebral infa rct ion with consistent findings on Magnetic Resonance Imaging and Angiography ( MRI/MRA ) or symptomatic intracranial hemorrhage . Secondary endpoints will be asymptomatic brain lesions detected by MRI in brain areas not involved in primary endpoints . The design calls for a 6-month start-up interval , 18 months of TCD screening and r and omization , and observation for stroke from entry through month 54 . Key features of the trial are st and ardized TCD and MRI/MRA protocol s interpreted blindly , and blinded adjudication of endpoints . The sample size ( 60 per treatment group ) is based on prospect i ve data relating TCD velocity to risk of stroke . A time-averaged mean velocity of > or = 200 cm/sec is associated with a 46 % risk of cerebral infa rct ion over 39 months . The sample size is sufficient to detect 70 % reduction in the primary endpoint at 90 % power . This trial will determine if transfusion is effective in the primary prevention of stroke . Secondary aims may further the underst and ing of the effects of transfusion on the brain and guide future research into cerebrovascular disease in Hb SS Purpose Chronic red cell transfusion has been used for prevention of recurrent stroke in patients with sickle cell disease for three decades , and its effectiveness in primary prevention was recently shown . Iron overload , the inevitable result of chronic transfusion , is commonly monitored with serum ferritin concentration . Patients and Methods Sixty-one patients at high risk for stroke received chronic transfusion in a clinical trial of stroke prevention . A serum ferritin level of less than 500 ng/mL was required for study entry . Ferritin levels were obtained quarterly . Fifty patients who had four or more ferritin measurements were included in this analysis . Transfusions were administered as exchange or simple , with washed , reconstituted , or packed red blood cells , at the discretion of the site investigator . Results Serum ferritin levels increased linearly with cumulative transfusion volume during the first four ferritin measurements , but the rate of increase varied widely among patients . Rates of increase varied similarly among 23 patients who received exclusively simple transfusion with packed red cells and in five patients who received exchange transfusions . Thirty-two patients received a total transfusion volume of more than 250 mL/kg . Ferritin continued to increase linearly after the first four measurements in 14 , but the remaining 1 Output:	REVIEW ER 'S CONCLUSIONS While the included study demonstrated a significantly reduced risk of stroke in patients receiving regular blood transfusions , the degree of risk must be balanced against the burden of a chronic transfusion regime .
MS22597	*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 Transcatheter aortic valve implantation ( TAVI ) has gained rapid acceptance for patients with severe aortic stenosis ( AS ) at high surgical risk for conventional valve replacement . Although TAVI is now a relatively mature technique , limited data about long-term valvular function are available . Our aim was to report the five-year echocardiographic data evaluating valve performance from three early European feasibility studies design ed to assess the safety and effectiveness of the first-generation balloon-exp and able transcatheter heart valve ( SAPIEN THV ) . METHODS AND RESULTS A total of 410 patients were enrolled in the following single-arm , non-r and omised , prospect i ve multicentre clinical studies : REVIVE II , TRAVERCE and PARTNER EU . Five-year follow-up was completed in 114 surviving patients . Mean patient age was 82.3±5.6 years ; 63.4 % were female . The mean logistic EuroSCORE was 28.4±13.3 % . NYHA Class III/IV was reported in 92.5 % . At five years , the mean effective orifice area ( EOA ) was 1.6±0.6 cm² ( n=34 ) and the mean gradient was 11.7±5.4 mmHg ( n=39 ) . In paired patient data , the difference between discharge and five-year EOA was 0.1±0.7 cm² ( p=0.3956 ) and mean gradient was 2.2±5.7 mmHg ( p=0.0900 ) . At discharge and five years , respectively , aortic regurgitation ( AR ) was evaluated as none/trace in 66.6 % ( n=162/243 ) and 55.3 % ( n=19/38 ) , mild in 28.4 % ( n=69/243 ) and 39.5 % ( n=15/38 ) , and moderate in 4.9 % ( n=12/243 ) and 5.3 % ( n=2/38 ) . No severe AR was reported at follow-up . Valve thrombosis was observed in three patients and occurred within one year . No valve-related explants and no case of structural valve deterioration have been reported . CONCLUSIONS Long-term echocardiographic outcomes in high-risk patients with severe AS suggest stable haemodynamic function of first-generation balloon-exp and able SAPIEN THVs at five years , with no worsening of AR severity over time BACKGROUND Little is known about the incidence of prosthesis-patient mismatch ( PPM ) and its impact on outcomes after transcatheter aortic valve replacement ( TAVR ) . OBJECTIVES The objectives of this study were : 1 ) to compare the incidence of PPM in the TAVR and surgical aortic valve replacement ( SAVR ) r and omized control trial ( RCT ) arms of the PARTNER ( Placement of AoRTic TraNscathetER Valves ) I Trial cohort A ; and 2 ) to assess the impact of PPM on regression of left ventricular ( LV ) hypertrophy and mortality in these 2 arms and in the TAVR nonr and omized continued access ( NRCA ) registry cohort . METHODS The PARTNER Trial cohort A r and omized patients 1:1 to TAVR or bioprosthetic SAVR . Postoperative PPM was defined as absent if the indexed effective orifice area ( EOA ) was > 0.85 cm(2)/m(2 ) , moderate if the indexed EOA was ≥0.65 but ≤0.85 cm(2)/m(2 ) , or severe if the indexed EOA was < 0.65 cm(2)/m(2 ) . LV mass regression and mortality were analyzed using the SAVR- RCT ( n = 270 ) , TAVR- RCT ( n = 304 ) , and TAVR-NRCA ( n = 1,637 ) cohorts . RESULTS The incidence of PPM was 60.0 % ( severe : 28.1 % ) in the SAVR- RCT cohort versus 46.4 % ( severe : 19.7 % ) in the TAVR- RCT cohort ( p < 0.001 ) and 43.8 % ( severe : 13.6 % ) in the TAVR-NRCA cohort . In patients with an aortic annulus diameter < 20 mm , severe PPM developed in 33.7 % undergoing SAVR compared with 19.0 % undergoing TAVR ( p = 0.002 ) . PPM was an independent predictor of less LV mass regression at 1 year in the SAVR- RCT ( p = 0.017 ) and TAVR-NRCA ( p = 0.012 ) cohorts but not in the TAVR- RCT cohort ( p = 0.35 ) . Severe PPM was an independent predictor of 2-year mortality in the SAVR- RCT cohort ( hazard ratio [ HR ] : 1.78 ; p = 0.041 ) but not in the TAVR- RCT cohort ( HR : 0.58 ; p = 0.11 ) . In the TAVR-NRCA cohort , severe PPM was not a predictor of 1-year mortality in all patients ( HR : 1.05 ; p = 0.60 ) but did independently predict mortality in the subset of patients with no post-procedural aortic regurgitation ( HR : 1.88 ; p = 0.02 ) . CONCLUSIONS In patients with severe aortic stenosis and high surgical risk , PPM is more frequent and more often severe after SAVR than TAVR . Patients with PPM after SAVR have worse survival and less LV mass regression than those without PPM . Severe PPM also has a significant impact on survival after TAVR in the subset of patients with no post-procedural aortic regurgitation . TAVR may be preferable to SAVR in patients with a small aortic annulus who are susceptible to PPM to avoid its adverse impact on LV mass regression and survival . ( The PARTNER Trial : Placement of AoRTic TraNscathetER Valve Trial ; NCT00530894 ) Objective To determine the frequency of survival , stroke , atrial fibrillation , structural valve deterioration , and length of hospital stay after surgical replacement of an aortic valve ( SAVR ) with a bioprosthetic valve in patients with severe symptomatic aortic stenosis . Design Systematic review and meta- analysis of observational studies . Data sources Medline , Embase , PubMed ( non- Medline records only ) , Cochrane Data base of Systematic Review s , and Cochrane CENTRAL from 2002 to June 2016 . Study selection Eligible observational studies followed patients after SAVR with a bioprosthetic valve for at least two years . Methods Review ers , independently and in duplicate , evaluated study eligibility , extracted data , and assessed risk of bias for patient important outcomes . We used the GRADE system to quantify absolute effects and quality of evidence . Published survival curves provided data for survival and freedom from structural valve deterioration , and r and om effect models provided the framework for estimates of pooled incidence rates of stroke , atrial fibrillation , and length of hospital stay . Results In patients undergoing SAVR with a bioprosthetic valve , median survival was 16 years in those aged 65 or less , 12 years in those aged 65 to 75 , seven years in those aged 75 to 85 , and six years in those aged more than 85 . The incidence rate of stroke was 0.25 per 100 patient years ( 95 % confidence interval 0.06 to 0.54 ) and atrial fibrillation 2.90 per 100 patient years ( 1.78 to 4.79 ) . Post-SAVR , freedom from structural valve deterioration was 94.0 % at 10 years , 81.7 % at 15 years , and 52 % at 20 years , and mean length of hospital stay was 12 days ( 95 % confidence interval 9 to 15 ) . Conclusion Patients with severe symptomatic aortic stenosis undergoing SAVR with a bioprosthetic valve can expect only slightly lower survival than those without aortic stenosis , and a low incidence of stroke and , up to 10 years , of structural valve deterioration . The rate of deterioration increases rapidly after 10 years , and particularly after 15 years BACKGROUND In patients with severe aortic stenosis at increased risk for surgery , self-exp and ing transcatheter aortic valve replacement ( TAVR ) is associated with improved 2-year survival compared with surgery . OBJECTIVES This study sought to determine whether this clinical benefit was sustained over time . METHODS Patients with severe aortic stenosis deemed at increased risk for surgery by a multidisciplinary heart team were r and omized 1:1 to TAVR or open surgical valve replacement ( SAVR ) . Three-year clinical and echocardiographic outcomes were obtained in those patients with an attempted procedure . RESULTS A total of 797 patients underwent r and omization at 45 U.S. centers ; 750 patients underwent an attempted procedure . Three-year all-cause mortality or stroke was significantly lower in TAVR patients ( 37.3 % vs. 46.7 % in SAVR ; p = 0.006 ) . Adverse clinical outcome components were also reduced in TAVR patients compared with SAVR patients , including all-cause mortality ( 32.9 % vs. 39.1 % , respectively ; p = 0.068 ) , all stroke ( 12.6 % vs. 19.0 % , respectively ; p = 0.034 ) , and major adverse cardiovascular or cerebrovascular events ( 40.2 % vs. 47.9 % , respectively ; p = 0.025 ) . At 3 years aortic valve hemodynamics were better with TAVR patients ( mean aortic valve gradient 7.62 ± 3.57 mm Hg vs. 11.40 ± 6.81 mm Hg in SAVR ; p < 0.001 ) , although moderate or severe residual aortic regurgitation was higher in TAVR patients ( 6.8 % vs. 0.0 % in SAVR ; p < 0.001 ) . There was no clinical evidence of valve thrombosis in either group . CONCLUSIONS Patients with severe aortic stenosis at increased risk for surgery had improved 3-year clinical outcomes after TAVR compared with surgery . Aortic valve hemodynamics were more favorable in TAVR patients without differences in structural valve deterioration . ( Safety and Efficacy Study of the Medtronic CoreValve ( ® ) System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement ; NCT01240902 ) BACKGROUND Scarce data exist on the incidence of and factors associated with valve hemodynamic deterioration ( VHD ) after transcatheter aortic valve replacement ( TAVR ) . OBJECTIVES This study sought to determine the incidence , timing , and predictors of VHD in a large cohort of patients undergoing TAVR . METHODS This multicenter registry included 1,521 patients ( 48 % male ; 80 ± 7 years of age ) who underwent TAVR . Mean echocardiographic follow-up was 20 ± 13 months ( minimum : 6 months ) . Echocardiographic examinations were performed at discharge , at 6 to 12 months , and yearly thereafter . Annualized changes in mean gradient ( mm Hg/year ) were calculated by dividing the difference between the mean gradient at last follow-up and the gradient at discharge by the time between examinations . VHD was defined as a ≥10 mm Hg increase in transprosthetic mean gradient during follow-up compared with discharge assessment . RESULTS The overall mean annualized rate of transprosthetic gradient progression during follow-up was 0.30 ± 4.99 mm Hg/year . A total of 68 patients met criteria of VHD ( incidence : 4.5 % during follow-up ) . The absence of anticoagulation therapy at hospital discharge ( p = 0.002 ) , a valve-in-valve ( TAVR in a surgical valve ) procedure ( p = 0.032 ) , the use of a 23-mm valve ( p = 0.016 ) , and a greater body mass index ( p = 0.001 ) were independent predictors of VHD . CONCLUSIONS There was a mild but significant increase in transvalvular gradients over time after TAVR . The lack of anticoagulation therapy , a valve-in-valve procedure , a greater body mass index , and the use of a 23-mm transcatheter valve were associated with higher rates of VHD post-TAVR . Further prospect i ve studies are required to determine whether a specific antithrombotic therapy post-TAVR may reduce the risk of VHD Output:	Importantly , the freedom from reoperation for valve dysfunction at 10 , 15 and 20 years was 94 % , 81.7 % and 52 % , respectively.1 Figure 1 Structural valve deterioration .
MS22598	*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 Despite the amount of online health information , there are several barriers that limit the Internet ’s adoption as a source of health information . One of these barriers is highlighted in conceptualizations of the digital divide which include the differential possession of Internet skills , or “ eHealth literacy ” . Most measures of Internet skills among population s at large use self- assessment s. The research discussed here applies a multifaceted definition of Internet skills and uses actual performance tests . Objective The purpose of this study was to assess how ready a sample of the general population is for eHealth . More specifically , four types of Internet skills were measured in a performance test in which subjects had to complete health-related assignments on the Internet . Methods From November 1 , 2009 , through February 28 , 2010 , 88 subjects participated in the study . Subjects were r and omly selected from a telephone directory . A selective quota sample was used divided over equal sub sample s of gender , age , and education . Each subject had to accomplish assignments on the Internet . The Internet skills accounted for were categorized as operational ( basic skills to use the Internet ) , formal ( navigation and orientation ) , information ( finding information ) , and strategic ( using the information for personal benefits ) . The tests took approximately 1.5 hours and were conducted in a University office , making the setting equally new for all . Successful completion and time spent on the assignments — the two main outcomes —were directly measured by the test leader . Results The subjects successfully completed an average of 73 % ( 5.8/8 ) of the operational Internet skill tasks and an average of 73 % ( 2.9/4 ) of the formal Internet skill tasks . Of the information Internet skills tasks , an average of 50 % ( 1.5/3 ) was completed successfully and , of the strategic Internet skills tasks , 35 % ( 0.7/2 ) . Only 28 % ( 25/88 ) of the subjects were able to successfully complete all operational skills tasks , 39 % ( 34/88 ) all formal skills tasks , 13 % ( 11/88 ) all information skills tasks , and 20 % ( 18/88 ) both the strategic skill tasks . The time spent on the assignments varied substantially . Age and education were the most important contributors to the operational and formal Internet skills . Regarding the formal Internet skills , years of Internet experience also had some influence . Educational level of attainment was the most important contributor to the information and strategic Internet skills . Conclusions Although the amount of online health-related information and services is consistently growing , it appears that the general population lacks the skills to keep up . Most problematic appear to be the lack of information and strategic Internet skills , which , in the context of health , are very important . The lack of these skills is also problematic for members of younger generations , who are often considered skilled Internet users . This primarily seems to account for the operational and formal Internet skills . The results of the study strongly call for policies to increase the level of Internet skills Background eHealth literacy is defined as the ability of people to use emerging information and communications technologies to improve or enable health and health care . Objective The goal of this study was to explore whether literacy disparities are diminished or enhanced in the search for health information on the Internet . The study focused on ( 1 ) traditional digital divide variables , such as sociodemographic characteristics , digital access , and digital literacy , ( 2 ) information search processes , and ( 3 ) the outcomes of Internet use for health information purpose s. Methods We used a countrywide representative r and om-digital-dial telephone household survey of the Israeli adult population ( 18 years and older , N = 4286 ) . We measured eHealth literacy ; Internet access ; digital literacy ; sociodemographic factors ; perceived health ; presence of chronic diseases ; as well as health information sources , content , search strategies , and evaluation criteria used by consumers . Results Respondents who were highly eHealth literate tended to be younger and more educated than their less eHealth-literate counterparts . They were also more active consumers of all types of information on the Internet , used more search strategies , and scrutinized information more carefully than did the less eHealth-literate respondents . Finally , respondents who were highly eHealth literate gained more positive outcomes from the information search in terms of cognitive , instrumental ( self-management of health care needs , health behaviors , and better use of health insurance ) , and interpersonal ( interacting with their physician ) gains . Conclusions The present study documented differences between respondents high and low in eHealth literacy in terms of background attributes , information consumption , and outcomes of the information search . The association of eHealth literacy with background attributes indicates that the Internet reinforces existing social differences . The more comprehensive and sophisticated use of the Internet and the subsequent increased gains among the high eHealth literate create new inequalities in the domain of digital health information . There is a need to educate at-risk and needy groups ( eg , chronically ill ) and to design technology in a mode befitting more consumers Background Compared to females , males experience higher rates of chronic disease and mortality , yet few health promotion initiatives are specifically aim ed at men . Therefore , the aim of the ManUp Study is to examine the effectiveness of an IT-based intervention to increase the physical activity and nutrition behaviour and literacy in middle-aged males ( aged 35–54 years ) . Method / Design The study design was a two-arm r and omised controlled trial , having an IT-based ( applying website and mobile phones ) and a print-based intervention arm , to deliver intervention material s and to promote self-monitoring of physical activity and nutrition behaviours . Participants ( n = 317 ) were r and omised on a 2:1 ratio in favour of the IT-based intervention arm . Both intervention arms completed assessment s at baseline , 3 , and 9 months . All participants completed self-report assessment s of physical activity , sitting time , nutrition behaviours , physical activity and nutrition literacy , perceived health status and socio-demographic characteristics . A r and omly selected sub- sample in the IT-based ( n = 61 ) and print-based ( n = 30 ) intervention arms completed objective measures of height , weight , waist circumference , and physical activity as measured by accelerometer ( Actigraph GT3X ) . The average age of participants in the IT-based and print-based intervention arm was 44.2 and 43.8 years respectively . The majority of participants were employed in professional occupations ( IT-based 57.6 % , Print-based 54.2 % ) and were overweight or obese ( IT-based 90.8 % , Print-based 87.3 % ) . At baseline a lower proportion of participants in the IT-based ( 70.2 % ) group agreed that 30 minutes of physical activity each day is enough to improve health compared to the print-based ( 82.3 % ) group ( p = .026 ) . The IT-based group consumed a significantly lower number of serves of red meat in the previous week , compared to the print-based group ( p = .017 ) . No other significant between-group differences were observed at baseline . Discussion The ManUp Study will examine the effectiveness of an IT-based approach to improve physical activity and nutrition behaviour and literacy . Study outcomes will provide much needed information on the efficacy of this approach in middle aged males , which is important due to the large proportions of males at risk , and the potential reach of IT-based interventions .Trial registration Background Baby boomers and older adults , a subset of the population at high risk for chronic disease , social isolation , and poor health outcomes , are increasingly utilizing the Internet and social media ( Web 2.0 ) to locate and evaluate health information . However , among these older population s , little is known about what factors influence their eHealth literacy and use of Web 2.0 for health information . Objective The intent of the study was to explore the extent to which sociodemographic , social determinants , and electronic device use influences eHealth literacy and use of Web 2.0 for health information among baby boomers and older adults . Methods A r and om sample of baby boomers and older adults ( n=283 , mean 67.46 years , SD 9.98 ) participated in a cross-sectional , telephone survey that included the eHealth literacy scale ( eHEALS ) and items from the Health Information National Trends Survey ( HINTS ) assessing electronic device use and use of Web 2.0 for health information . An independent sample s t test compared eHealth literacy among users and non-users of Web 2.0 for health information . Multiple linear and logistic regression analyses were conducted to determine associations between sociodemographic , social determinants , and electronic device use on self-reported eHealth literacy and use of Web 2.0 for seeking and sharing health information . Results Almost 90 % of older Web 2.0 users ( 90/101 , 89.1 % ) reported using popular Web 2.0 websites , such as Facebook and Twitter , to find and share health information . Respondents reporting use of Web 2.0 reported greater eHealth literacy ( mean 30.38 , SD 5.45 , n=101 ) than those who did not use Web 2.0 ( mean 28.31 , SD 5.79 , n=182 ) , t 217.60=−2.98 , P=.003 . Younger age ( b=−0.10 ) , more education ( b=0.48 ) , and use of more electronic devices ( b=1.26 ) were significantly associated with greater eHealth literacy ( R 2 = .17 , R 2adj = .14 , F9,229=5.277 , P<.001 ) . Women were nearly three times more likely than men to use Web 2.0 for health information ( OR 2.63 , Wald= 8.09 , df=1 , P=.004 ) . Finally , more education predicted greater use of Web 2.0 for health information , with college graduates ( OR 2.57 , Wald= 3.86 , df = 1 , P=.049 ) and post graduates ( OR 7.105 , Wald= 4.278 , df=1 , P=.04 ) nearly 2 to 7 times more likely than non-high school graduates to use Web 2.0 for health information . Conclusions Being younger and possessing more education was associated with greater eHealth literacy among baby boomers and older adults . Females and those highly educated , particularly at the post graduate level , reported greater use of Web 2.0 for health information . More in-depth surveys and interviews among more diverse groups of baby boomers and older adult population s will likely yield a better underst and ing regarding how current Web-based health information seeking and sharing behaviors influence health-related decision making BACKGROUND Little research has examined adolescent health literacy and its relationship with online health information sources . The purpose of this study is to explore health literacy among a predominantly Hispanic adolescent population and to investigate whether exposure to a credible source of online health information , Medline Plus ( ® ) , is associated with higher levels of health literacy . METHODS An online survey was administered to a cross-sectional r and om sample of high school students in South Texas . Self-reported sociodemographic characteristics and data on health-information-seeking behavior and exposure to Medline Plus ( ® ) were collected . Health literacy was assessed by eHEALS and the Newest Vital Sign ( NVS ) . Linear and binary logistic regressions were completed . RESULTS Of the 261 students who completed the survey , 56 % had heard of Medline Plus ( ® ) , 52 % had adequate levels of health literacy as measured by NVS , and the mean eHEALS score was 30.6 ( possible range 8 - 40 ) . Health literacy was positively associated with self-efficacy and seeking health information online . Exposure to Medline Plus ( ® ) was associated with higher eHealth literacy scores ( p < .001 ) and increased the likelihood of having adequate health literacy ( odds ratio : 2.1 ; 95 % CI : 1.1 , 4.1 ) . CONCLUSION Exposure to a credible source of online health information is associated with higher levels of health literacy . The incorporation of a credible online health information re source into school health education curricula is a promising approach for promoting health literacy Background Reading skills are important for accessing health information , using health care services , managing one 's health and achieving desirable health outcomes . Our objective was to assess the diagnostic accuracy of the Single Item Literacy Screener ( SILS ) to identify limited reading ability , one component of health literacy , as measured by the S-TOFHLA . Methods Cross-sectional interview with 999 adults with diabetes residing in Vermont and bordering states . Participants were r and omly recruited from Primary Care practice s in the Vermont Diabetes Information System June 2003 – December 2004 . The main outcome was limited reading ability . The primary predictor was the SILS . Results Of the 999 persons screened , 169 ( 17 % ) had limited reading ability . The sensitivity of the SILS in detecting limited reading ability was 54 % [ 95 % CI : 47 % , 61 % ] and the specificity was 83 % [ 95 % CI : 81 % , 86 % ] with an area under the Receiver Operating Characteristics Curve ( ROC ) of 0.73 [ 95 % CI : 0.69 , 0.78 ] . Seven hundred seventy ( 77 % ) screened negative on the SILS and 692 of these subjects had adequate reading skills ( negative predictive value = 0.90 [ 95 % CI : 0.88 , 0.92 ] ) . Of the 229 who scored positive on the SILS , 92 had limited reading ability ( positive predictive value = 0.4 [ 95 % CI : 0.34 , 0.47 ] ) . Conclusion The SILS is a simple instrument design ed to identify patients with limited reading ability who need help reading health-related material s. The SILS performs moderately well at ruling out limited reading ability in adults and allows providers to target additional assessment of health literacy skills to those most in need . Further study of the use of the SILS in clinical setting s and with more diverse Output:	CONCLUSION Barriers to access to and use of online health information can result from the readability of content and poor usability of eHealth services . Mobile apps hold great potential for eHealth and mHealth services tailored to people with low health literacy .
MS22599	*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: Different food production methods may result in differences in the content of secondary metabolites such as polyphenolic compounds . The present study compared conventionally ( CPD ) and organically produced ( OPD ) diets in a human crossover intervention study ( n = 16 ) with respect to the intake and excretion of five selected flavonoids and effect on markers of oxidative defense . The urinary excretion of quercetin and kaempferol was higher after 22 days of intake of the OPD when compared to the CPD ( P < 0.05 ) . The excretions of flavonoids in urine as a percentage of intake ( 0.6 - 4 % ) were similar after both interventions . Most markers of antioxidative defense did not differ between the diets , but intake of OPD result ed in an increased protein oxidation and a decreased total plasma antioxidant capacity compared to baseline ( P < 0.05 ) . Some varietal difference was seen in the study , and because selection of more resistant varieties is of central importance to organic farming , it can not be excluded that the observed effects originate from these differences . The food production method affected the content of the major flavonoid , quercetin , in foods and also affected urinary flavonoids and markers of oxidation in humans Soy phytoestrogens were suggested to reduce the risk of a number of diseases including breast cancer . Given that these compounds are metabolized by bacteria , alteration of intestinal bacteria and enzymes may affect phytoestrogen metabolism . We hypothesized that probiotics , when consumed with soy protein , would increase plasma isoflavones , as well as equol producer frequency , in postmenopausal women . We further hypothesized that these effects would differ between women who have had breast cancer and women who have not . To test these hypotheses , 20 breast cancer survivors and 20 controls completed four 6-wk treatments in a r and omized , crossover design : supplementation with soy protein ( S ) ( 26.6 + /- 4.5 g protein , 44.4 + /- 7.5 mg isoflavones/d ) ; soy + probiotics ( S+P ) ( 10(9 ) colony-forming units Lactobacillus acidophilus DDS+1 and Bifidobacterium longum , 15 - 30 mg fructooligosaccharide/d ) ; milk protein ( M ) ( 26.6 + /- 4.5 g protein/d ) ; and milk + probiotics ( M+P ) . Plasma phytoestrogen concentrations did not differ between controls and survivors , although genistein tended to be lower in survivors at baseline ( P = 0.15 ) , and during soy ( P = 0.16 ) and milk protein ( P = 0.16 ) consumption . As expected , soy consumption increased plasma phytoestrogen concentrations ( P < 0.0001 ) . Plasma phytoestrogen concentrations and the number of equol producers did not differ between the S and S+P diets . At the same time , plasma equol concentrations as well as urinary equol excretion in 2 subjects were more than 7-fold different between the 2 diets . These results indicate that this particular probiotic supplement does not generally affect plasma isoflavones , although the large differences between plasma and urinary equol in some subjects suggest that equol producer status may be modifiable in some individuals Soybeans contain isoflavones , which have been associated with many health benefits , including decreased cancer risk . The purpose of our study was to measure urinary isoflavonoid excretion in response to daily consumption of soy that contained 0 - 36 mg isoflavones -- a lower range than used in previous studies -- and to compare urinary isoflavonoid excretion between equol excreters and nonexcreters . Fourteen men and women aged 20 - 40 y participated in the study . Half of the subjects were identified previously as equol excreters and the other half as equol nonexcreters . This r and omized , double-blind , crossover study consisted of four 9-d diet treatment periods . During each treatment period participants consumed a low-photoestrogen controlled diet and a beverage containing 0 , 5 , 10 , or 20 g soy protein . Urine collected on the last 3 d of each treatment period was analyzed for isoflavonoid ( equol , O-desmethylangolensin , genistein , and daidzein ) and lignan ( enterodiol and enterolactone ) contents by using isotope-dilution gas chromatography-mass spectrometry . There was a highly linear dose response of urinary isoflavonoid excretion to soy consumption , which did not differ significantly between equol excreters and nonexcreters . There were no significant differences in lignan excretion between the two diet treatments . Our results indicate that urinary isoflavonoid excretion is dose dependent in humans at low to moderate levels of soy consumption We investigated whether the bioavailability of isoflavones could be enhanced by enzymatic hydrolysis of glycosides to aglycones before consumption of a nonfermented soy food . Two drinks were formulated with an enriched isoflavone extract from soy germ ( Fujiflavone P10 ) , one of which was hydrolyzed enzymatically with beta-glucosidase to produce aglycones . In a r and omized , double-blinded , cross-over study , six European , postmenopausal women consumed each soy drink at a 1-wk interval at a concentration of 1 mg total isoflavones/kg body . The plasma and urinary pharmacokinetics of daidzein , genistein and glycitein did not differ after consumption of the two beverages . Plasma total isoflavone concentrations reached 4 - 5 micro mol/L. The pharmacokinetics of glycitein were similar to those of daidzein . The isoflavone secondary metabolites detected were dihydrodaidzein in plasma and O-desmethylangolensin , equol , and dihydrogenistein in urine . The ratios of individual isoflavones to one another were not conserved from food to plasma to urine , indicating that the individual isoflavones do not have the same absorptions and body retentions . In conclusion , previous hydrolysis of glycosides to aglycones does not enhance the bioavailability of isoflavones in humans BACKGROUND Test results on the bioavailability of isoflavones in the aglycone or glucoside form in Eastern and Western human subjects are contradictory . OBJECTIVE The objective was to investigate the bioavailability of the soy isoflavones daidzein and genistein in American women with typical American dietary habits after ingestion of the aglycone or glucoside form of isoflavones . DESIGN Fifteen American women aged 46 + /- 6 y participated in a r and omized , double-blind study . Blood sample s were collected 0 , 1 , 2 , 4 , 8 , 12 , 24 , and 48 h after consumption of aglycone or glucoside tablets with breakfast . The plasma curves for daidzein , genistein , and equol were constructed and the postpr and ial maximum concentration ( C(max ) ) , time to the maximum concentration ( t(max ) ) , and area under the curve ( AUC ) were determined . RESULTS Isoflavone concentrations peaked early ( 1 - 2 h ) in plasma and peaked again at 4 - 8 h. Mean C(max ) , t(max ) , and AUC values for genistein were not significantly different after ingestion of aglycone or glucoside . However , C(max ) and AUC values , but not t(max ) , were significantly higher for daidzein after aglycone ingestion , which was partly due to its higher content in the aglycone tablets . Equol appeared after 4 h and remained elevated after 48 h. Despite a higher content of daidzein in the aglycone tablets , the AUC for equol was significantly higher after ingestion of the glucoside tablets , probably because of the metabolic action of intestinal bacteria during the long intestinal transit time of glucoside . CONCLUSION The apparent bioavailability of genistein and daidzein is not different when consumed as either aglycone or glucoside by American women BACKGROUND Soy isoflavones are potential cancer chemoprevention treatments . OBJECTIVE We conducted safety studies of purified unconjugated genistein , daidzein , and glycitein , and defined pharmacokinetic parameters for their absorption and metabolism . DESIGN Thirty healthy men ingested a single dose of 1 of 2 isoflavone preparations purified from soy . The delivered doses of genistein ( 1 , 2 , 4 , 8 , or 16 mg/kg body wt ) were higher than those previously administered to humans . Formulation A was composed of 90 + /- 5 % genistein , 10 % daidzein , and 1 % glycitein . Formulation B was composed of 43 % genistein , 21 % daidzein , and 2 % glycitein . RESULTS We observed no clinical ly significant behavioral or physical changes after treatment . We observed elevations in lipoprotein lipase and hypophosphatemia that were possibly related to the treatment but that were associated with no clinical toxicity . Considerable quantities of isoflavones were excreted in urine as conjugates . The terminal elimination rate , elimination half-life , area under the curve , maximum plasma concentration , apparent systemic clearance , and volume of distribution were estimated for genistein and daidzein . The mean elimination half-lives with both formulations were 3.2 h for free genistein and 4.2 h for free daidzein . The mean pseudo half-lives were 9.2 h for total genistein and 8.2 h for total daidzein . CONCLUSIONS Dietary supplements of purified unconjugated isoflavones administered to humans in single doses exceeding normal dietary intake manyfold result ed in minimal clinical toxicity . Genistein and daidzein ( free and total ) were rapidly cleared from plasma and excreted in urine We examined the associations of intake of vegetables , legumes and fruit with all-cause and cause-specific mortality in a population with prevalent diabetes in Europe . A cohort of 10,449 participants with self-reported diabetes within the European Prospect i ve Investigation into Cancer and Nutrition study was followed for a mean of 9 y. Intakes of vegetables , legumes , and fruit were assessed at baseline between 1992 and 2000 using vali date d country-specific question naires . A total of 1346 deaths occurred . Multivariate relative risks ( RR ) for all-cause mortality were estimated in Cox regression models and RR for cause-specific mortality were derived in a competing risk model . An increment in intake of total vegetables , legumes , and fruit of 80 g/d was associated with a RR of death from all causes of 0.94 [ 95 % CI 0.90 - 0.98 ] . Analyzed separately , vegetables and legumes were associated with a significantly reduced risk , whereas nonsignificant inverse associations for fruit intake were observed . Cardiovascular disease ( CVD ) mortality and mortality due to non-CVD/non-cancer causes were significantly inversely associated with intake of total vegetables , legumes , and fruit ( RR 0.88 [ 95 % CI 0.81 - 0.95 ] and 0.90 [ 0.82 - 0.99 ] , respectively ) but not cancer mortality ( 1.08 [ 0.99 - 1.17 ] ) . Intake of vegetables , legumes , and fruit was associated with reduced risks of all-cause and CVD mortality in a diabetic population . The findings support the current state of evidence from general population studies that the protective potential of vegetable and fruit intake is larger for CVD than for cancer and suggest that diabetes patients may benefit from a diet high in vegetables and fruits Flavonols are antioxidants that may reduce the risk of heart disease . Two major flavonols in the diet are quercetin and kaempferol , and their main sources in The Netherl and s are tea and onions . We investigated whether plasma concentrations and urinary excretion of quercetin and kaempferol in humans could be used as biomarkers of intake . We provided 15 subjects with strong black tea ( 1600 mL/d ) or fried onions ( 129 g/d ) for 3 d each in r and om order separated by a 4-d washout period . The tea provided 49 mg quercetin and 27 mg kaempferol daily and the onions provided 13 mg quercetin and no kaempferol . Flavonols from both foods were clearly absorbed . However , the excretion of unmodified quercetin was 0.5 % of intake after tea and 1.1 % after onions . Thus , the absorption of quercetin from tea was half of that from onions . The onion treatment was repeated 7 - 14 d later to estimate within-subject CVs as a measure of reproducibility when the same treatment is given twice . CVs for quercetin were 30 % in plasma and 42 % in urine . The magnitude of these variations relative to actual variations of approximately 60 % between free-living subjects indicates that concentrations of quercetin in plasma and urine are applicable as biomarkers of its intake . We conclude that flavonols in plasma and urine reflect short-term flavonol intake and that they could be used as biomarkers to distinguish between high and low flavonol consumption in epidemiologic studies The effects of consuming a soy protein isolate beverage powder ( 60 g/d for Output:	Both genistein and daidzein exhibited dose-response relationships . Other isoflavonoid levels such as O-desmethylangolensin ( O-DMA ) and equol were also reported to increase following soy consumption . Using a developed scoring system , genistein and daidzein can be considered as promising c and i date markers for soy consumption . Furthermore , genistein and daidzein also served as good estimates of soy intake as evidence d from long-term exposure studies marking their status as vali date d biomarkers . On the contrary , only few studies indicated proposed biomarkers for pulses intake , with pipecolic acid and S-methylcysteine reported as markers reflecting dry bean consumption , unsaturated aliphatic , hydroxyl-dicarboxylic acid related to green beans intake and trigonelline reported as marker of peas consumption .

Subsets and Splits

No community queries yet

The top public SQL queries from the community will appear here once available.