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MS21900	*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 Pediatric r and omized controlled trials ( RCTs ) are susceptible to a high risk of bias . We examined the barriers and facilitators that pediatric trialists face in the design and conduct of unbiased trials . Methods We used a mixed methods design , with semi-structured interviews building upon the results of a quantitative survey . We surveyed Canadian ( n=253 ) and international ( n=600 ) pediatric trialists regarding their knowledge and awareness of bias and their perceived barriers and facilitators in conducting clinical trials . We then interviewed 13 participants from different subspecialties and geographic locations to gain a more detailed description of how their experiences and attitudes towards research interacted with trial design and conduct . Results The survey response rate was 23.0 % ( 186/807 ) . 68.1 % of respondents agreed that bias is a problem in pediatric RCTs and 72.0 % felt that there is sufficient evidence to support changing some aspects of how trials are conducted . Knowledge related to bias was variable , with inconsistent awareness of study design features that may introduce bias into a study . Interview participants highlighted a lack of formal training in research methods , a negative research culture , and the pragmatics of trial conduct as barriers . Facilitators included contact with knowledgeable and supportive colleagues and infrastructure for research . Conclusions A lack of awareness of bias and negative attitudes towards research present significant barriers in terms of conducting method ologically rigorous pediatric RCTs . Knowledge translation efforts must focus on these issues to ensure the relevance and validity of trial results Background : Administration of bupivacaine caudally has been used for postoperative analgesia after urogenital , rectal and lower abdominal surgery in children . Caudal opioids may offer analgesic advantages over bupivacaine alone but have been associated with side effects such as respiratory depression . Tramadol is an analgesic assumed to lack a respiratory depressant effect and has been shown to provide effective , long‐lasting analgesia after epidural administration in adults and children . The aim of this study was to determine whether the addition of tramadol to bupivacaine caudally prolongs the duration of analgesia compared with bupivacaine alone , with respect to side effects , and whether caudal tramadol alone provides satisfactory analgesia OBJECT Stable hemodynamics , normocapnia , and adequate pain relief are considered important factors in the reduction of neurological complications in pediatric patients undergoing encephaloduroarteriomyosynangiosis ( EDAMS ) operations for the treatment of moyamoya disease . A preoperative skull block may reduce hemodynamic fluctuations and hypo- or hyperventilation due to emergence delirium or oversedation and provide adequate pain relief , thereby reducing postoperative morbidity . METHODS Pediatric patients ( age 3 - 13 years ) undergoing EDAMS surgery for moyamoya disease were r and omly divided into a nerve block ( NB ) group ( 18 cases ) or control group ( 21 cases ) . The treatment group patients received a preoperative NB ( 0.25 % 5 - 8 ml bupivacaine mixed with 20 - 40 mg methylprednisolone ) targeting the supraorbital , supratrochlear , auriculotemporal , and posterior auricular nerves . Patients in the control group did not receive NB . General anesthesia with sevoflurane was induced in both groups . RESULTS In the NB group , stable hemodynamic parameters were obtained with a lower sevoflurane concentration than in the control group . For delirious awakening , the odds ratio in the control group was 4.9 compared with the NB group . Pain and analgesic requirement were higher in the control patients than in the NB-treated patients during the postanesthesia care unit stay . However , the arterial CO(2 ) tension in the postanesthesia care unit did not differ between the 2 groups . The odds ratio in the control group for the rate of morbidity ( cerebral infa rct ion and reversible ischemic neurological deficits ) during the first 24 hours following the operation was 3.2 compared with the NB group . CONCLUSIONS The use of skull block during EDAMS surgery provided easy hemodynamic control , calm awakening , and better pain relief and may be related to the reduced postoperative morbidity BACKGROUND : The classical response to nerve stimulation may be altered in cases of radial club h and . Ultrasound guidance may prove to be a useful tool in such situations . In this study , we compared the success rate of ultrasound-guided infraclavicular brachial plexus block with nerve stimulation for children undergoing radial club h and repair . METHODS : Fifty children , aged 1 - 2 yr , undergoing radial club h and repair were r and omly assigned to receive infraclavicular brachial plexus block guided by nerve stimulator ( Group NS ) or ultrasound ( Group U ) in combination with light general anesthetic . Bupivacaine 0.5 mL/kg of 0.5 % was injected in both groups . Pain response to surgical stimulus was considered as block failure . The Children ’s Hospital Eastern Ontario Pain Scale pain score was recorded at 1 , 4 , 6 , 8 , and 10 postoperative hours . RESULTS : In Group NS , the blocks were successful in 16 of 25 patients ( 64 % ) , whereas in Group U , 24 of 25 patients had successful blocks ( P = 0.0053 ) . There was no difference in the time to first analgesia or analgesic consumption in the 10-h study period . CONCLUSION : Ultrasound-guided infraclavicular brachial plexus block improves the success rate in patients with radial club h and s when compared with nerve stimulation in patients undergoing radial club h and correction We compared in a r and omized double-blind study , the postoperative analgesia and degree of motor block produced by the new local anaesthetic ropivacaine , with bupivacaine , for caudal anaesthesia in children . Eighty children , 2 - 5-years-old , ASA I , received one of two local anaesthetics ; either ropivacaine 0.25 % ( 1.0 ml x kg(-1 ) ) or bupivacaine 0.25 % ( 1.0 ml x kg(-1 ) ) . They were se date d with a continuous infusion of propofol ( 200 microg x kg(-1 ) min(-1 ) . The lungs were ventilated with a mixture of 50 % nitrous oxide with oxygen . 60 min after local anaesthetic injection , and every 60 min , the extent of the motor block in the recovery room was scored as 1 - 3 , according to a modified Bromage scale . Adverse events and the time to the first analgesic requirement were reported . Patients in the two groups did not differ with respect to age , weight and height . There were no differences in heart rate and arterial pressure between the two groups(P>0.05 ) . No adverse events were observed . The ropivacaine group showed a shorter duration of motor block than the bupivacaine group ( P<0.05 ) . The first postoperative analgesic requirement was a mean ( sd ) of 5 h+/-4.32 after the operation in the ropivacaine group and 5 h+/-3.81 for the bupivacaine group . These findings suggest that caudal anaesthesia with ropivacaine 0.25 % in paediatric patients can be effective , with less motor blockade in the postoperative period OBJECTIVE We set out to compare a eutectic mixture of local anesthetic cream ( lidocaine and prilocaine ) to dorsal penile nerve block with lidocaine for anesthesia during circumcision . STUDY DESIGN In a double-blind study , term newborns were r and omized to local anesthetic cream and sodium chloride solution dorsal penile nerve block ( n = 31 ) or to placebo cream and lidocaine dorsal penile nerve block ( n = 29 ) . Pain was assessed by determination of heart rate , respiratory rate , and behavioral distress scoring . Group differences were evaluated with repeat- measures analyses of variance . RESULTS Distress scores and heart rates were significantly higher in the eutectic mixture group than in the lidocaine group . Respiratory rates were higher in the eutectic mixture group but did not reach statistical significance . CONCLUSIONS Distress scores and heart rates were significantly higher in infants treated with the anesthetic mixture than in infants treated with lidocaine . Dorsal penile nerve block with lidocaine is a more efficacious means of providing anesthesia for neonatal circumcision than the mixture of local anesthetics BACKGROUND We attempted to determine the efficacy of a one plane ilioinguinal and iliohypogastric nerve block with a single shot and double shot techniques . METHODS In a r and omized single blind study , 90 children , aged 2 - 12 years , received a single shot ( SS ) or a double shot ( DS ) technique for ilioinguinal and iliohypogastric ( IG-IH ) nerve block for inguinal hernia repair . In the SS group , 0.25 ml x kg(-1 ) of 0.25 % bupivacaine was given one fingerbreadth medial to the anterior superior iliac spine under the external oblique aponeurosis . In the DS group , one-third of the total dose of bupivacaine was given as for the SS group . The remaining two-thirds was deposited 0.5 cm above and lateral to the mid-inguinal point deep to the external oblique aponeurosis . RESULTS The success rates of both techniques were similar , at 72 % , although the presence of local anaesthetic in the inguinal canal was significantly higher with the DS technique . The incidence of femoral nerve block was 4.5 % with the SS and 9 % with the DS technique ( P > 0.05 ) . Parental satisfaction with postoperative pain relief was high , at 94 % . CONCLUSIONS The DS technique , while technically more difficult , does not improve the success rate of the IG-IH nerve block compared with the SS technique BACKGROUND Dorsal penile nerve block ( DPNB ) is a commonly performed regional anesthetic technique for male circumcision . Traditionally , DPNB is based on an anatomical l and mark technique . Recently , an ultrasound-guided technique for DPNB has been described . OBJECTIVES The aim of our study was to compare the anatomical l and mark technique with this ultrasound-guided technique . The hypothesis to be tested was that ultrasound guidance of DPNB would lead to less administration of opioid when compared to the anatomical l and mark technique . METHODS Boys of ASA status I/II scheduled for day case circumcision were prospect ively recruited and r and omized . DPNB was performed under general anesthesia using the anatomical l and mark technique or ultrasound guidance . Fentanyl was administered intraoperatively and immediately postoperatively if patients demonstrated signs of pain . Similarly , oral codeine was given prior to discharge if required . The primary outcome measure was the number of patients requiring fentanyl . Secondary outcome measures included initial pain score on emergence from general anesthesia , requirement for codeine predischarge , and time to perform block . RESULTS A total of 32 patients were recruited to the l and mark group and 34 to the ultrasound group . There was no significant difference between the two groups in terms of fentanyl administration . The ultrasound technique took longer to perform but was associated with a reduction in codeine requirement prior to discharge . CONCLUSIONS This study does not support the routine use of ultrasound for the performance of DPNB in male pediatric circumcision . Nonetheless , an associated reduction in codeine administration postoperatively suggests some benefit in terms of postoperative pain We compared the effects of pre- and postsurgical axillary block on pain after h and and forearm surgery in 55 children in a double-blind r and omized study . The successful blocks are reported here ( n=49 ) . Children aged 1 - 11 years and ASA I or II were allocated r and omly to receive axillary block with 2 mg.kg-1 of 0.25 % bupivacaine , either after induction but before the surgery ( presurgical group , n=25 ) or immediately after surgery , before the end of anaesthesia ( postsurgical , n=24 ) . In all patients , a st and ard general anaesthesia technique was used . The Faces Pain Scale ( FPS ) and analgesic requirements were recorded for 24 h at various times after operation . Eight patients ( 32 % ) in the presurgical group and 20 patients ( 83.33 % ) in the postsurgical group did not require additional analgesic within the first 24 h after operation ( P < 0.05 ) . In patients who had pain during the observation period , the pain started 13.66+/-2.61 h in the presurgical group and 13.14+/-2.34 h in the postsurgical group after performing block ( P > 0.05 ) . The FPS scores were similar in both groups during the first 8 h in the postoperative period ( P > 0.05 ) . There was a significant difference at 10 h after surgery ( P < 0.05 ) . Cumulative FPS score was higher in the presurgical group ( 10.50+/-1.06 ) than in the postsurgical group ( 9.45+/-1.28 ) ( P < 0.05 ) , but both groups had effective analgesia overall , the mean FPS score being less than 2 . Additional analgesic consumption was similar in these patients in both groups . A lower isoflurane concentration was used in the presurgical group ( 0.68 % vs 1.72 % , P < 0.001 ) . We Output:	Additional evidence is required to support the use of specific regional anaesthesia techniques to improve postoperative pain for several surgical procedures ( craniectomy , adenotonsillectomy , appendectomy , cardiac surgery , umbilical hernia repair , upper and lower extremity ) in paediatric patients . Currently , only a very limited number of regional anaesthesia techniques have demonstrated significant improvement on postoperative pain outcomes for a restricted number of surgical procedures .
MS21901	*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 Purpose We aim ed to evaluate early response to two different corticosteroids doses after Kasai portoenterostomy for biliary atresia ( BA ) . Methods A prospect i ve , r and omized trial was performed in infants from the nationwide BA registry with type 3 BA . Sixty-nine infants were r and omized to receive either 4 mg/kg/day ( group A , n = 35 ) or 2 mg/kg/day prednisolone ( group B , n = 34 ) . The corticosteroids were started on postoperative day 7 , and the dose was tapered toward day 30 . Results of liver function tests on days 31 and 60 were compared between the groups . Results Mean bilirubin , AST , ALT , and GGT levels did not significantly differ between the groups . However , the levels of total and direct bilirubin of infants < 70 days old at surgery significantly differed between the groups . Four patients from group A and five from group B , dropped out of the study . Complications during the first month after PE were comparable between the groups . Conclusions An initial 4 mg/kg/day dose did not significantly improve liver function , except that bilirubin levels were lower in the subgroup of infants < 70 days old at surgery . There were no significant complications with either dose of corticosteroids Objective : To identify the epidemiological characteristics of infants with biliary atresia in Engl and and Wales , since central isation of its management in 1999 . Methods : The care of infants with biliary atresia ( BA ) in Engl and and Wales is central ised to only three centres . All infants ( treated from January 1999 to December 2006 ) were identified from a prospect i ve national data base ; demographic details were ascertained from medical records and compared between two groups based on presumed aetiology ( isolated biliary atresia ( IBA ) and developmental biliary atresia ( DBA ) ( for example , syndromic infants , biliary atresia splenic malformation , cystic biliary atresia ) ) . Results : There were 302 ( 133 male ( 44 % ) ) infants with BA that could be divided into IBA ( n = 219 , 73 % ) and DBA ( n = 76 , 25 % ) . The overall incidence was 0.58/10 000 ( 1 in 17 049 ) live births with marked regional differences along a north-west/south-east axis varying from 0.38 ( north-west Engl and ) to 0.78 ( south-east Engl and ) /10 000 live births ( OR 2.05 ( 95 % CI 1.26–3.41 ) ; p = 0.002 ) . The commonest month of birth was September with December being the least common , although there was no evidence for significant seasonal variation ( p = 0.2 ) . Infants with DBA were more likely to be female ( p<0.001 ) , of white background ( p = 0.01 ) , first-born ( p = 0.04 ) and to be formula-fed ( p = 0.07 ) . Infants of south Asian origin came to surgery at an older age ( 59 ( IQ 45–75 ) versus 52 ( IQ 42–65 ) days ; p = 0.03 ) . Conclusions : There is a remarkable variation of incidence of biliary atresia within Engl and and Wales , some of which may have been caused by factors related to a different aetiological and racial background OBJECTIVE : Postoperative adjuvant steroid treatment is reported to improve jaundice-free survival in biliary atresia ( BA ) patients and to reduce the need for early liver transplantation . However , evidence of all retrospective studies is very limited , although high-dose corticosteroids were favored . The aim of this dosage finding study was to test the most promising corticosteroid protocol in a smaller but representative series , in order to optimize the setting s of upcoming prospect i ve and long-term multicenter studies . METHODS : Our prospect i ve single-center and open-labeled pilot study on high-dose steroids included 49 consecutive BA patients . Basic data of the study group were not different from 29 controls . In the study group , 20 consecutive patients were treated after the Kasai with methylprednisolone ( 10 mg/kg day 1 to 5 and 1 mg/kg day 6 to 28 ) . RESULTS : Overall survival with native liver was 63 % after 6 months and 31 % after 2 yr , with no statistical difference between the study and control groups . After 2 yr , 27 % of all patients were still jaundice-free . With regard to predictive parameters , we found , 6 months after the Kasai , bilirubin < 20 μmol/L as highly sensitive ( 97 % ) and specific ( 93 % ) for jaundice-free survival with native liver . CONCLUSIONS : In contrast to previous reports , this pilot study shows that high-dose steroid pulses after Kasai procedure are not effective in postoperative adjuvant therapy protocol s and should be avoided in upcoming multicenter steroid studies . Therefore , we recommend extended and r and omized multicenter studies to pre-evaluate the supposed effectiveness of alternative steroid protocol s , by comparing , 6 months after the Kasai procedure , the number of patients with normal bilirubin BACKGROUND AND AIMS Perinatal cytomegalovirus ( CMV ) infection is a possible cause or trigger of biliary atresia though clinical evidence is scant . We hypothesised that CMV IgM+ve biliary atresia is a separate clinical entity compared to CMV IgM-ve biliary atresia . METHODS Prospect i ve single-centre study . 210 infants with histologically confirmed biliary atresia were treated in our institution ( Jan. 2004 to Dec. 2011 ) ; of these 20 ( 9.5 % ) were CMV IgM+ve at presentation . We compared these with 111 infants who were CMV IgM-ve ( controls ) for clinical features , biochemistry at presentation and outcome following Kasai portoenterostomy ( KPE ) . A blinded comparison of age-matched liver histology was also performed . Data are quoted as median ( interquartile range ) . A P value ≤ 0.05 was regarded as significant . RESULTS Infants with CMV IgM+ve biliary atresia were older at Kasai portoenterostomy ( or laparotomy ) [ 70 ( 60 - 80 ) days vs. 56 (44 - 75)days ; P = 0.003 ] and were more jaundiced [ 175 ( 147 - 224 ) vs. 140 ( 121 - 181 ) μmol/L ; P = 0.002 + with higher AST*287 ( 157 - 403 ) vs. 180 ( 133 - 254 ) IU/L ; P = 0.005 ] and aspartate aminotransferase-to-platelet ratio index [ 1.1 ( 0.79 - 3.0 ) vs. 0.63 ( 0.43 - 0.95 ) ] levels . Liver histology : CMV IgM+ve biliary atresia was characterised by a greater degree of inflammation ( P < 0.0001 ) and fibrosis ( P = 0.02 ) , whereas CMV IgM-ve isolated biliary atresia had a higher degree of lobular cholestasis ( P = 0.001 ) . This effect was independent of the effects of age at KPE . OUTCOME CMV IgM+ve biliary atresia had a poorer outcome with a reduced clearance of jaundice ( 15 % vs. 52.2 % ; P = 0.002 ) , native liver survival ( P < 0.0001 ) and increased mortality ( P = 0.002 ) . CONCLUSIONS CMV IgM+ve biliary atresia is a distinct clinical and pathological entity with a diminished response to Kasai portoenterostomy IMPORTANCE Biliary atresia is the most common cause of end-stage liver disease in children . Controversy exists as to whether use of steroids after hepatoportoenterostomy improves clinical outcome . OBJECTIVE To determine whether the addition of high-dose corticosteroids after hepatoportoenterostomy is superior to surgery alone in improving biliary drainage and survival with the native liver . DESIGN , SETTING , AND PATIENTS The multicenter , double-blind Steroids in Biliary Atresia R and omized Trial ( START ) was conducted in 140 infants ( mean age , 2.3 months ) between September 2005 and February 2011 in the United States ; follow-up ended in January 2013 . INTERVENTIONS Participants were r and omized to receive intravenous methylprednisolone ( 4 mg/kg/d for 2 weeks ) and oral prednisolone ( 2 mg/kg/d for 2 weeks ) followed by a tapering protocol for 9 weeks ( n = 70 ) or placebo ( n = 70 ) initiated within 72 hours of hepatoportoenterostomy . MAIN OUTCOMES AND MEASURES The primary end point ( powered to detect a 25 % absolute treatment difference ) was the percentage of participants with a serum total bilirubin level of less than 1.5 mg/dL with his/her native liver at 6 months posthepatoportoenterostomy . Secondary outcomes included survival with native liver at 24 months of age and serious adverse events . RESULTS The proportion of participants with improved bile drainage was not statistically significantly improved by steroids at 6 months posthepatoportoenterostomy ( 58.6 % [ 41/70 ] of steroids group vs 48.6 % [ 34/70 ] of placebo group ; adjusted relative risk , 1.14 [ 95 % CI , 0.83 to 1.57 ] ; P = .43 ) . The adjusted absolute risk difference was 8.7 % ( 95 % CI , -10.4 % to 27.7 % ) . Transplant-free survival was 58.7 % in the steroids group vs 59.4 % in the placebo group ( adjusted hazard ratio , 1.0 [ 95 % CI , 0.6 to 1.8 ] ; P = .99 ) at 24 months of age . The percentage of participants with serious adverse events was 81.4 % [ 57/70 ] of the steroids group and 80.0 % [ 56/70 ] of the placebo group ( P > .99 ) ; however , participants receiving steroids had an earlier time of onset of their first serious adverse event by 30 days posthepatoportoenterostomy ( 37.2 % [ 95 % CI , 26.9 % to 50.0 % ] of steroids group vs 19.0 % [ 95 % CI , 11.5 % to 30.4 % ] of placebo group ; P = .008 ) . CONCLUSIONS AND RELEVANCE Among infants with biliary atresia who have undergone hepatoportoenterostomy , high-dose steroid therapy following surgery did not result in statistically significant treatment differences in bile drainage at 6 months , although a small clinical benefit could not be excluded . Steroid treatment was associated with earlier onset of serious adverse events in children with biliary atresia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00294684 BACKGROUND We studied the outcomes at school age in children who had participated in a double-blind , placebo-controlled trial of early postnatal dexamethasone therapy ( initiated within 12 hours after birth ) for the prevention of chronic lung disease of prematurity . METHODS Of the 262 children included in the initial study , 159 lived to school age . Of these children , 146 ( 72 in the dexamethasone group and 74 in the control group ) were included in our study . All the infants had had severe respiratory distress syndrome requiring mechanical ventilation shortly after birth . In the dexamethasone group , 0.25 mg of dexamethasone per kilogram of body weight was given intravenously every 12 hours for one week , and then the dose was tapered . We evaluated the children 's growth , neurologic and motor function , cognition , and school performance . RESULTS Children in the dexamethasone group were significantly shorter than the controls ( P=0.03 for boys , P=0.01 for girls , and P=0.03 for all children ) and had a significantly smaller head circumference ( P=0.04 ) . Children in the dexamethasone group had significantly poorer motor skills ( P<0.001 ) , motor coordination ( P<0.001 ) , and visual-motor integration ( P=0.02 ) . As compared with the controls , children in the dexamethasone group also had significantly lower full IQ scores ( mean [ + /-SD ] , 78.2+/-15.0 vs. 84.4+/-12.6 ; P=0.008 ) , verbal IQ scores ( 84.1+/-13.2 vs. 88.4+/-11.8 , P=0.04 ) , and performance IQ scores ( 76.5+/-14.6 vs. 84.5+/-12.7 , P=0. Output:	Clearance of jaundice is related to the age at KPE in infants who receive high-dose steroids . Native liver survival appears to be improved as a result of this . This is the first study to show tangible longer-term benefit from high-dose steroids in biliary atresia
MS21902	*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: R and omised controlled trials have shown that the policy of mammographic screening confers a substantial and significant reduction in breast cancer mortality . This has often been accompanied , however , by an increase in breast cancer incidence , particularly during the early years of a screening programme , which has led to concerns about overdiagnosis , that is to say , the diagnosis of disease that , if left undetected and therefore untreated , would not become symptomatic . We used incidence data from two r and omised controlled trials of mammographic screening , the Swedish Two-county Trial and the Gothenburg Trial , to establish the timing and magnitude of any excess incidence of invasive disease and ductal carcinoma in situ ( DCIS ) in the study groups , to ascertain whether the excess incidence of DCIS reported early in a screening trial is balanced by a later deficit in invasive disease and provide explicit estimates of the rate of ' real ' and non-progressive ' overdiagnosed ' tumours from the study groups of the trials . We used a multistate model for overdiagnosis and used Markov Chain Monte Carlo methods to estimate the parameters . After taking into account the effect of lead time , we estimated that less than 5 % of cases diagnosed at prevalence screen and less than 1 % of cases diagnosed at incidence screens are being overdiagnosed . Overall , we estimate overdiagnosis to be around 1 % of all cases diagnosed in screened population s. These estimates are , however , subject to considerable uncertainty . Our results suggest that overdiagnosis in mammography screening is a minor phenomenon , but further studies with very large numbers are required for more precise estimation Background : The benefits and harms of population -wide mammography screening have been long debated . This study evaluated the impact of screening frequency and age range on breast cancer mortality reduction and overdiagnosis . Methods : We developed a Markov simulation model for the evaluation of mammography screening in a cohort of British women born in 1935–40 . Results : For triennial screening in women aged 47–73 , breast cancer mortality reduction and overdiagnosis was 18.1 % ( 95 % confidence interval : 17.3 % , 19.0 % ) and 5.6 % ( 5.1 % , 6.1 % ) , of all breast cancer deaths and diagnoses , respectively , from age 40 to 85 years . For annual screening in the same age range , estimates for both outcomes increased considerably to 35.0 % ( 34.2 % , 35.7 % ) and 7.6 % ( 7.1 % , 8.1 % ) , respectively . For the age extension of triennial screening from 50–70 to 47–73 , we estimated 5 ( 3 , 7 ) incremental breast cancer deaths avoided and 14 ( 9 , 19 ) incremental cases overdiagnosed per 10 000 women invited for screening . Conclusions : Estimates of mortality reduction and overdiagnosis were highly dependent on screening frequency , age range , and uptake , which may explain differences between some previous estimates obtained from r and omised trials and from service screening IMPORTANCE False-positive mammograms , a common occurrence in breast cancer screening programs , represent a potential screening harm that is currently being evaluated by the US Preventive Services Task Force . OBJECTIVE To measure the effect of false-positive mammograms on quality of life by measuring personal anxiety , health utility , and attitudes toward future screening . DESIGN , SETTING , AND PARTICIPANTS The Digital Mammographic Imaging Screening Trial ( DMIST ) quality -of-life sub study telephone survey was performed shortly after screening and 1 year later at 22 DMIST sites and included r and omly selected DMIST participants with positive and negative mammograms . EXPOSURE Mammogram requiring follow-up testing or referral without a cancer diagnosis . MAIN OUTCOMES AND MEASURES The 6- question short form of the Spielberger State-Trait Anxiety Inventory state scale ( STAI-6 ) and the EuroQol EQ-5D instrument with US scoring . Attitudes toward future screening as measured by women 's self-report of future intention to undergo mammographic screening and willingness to travel and stay overnight to undergo a hypothetical new type of mammography that would identify as many cancers with half the false-positive results . RESULTS Among 1450 eligible women invited to participate , 1226 ( 84.6 % ) were enrolled , with follow-up interviews obtained in 1028 ( 83.8 % ) . Anxiety was significantly higher for women with false-positive mammograms ( STAI-6 , 35.2 vs 32.7 ) , but health utility scores did not differ and there were no significant differences between groups at 1 year . Future screening intentions differed by group ( 25.7 % vs 14.2 % more likely in false-positive vs negative groups ) ; willingness to travel and stay overnight did not ( 9.9 % vs 10.5 % in false-positive vs negative groups ) . Future screening intention was significantly increased among women with false-positive mammograms ( odds ratio , 2.12 ; 95 % CI , 1.54 - 2.93 ) , younger age ( 2.78 ; 1.5 - 5.0 ) , and poorer health ( 1.63 ; 1.09 - 2.43 ) . Women 's anticipated high-level anxiety regarding future false-positive mammograms was associated with willingness to travel overnight ( odds ratio , 1.94 ; 95 % CI , 1.28 - 2.95 ) . CONCLUSIONS AND RELEVANCE False-positive mammograms were associated with increased short-term anxiety but not long-term anxiety , and there was no measurable health utility decrement . False-positive mammograms increased women 's intention to undergo future breast cancer screening and did not increase their stated willingness to travel to avoid a false-positive result . Our finding of time-limited harm after false-positive screening mammograms is relevant for clinicians who counsel women on mammographic screening and for screening guideline development groups Objective - To examine the psychological consequences at a number of stages in the screening process for women attending a screening mammography programme . Setting - A pilot mammographic screening programme in Melbourne , Australia . Method — The psychological consequences question naire ( PCQ ; a reliable and valid measure of the psychological consequences of screening mammography ) was used to measure the emotional , social , and physical functioning of women in a mammographic screening programme and a control community sample . A screening group ( in whom no abnormality was detected at initial screen ; n=142 ) had four measurements : at screening clinic ; before results were received ; one week after all-clear results were received ; and eight months after initial visit . The recall group ( who were recalled for further investigation which showed the detected abnormality to be benign ; n = 58 ) had measurements at the same points as the screening group and an additional measurement while waiting at the recall assessment clinic . A r and omly selected community control group ( n = 52 ) had measurements one week , two weeks , three weeks ; and eight months after consenting to participate . Results - Emotional , social , and physical functioning of women in the screening group did not change over time and at no point differed significantly from that of community controls . The profiles of emotional and physical dysfunction of women in the recall group differed significantly from those of the screening and control groups . The level of emotional and physical dysfunction in the recall group was highest while waiting at recall assessment clinic , and scores were still significantly higher than scores obtained at comparable times from screening and control groups one week after obtaining notification that there was no sign of cancer ( emotional P < 0·001 ; physical P < 0·05 ) . This difference had disappeared eight months after the screening visit , when the level of emotional and physical functioning was similar to that of the screening and control groups . Social dysfunction scores did not change significantly over time and were similar for all three groups . Conclusions - Given that up to 10 % of women are recalled for further investigations on first round screening , significant numbers of women may have psychological consequences . This speaks for the necessity for accurate reading of mammograms to minimise the false positive recall rate , and for counselling services to be available at recall assessment centres Objective To compare breast cancer incidence and mortality up to 25 years in women aged 40 - 59 who did or did not undergo mammography screening . Design Follow-up of r and omised screening trial by centre coordinators , the study ’s central office , and linkage to cancer registries and vital statistics data bases . Setting 15 screening centres in six Canadian provinces,1980 - 85 ( Nova Scotia , Quebec , Ontario , Manitoba , Alberta , and British Columbia ) . Participants 89 835 women , aged 40 - 59 , r and omly assigned to mammography ( five annual mammography screens ) or control ( no mammography ) . Interventions Women aged 40 - 49 in the mammography arm and all women aged 50 - 59 in both arms received annual physical breast examinations . Women aged 40 - 49 in the control arm received a single examination followed by usual care in the community . Main outcome measure Deaths from breast cancer . Results During the five year screening period , 666 invasive breast cancers were diagnosed in the mammography arm ( n=44 925 participants ) and 524 in the controls ( n=44 910 ) , and of these , 180 women in the mammography arm and 171 women in the control arm died of breast cancer during the 25 year follow-up period . The overall hazard ratio for death from breast cancer diagnosed during the screening period associated with mammography was 1.05 ( 95 % confidence interval 0.85 to 1.30 ) . The findings for women aged 40 - 49 and 50 - 59 were almost identical . During the entire study period , 3250 women in the mammography arm and 3133 in the control arm had a diagnosis of breast cancer , and 500 and 505 , respectively , died of breast cancer . Thus the cumulative mortality from breast cancer was similar between women in the mammography arm and in the control arm ( hazard ratio 0.99 , 95 % confidence interval 0.88 to 1.12 ) . After 15 years of follow-up a residual excess of 106 cancers was observed in the mammography arm , attributable to over-diagnosis . Conclusion Annual mammography in women aged 40 - 59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available . Overall , 22 % ( 106/484 ) of screen detected invasive breast cancers were over-diagnosed , representing one over-diagnosed breast cancer for every 424 women who received mammography screening in the trial To assess how women regard having had a false positive mammogram screening exam , and the influence that this had on their quality of life , 126 such women were interviewed . Their responses were compared to those of 152 women r and omly selected among screenees with a negative exam . Eighteen months after the screening the reported prevalence of anxiety about breast cancer was 29 % among women with a false positive and 13 % among women with a negative screening mammogram ( P = 0.001 ) . Of 30 women biopsied , 8 ( 27 % ) had pain in the breast and 10 ( 33 % ) had reduced sexual sensitivity . A false positive mammogram was described by 7 ( 5 % ) of the women as the worst thing they ever had experienced . However , most women with a false positive result regarded this experience , in retrospect , as but one of many minor stressful experiences creating a temporary decrease in quality of life . They report the same quality of life today as women with negative screening results and 98 % would attend another screening . Even so , false positive results are a matter of concern , and efforts should be made to minimise this cost whenever a screening programme is conducted PURPOSE To assess cancer detection rates , false-positive rates before arbitration , positive predictive values for women recalled after arbitration , and the type of cancers detected with use of digital mammography alone and combined with tomo synthesis in a large prospect i ve screening trial . MATERIAL S AND METHODS A prospect i ve , reader- and modality-balanced screening study of participants undergoing combined mammography plus tomo synthesis , the results of which were read independently by four different radiologists , is under way . The study was approved by a regional ethics committee , and all participants provided written informed consent . The authors performed a preplanned interim analysis of results from 12,631 examinations interpreted by using mammography alone and mammography plus tomo synthesis from November 22 , 2010 , to December 31 , 2011 . Analyses were based on marginal log-linear models for binary data , accounting for correlated interpretations and adjusting for reader-specific performance levels by using a two-sided significance level of .0294 . RESULTS Detection rates , including those for invasive and in situ cancers , were 6.1 per 1000 examinations for mammography alone and 8.0 per 1000 examinations for mammography plus tomo synthesis ( 27 % increase , adjusted for reader ; P = .001 ) . False-positive rates before arbitration were 61.1 per 1000 examinations with mammography alone and 53.1 per 1000 examinations with mammography plus tomo synthesis ( 15 % decrease , adjusted for reader ; P < .001 ) . After arbitration , positive predictive values for recalled patients with cancers verified later were comparable ( 29.1 % and 28.5 % , respectively , with mammography alone and mammography plus tomo synthesis ; P = .72 ) . Twenty-five additional invasive cancers were detected with mammography plus tomo synthesis ( 40 % increase , adjusted for reader ; P < .001 ) . The mean interpretation time was 45 seconds for mamm Output:	Overdiagnosed women may be harmed by unnecessary procedures and treatments as well as by the burden of receiving a cancer diagnosis .
MS21903	*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 effect of a single , oral bedtime dose of the benzodiazepine hypnotics flunitrazepam ( FR ; 2 mg ) , flurazepam ( FR ; 30 mg ) , and triazolam ( TR ; 0.5 mg ) on the sleep stages and the sleep EEG was investigated in eight healthy , young subjects . In comparison to the placebo night , all drugs reduced the percentage of stage 1 and REM sleep , increased stage 2 , and decreased the number of stage shifts . For FN and FR , some of these changes persisted in the postdrug night . All-night spectral analysis of the EEG showed a reduction of low-frequency activity ( 0.25 - 10.0 Hz ) in stages 2 , 3 + 4 and REM sleep , changes that persisted for all three drugs in the post-drug night . In the drug nights , activity in the spindle frequency range ( 11 - 14 Hz ) was enhanced particularly in stage 2 and 3 + 4 , activity in the high frequency range ( 17 - 25 Hz ) particularly in REM sleep and stage 1 . In the first third of the drug night , the depression of low-frequency activity in stage 2 was either absent ( FR ) or less prominent ( FN , TR ) than in the following part of the night . The results demonstrate that benzodiazepine hypnotics induce specific changes in the EEG spectra which reflect the immediate and residual drug effects more sensitively than conventional sleep scores We have evaluated the perioperative effects of melatonin with those of midazolam in 75 women in a prospect i ve , r and omized , double-blind , placebo-controlled study . Patients were given sublingual midazolam 15 mg , melatonin 5 mg or placebo , approximately 100 min before a st and ard anaesthetic . Sedation , anxiety and orientation were quantified before , and 10 , 30 , 60 and 90 min after premedication , and 15 , 30 , 60 and 90 min after admission to the recovery room . Psychomotor performance was evaluated at these times also , using the digit-symbol substitution test ( DSST ) and the Trieger dot test ( TDT ) . Patients who received premedication with either midazolam or melatonin had a significant decrease in anxiety levels and increase in levels of sedation before operation compared with controls . Midazolam produced the highest scores for sedation at 30 and 60 min after administration and significant psychomotor impairment in the preoperative period compared with melatonin or placebo . After operation , patients who received midazolam or melatonin premedication had increased levels of sedation at 30 min and impairment in performance on the DSST at 15 , 30 and 90 min compared with controls . There were no significant differences between the three groups for anxiety levels or TDT performance after operation . Amnesia was notable only in the midazolam group for one preoperative event ( entry into the operating room ) . Patient satisfaction was noted in the midazolam and melatonin groups only . We have demonstrated that melatonin can be used effectively for premedication of adult patients Postoperative pain can have a significant effect on patient recovery . An underst and ing of patient attitudes and concerns about postoperative pain is important for identifying ways health care professionals can improve postoperative care . To assess patients ’ postoperative pain experience and the status of acute pain management , we conducted a national study by using telephone question naires . A r and om sample of 250 adults who had undergone surgical procedures recently in the United States was obtained from National Family Opinion . Patients were asked about the severity of postsurgical pain , treatment , satisfaction with pain medication , patient education , and perceptions about postoperative pain and pain medications . Approximately 80 % of patients experienced acute pain after surgery . Of these patients , 86 % had moderate , severe , or extreme pain , with more patients experiencing pain after discharge than before discharge . Experiencing postoperative pain was the most common concern ( 59 % ) of patients . Almost 25 % of patients who received pain medications experienced adverse effects ; however , almost 90 % of them were satisfied with their pain medications . Approximately two thirds of patients reported that a health care professional talked with them about their pain . Despite an increased focus on pain management programs and the development of new st and ards for pain management , many patients continue to experience intense pain after surgery . Additional efforts are required to improve patients ’ postoperative pain experience The objective of the present study was to assess the toxicology of melatonin ( 10 mg ) , administered for 28 days to 40 volunteers r and omly assigned to groups receiving either melatonin ( N = 30 ) or placebo ( N = 10 ) in a double-blind fashion . The following measurements were performed : polysomnography ( PSG ) , laboratory examinations , including complete blood count , urinalysis , sodium , potassium and calcium levels , total protein levels , albumin , blood glucose , triglycerides , total cholesterol , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) , and very low-density lipoprotein ( VLDL ) , urea , creatinine , uric acid , glutamic-oxalacetic transaminase ( GOT ) , glutamic-pyruvate transaminase ( GPT ) , bilirubin , alkaline phosphatase , gama-glutamic transaminase ( GGT ) , T3 , T4 , TSH , LH/FSH , cortisol , and melatonin serum concentrations . In addition , the Epworth Somnolence Scale ( ESS ) and a sleep diary ( SD ) were also applied to the volunteers 1 wk before each PSG . In addition , the volunteers were asked about possible side effects ( SE ) that appeared during the treatment . The study was carried out according to the following timetable : Visit 0 , filling out the term of consent and inclusion criteria ; Visit 1 , PSG , laboratory examinations , ESS , SD , melatonin serum concentrations ; Visit 2 , SD , melatonin serum concentrations , SE ; Visit 3 , melatonin serum concentrations , PSG , ESS , SE ; Visit 4 , laboratory examinations , SE , melatonin serum concentrations , SD ; and Visit 5 , PSG , ESS , SE . Analysis of the PSG showed a statistically significant reduction of stage 1 of sleep in the melatonin group . No other differences between the placebo and melatonin groups were obtained . In the present study we did not observe , according to the parameters analyzed , any toxicological effect that might compromise the use of melatonin at a dose of 10 mg for the period of time utilized in this study BACKGROUND : The effect of melatonin on the intraoperative requirements for IV anesthetics has not been documented . We studied the effect of melatonin premedication on the propofol and thiopental dose – response curves for abolition of responses to verbal comm and s and eyelash stimulation . METHODS : This prospect i ve , r and omized , double-blind study included 200 adults with ASA physical status I. Patients received either 0.2 mg/kg melatonin or a placebo orally for premedication ( n = 100 per group ) . Approximately 50 min later , subgroups of 10 melatonin and 10 placebo patients were administered various doses of propofol ( 0.5 , 1.0 , 1.5 , 2.0 , or 2.4 mg/kg ) or thiopental ( 2.0 , 3.0 , 4.0 , 5.0 , or 6.0 mg/kg ) for anesthetic induction . The ability of each patient to respond to the comm and , “ open your eyes , ” and the disappearance of the eyelash reflex were assessed 60 s after the end of the injection of propofol or thiopental . Dose – response curves were determined by probit analysis . RESULTS : Melatonin premedication decreased thiopental ED50 values for loss of response to verbal comm and and eyelash reflex from 3.4 mg/kg ( 95%confidence interval , 3.2–3.5 mg/kg ) and 3.7 mg/kg ( 3.5–3.9 mg/kg ) to 2.7 mg/kg ( 2.6–2.9 mg/kg ) and 2.6 mg/kg ( 2.5–2.7 mg/kg ) , respectively ( P < 0.05 ) . Corresponding propofol ED50 values decreased from 1.5 mg/kg ( 1.4–1.6 mg/kg ) and 1.6 mg/kg ( 1.5–1.7 mg/kg ) to 0.9 mg/kg ( 0.8–0.96 mg/kg ) and 0.9 mg/kg ( 0.8–0.95 mg/kg ) , respectively ( P < 0.05 ) . CONCLUSIONS : Melatonin premedication significantly decreased the doses of both propofol and thiopental required to induce anesthesia BACKGROUND Iletrospective studies fail to identify predictors of postoperative nausea and vomiting ( PONV ) . The authors prospect ively studied 17,638 consecutive out patients who had surgery to identify predictors . METHODS Data on medical conditions , anesthesia , surgery , and PONV were collected in the post-anesthesia care unit , in the ambulatory surgical unit , and in telephone interviews conducted 24 h after surgery . Multiple logistic regression with backward stepwise elimination was used to develop a predictive model An independent set of patients was used to vali date the model RESULTS Age ( younger or older ) , sex ( female or male ) , smoking status ( nonsmokers or smokers ) , previous PONV , type of anesthesia ( general or other ) , duration of anesthesia ( longer or shorter ) , and type of surgery ( plastic , orthopedic shoulder , or other ) were independent predictors of PONV . A 10-yr increase in age decreased the likelihood of PONV by 13 % . The risk for men was one third that for women . A 30-min increase in the duration of anesthesia increased the likelihood of PONV by 59 % . General anesthesia increased the likelihood of PONV 11 times compared with other types of anesthesia . Patients with plastic and orthopedic shoulder surgery had a sixfold increase in the risk for PONV . The model predicted PONV accurately and yielded an area under the receiver operating characteristic curve of 0.785+/-0.011 using an independent validation set . CONCLUSIONS A vali date d mathematical model is provided to calculate the risk of PONV in out patients having surgery . Knowing the factors that predict PONV will help anesthesiologists determine which patients will need antiemetic therapy Melatonin has been reported to reduce preoperative anxiety . We performed this study to compare preoperative anxiety in elderly patients receiving melatonin ( M ) or placebo ( P ) . Anxiety was measured in patients aged > 65 yr by a numerical rating scale ( range , 0–10 ) . Each patient was r and omized to receive M 10 mg or P orally : 71 patients were in group P and 67 in group M. The median ( quartiles ) anxiety level was 5 ( 2–8 ) before and 3 ( 1–7 ) 90 min after premedication in group M and 5 ( 3–6 ) and 3 ( 1–5 ) in group P , respectively . M and P reduce anxiety in elderly patients to a similar degree Midazolam ( 15 mg p.o . ) was compared with placebo and oxazepam ( 15 mg ) in 12 healthy volunteers and in seven patients suffering from sleep disorders in a single-blind cross-over study . Each treatment period lasted for seven days . The last two nights were spent in a sleep laboratory to evaluate the efficacy of the three compounds . The drugs were given to the patients every day and to the volunteers only on the recorded nights immediately before going to bed . The subjects rated their quality of sleep every morning after administration . Midazolam shortened ( P = 0.025 ) the sleep latency to first stage 2 ( t2 = 29 min ) compared with placebo ( t2 = 58.7 ) min and oxazepam ( t2 = 55.4 min ) in the group of patients ; in the group of volunteers t2 was shortened ( P = 0.05 ) only by midazolam ( t2 = 17.2 min ) compared with placebo ( t2 = 24.6 min ) . REM suppression was not found in the group of patients , while sleep stages 3 + 4 were slightly reduced . However , a suppression of REM by midazolam ( P = 0.025 ) and oxazepam ( P = 0.01 ) was observed in the volunteers compared with placebo . The effects of midazolam seemed to be related to its pharmacokinetics . The drug increased the amount of stage 3 + 4 ( P = 0.01 ) and suppressed REM ( P = 0.005 ) compared with oxazepam and placebo , only during the first 3 h , when it was measurable in plasma . Midazolam was rated by the patients more favourably than oxazepam ( P = 0.025 ) and placebo ( P = 0.05 ) . The volunteers noted no difference amongst the three treatments , but reported hangover effects after oxazepam BACKGROUND : Melatonin has anxiolytic and potential analgesic effects . In this study , we assessed the effects of melatonin premedication on pain , anxiety , intraocular pressure ( IOP ) , and operative conditions during cataract surgery under topical analgesia . METHODS : Forty patients undergoing cataract surgery under topical anesthesia were r and omly assigned Output:	Thus , melatonin premedication is effective in ameliorating preoperative anxiety in adults , but its analgesic effects remain controversial in the perioperative period .
MS21904	*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 suggests that flavonoid-containing diets reduce cardiovascular risk , but the mechanisms responsible are unclear . In the present study , we sought to determine the effect of flavanol-rich cocoa on vascular function in individuals with CAD ( coronary artery disease ) . Forty subjects ( 61+/-8 years ; 30 male ) with CAD were recruited to a 6-week r and omized double-blind placebo-controlled study . Subjects consumed either a flavanol-rich chocolate bar and cocoa beverage daily ( total flavanols , 444 mg/day ) or matching isocaloric placebos daily ( total flavanols , 19.6 mg/day ) for 6 weeks . Brachial artery FMD ( flow-mediated dilation ) and SAC ( systemic arterial compliance ) were assessed at baseline , 90 min following the first beverage and after 3 and 6 weeks of daily consumption . Soluble cellular adhesion molecules and FBF ( forearm blood flow ) responses to ACh ( acetylcholine chloride ; 3 - 30 microg/min ) and SNP ( sodium nitroprusside ; 0.3 - 3 microg/min ) infusions , forearm ischaemia and isotonic forearm exercise were assessed at baseline and after 6 weeks . FMD , SAC and FBF responses did not differ between groups at baseline . No acute or chronic changes in FMD or SAC were seen in either group . No difference in soluble cellular adhesion molecules , FBF responses to ischaemia , exercise , SNP or ACh was seen in the group receiving flavanol-rich cocoa between baseline and 6 weeks . These data suggest that over a 6-week period , flavanol-rich cocoa does not modify vascular function in patients with established CAD AIMS Flavanol-rich chocolate ( FRC ) is beneficial for vascular and platelet function by increasing nitric oxide bioavailability and decreasing oxidative stress . Congestive heart failure ( CHF ) is characterized by impaired endothelial and increased platelet reactivity . As statins are ineffective in CHF , alternative therapies are a clinical need . We therefore investigated whether FRC might improve cardiovascular function in patients with CHF . METHODS AND RESULTS Twenty patients with CHF were enrolled in a double-blind , r and omized placebo-controlled trial , comparing the effect of commercially available FRC with cocoa-liquor-free control chocolate ( CC ) on endothelial and platelet function in the short term ( 2 h after ingestion of a chocolate bar ) and long term ( 4 weeks , two chocolate bars/day ) . Endothelial function was assessed non-invasively by flow-mediated vasodilatation of the brachial artery . Flow-mediated vasodilatation significantly improved from 4.98 ± 1.95 to 5.98 ± 2.32 % ( P = 0.045 and 0.02 for between-group changes ) 2h after intake of FRC to 6.86 ± 1.76 % after 4 weeks of daily intake ( P = 0.03 and 0.004 for between groups ) . No effect on endothelial-independent vasodilatation was observed . Platelet adhesion significantly decreased from 3.9 ± 1.3 to 3.0 ± 1.3 % ( P = 0.03 and 0.05 for between groups ) 2 h after FRC , an effect that was not sustained at 2 and 4 weeks . Cocoa-liquor-free CC had no effect , either on endothelial function or on platelet function . Blood pressure and heart rate did not change in either group . CONCLUSION Flavanol-rich chocolate acutely improves vascular function in patients with CHF . A sustained effect was seen after daily consumption over a 4-week period , even after 12 h abstinence . These beneficial effects were paralleled by an inhibition of platelet function in the presence of FRC only The consumption of cocoa and dark chocolate is associated with a lower risk of CVD , and improvements in endothelial function may mediate this relationship . Less is known about the effects of cocoa/chocolate on the augmentation index ( AI ) , a measure of vascular stiffness and vascular tone in the peripheral arterioles . We enrolled thirty middle-aged , overweight adults in a r and omised , placebo-controlled , 4-week , cross-over study . During the active treatment ( cocoa ) period , the participants consumed 37 g/d of dark chocolate and a sugar-free cocoa beverage ( total cocoa = 22 g/d , total flavanols ( TF ) = 814 mg/d ) . Colour-matched controls included a low-flavanol chocolate bar and a cocoa-free beverage with no added sugar ( TF = 3 mg/d ) . Treatments were matched for total fat , saturated fat , carbohydrates and protein . The cocoa treatment significantly increased the basal diameter and peak diameter of the brachial artery by 6 % ( + 2 mm ) and basal blood flow volume by 22 % . Substantial decreases in the AI , a measure of arterial stiffness , were observed in only women . Flow-mediated dilation and the reactive hyperaemia index remained unchanged . The consumption of cocoa had no effect on fasting blood measures , while the control treatment increased fasting insulin concentration and insulin resistance ( P= 0·01 ) . Fasting blood pressure ( BP ) remained unchanged , although the acute consumption of cocoa increased resting BP by 4 mmHg . In summary , the high-flavanol cocoa and dark chocolate treatment was associated with enhanced vasodilation in both conduit and resistance arteries and was accompanied by significant reductions in arterial stiffness in women Cocoa flavanol ( CF ) intake improves endothelial function in patients with cardiovascular risk factors and disease . We investigated the effects of CF on surrogate markers of cardiovascular health in low risk , healthy , middle-aged individuals without history , signs or symptoms of CVD . In a 1-month , open-label , one-armed pilot study , bi-daily ingestion of 450 mg of CF led to a time-dependent increase in endothelial function ( measured as flow-mediated vasodilation ( FMD ) ) that plateaued after 2 weeks . Subsequently , in a r and omised , controlled , double-masked , parallel-group dietary intervention trial ( Clinical trials.gov : NCT01799005 ) , 100 healthy , middle-aged ( 35–60 years ) men and women consumed either the CF-containing drink ( 450 mg ) or a nutrient-matched CF-free control bi-daily for 1 month . The primary end point was FMD . Secondary end points included plasma lipids and blood pressure , thus enabling the calculation of Framingham Risk Scores and pulse wave velocity . At 1 month , CF increased FMD over control by 1·2 % ( 95 % CI 1·0 , 1·4 % ) . CF decreased systolic and diastolic blood pressure by 4·4 mmHg ( 95 % CI 7·9 , 0·9 mmHg ) and 3·9 mmHg ( 95 % CI 6·7 , 0·9 mmHg ) , pulse wave velocity by 0·4 m/s ( 95 % CI 0·8 , 0·04 m/s ) , total cholesterol by 0·20 mmol/l ( 95 % CI 0·39 , 0·01 mmol/l ) and LDL-cholesterol by 0·17 mmol/l ( 95 % CI 0·32 , 0·02 mmol/l ) , whereas HDL-cholesterol increased by 0·10 mmol/l ( 95 % CI 0·04 , 0·17 mmol/l ) . By applying the Framingham Risk Score , CF predicted a significant lowering of 10-year risk for CHD , myocardial infa rct ion , CVD , death from CHD and CVD . In healthy individuals , regular CF intake improved accredited cardiovascular surrogates of cardiovascular risk , demonstrating that dietary flavanols have the potential to maintain cardiovascular health even in low-risk subjects Consumption of flavanol-rich dark chocolate ( DC ) has been shown to decrease blood pressure ( BP ) and insulin resistance in healthy subjects , suggesting similar benefits in patients with essential hypertension ( EH ) . Therefore , we tested the effect of DC on 24-hour ambulatory BP , flow-mediated dilation ( FMD ) , and oral glucose tolerance tests ( OGTTs ) in patients with EH . After a 7-day chocolate-free run-in phase , 20 never-treated , grade I patients with EH ( 10 males ; 43.7±7.8 years ) were r and omized to receive either 100 g per day DC ( containing 88 mg flavanols ) or 90 g per day flavanol-free white chocolate ( WC ) in an isocaloric manner for 15 days . After a second 7-day chocolate-free period , patients were crossed over to the other treatment . Noninvasive 24-hour ambulatory BP , FMD , OGTT , serum cholesterol , and markers of vascular inflammation were evaluated at the end of each treatment . The homeostasis model assessment of insulin resistance ( HOMA-IR ) , quantitative insulin sensitivity check index ( QUICKI ) , and insulin sensitivity index ( ISI ) were calculated from OGTT values . Ambulatory BP decreased after DC ( 24-hour systolic BP −11.9±7.7 mm Hg , P<0.0001 ; 24-hour diastolic BP −8.5±5.0 mm Hg , P<0.0001 ) but not WC . DC but not WC decreased HOMA-IR ( P<0.0001 ) , but it improved QUICKI , ISI , and FMD . DC also decreased serum LDL cholesterol ( from 3.4±0.5 to 3.0±0.6 mmol/L ; P<0.05 ) . In summary , DC decreased BP and serum LDL cholesterol , improved FMD , and ameliorated insulin sensitivity in hypertensives . These results suggest that , while balancing total calorie intake , flavanols from cocoa products may provide some cardiovascular benefit if included as part of a healthy diet for patients with EH To assess whether antioxidant , anti-inflammatory and other cardio-protective effects attributed to cocoa are achieved when regularly consuming moderate amounts of a flavanol-rich soluble cocoa product , a non-r and omized , controlled , crossover , free-living study was carried out in healthy ( n = 24 ; 25.9 ± 5.6 years ) and moderately hypercholesterolemic ( 200 - 240 mg dL(-1 ) ; n = 20 ; 30.0 ± 10.3 years ) volunteers . Participants consumed two servings per day ( 7.5 g per serving ) of a soluble cocoa product ( providing 45.3 mg flavanols per day ) in milk , which was compared with consuming only milk during a 4 week period . The effects on systolic and diastolic blood pressure and heart rate were determined , as well as on serum lipid and lipoprotein profiles , interleukins (IL)-1β , IL-6 , IL-8 , IL-10 , tumor necrosis factor-α ( TNF-α ) , monocyte chemoattractant protein-1 ( MCP-1 ) , vascular ( VCAM-1 ) and intercellular cell adhesion molecules ( ICAM-1 ) , serum malondialdehyde ( MDA ) , carbonyl groups ( CG ) , ferric reducing/antioxidant power ( FRAP ) , oxygen radical absorbance capacity ( ORAC ) , and free radical scavenging capacity ( ABTS ) . During the study , the volunteers ' diets and physical activity were also evaluated , as well as any changes in weight , skin folds , circumferences and related anthropometric parameters . Cocoa and certain polyphenol-rich fruits and vegetables and their derivatives were restricted . After consuming the cocoa product positive effects were observed such as an increase in serum HDL-C ( p < 0.001 ) and dietary fiber intake ( p = 0.050 ) , whereas IL-10 decreased ( p = 0.022 ) . Other cardiovascular-related biomarkers and anthropometric parameters were unaffected . We have therefore concluded that regular consumption of this cocoa product in a Spanish-Mediterranean diet may protect against cardiovascular disease in healthy and hypercholesterolemic subjects without producing any weight gain or other anthropometric changes Increased vascular stiffness , endothelial dysfunction , and isolated systolic hypertension are hallmarks of vascular aging . Regular cocoa flavanol ( CF ) intake can improve vascular function in healthy young and elderly at-risk individuals . However , the mechanisms underlying CF bioactivity remain largely unknown . We investigated the effects of CF intake on cardiovascular function in healthy young and elderly individuals without history , signs , or symptoms of cardiovascular disease by applying particular focus on functional endpoints relevant to cardiovascular aging . In a r and omized , controlled , double-masked , parallel-group dietary intervention trial , 22 young ( < 35 years ) and 20 elderly ( 50–80 year ) healthy , male non-smokers consumed either a CF-cont Output:	The control group received either a flavanol-free product ( n = 26 treatment comparisons ) or a low-flavanol-containing cocoa powder ( range 6.4 to 88 mg flavanols ( mean = 55 mg , 13 treatment comparisons ; 259 mg , 1 trial).Meta-analyses of the 40 treatment comparisons involving 1804 mainly healthy participants revealed a small but statistically significant blood pressure-reducing effect of flavanol-rich cocoa products compared with control in trials of two to 18 weeks duration ( mean nine weeks):Mean difference systolic blood pressure ( SBP ) ( 95 % confidence interval ( CI ) : -1.76 ( -3.09 to -0.43 ) mmHg , P = 0.009 , n = 40 treatment comparisons , 1804 participants ; Mean difference diastolic blood pressure ( DBP ) ( 95 % CI ) : -1.76 ( -2.57 to -0.94 ) mmHg , P < 0.001 , n = 39 treatment comparisons , 1772 participants .Baseline blood pressure may play a role in the effect of cocoa on blood pressure . While systolic blood pressure was reduced significantly by 4 mmHg in hypertensive people ( n = 9 treatment comparisons , 401 participants ) , and tended to be lowered in prehypertensive people ( n= 8 treatment comparisons , 340 participants ) , there was no significant difference in normotensive people ( n = 23 treatment comparisons , 1063 participants ) ; however , the test for subgroup differences was of borderline significance ( P = 0.08 ; I2 = 60 % ) , requiring further research to confirm the findings .Subgroup meta- analysis by blinding suggested a trend towards greater blood pressure reduction in unblinded trials compared to double-blinded trials , albeit statistically not significant . Subgroup analysis by type of control ( flavanol-free versus low-flavanol control ) did not reveal a significant difference . This review provides moderate- quality evidence that flavanol-rich chocolate and cocoa products cause a small ( 2 mmHg ) blood pressure-lowering effect in mainly healthy adults in the short term . These findings are limited by the heterogeneity between trials , which could not be explained by prespecified subgroup analyses , including blinding , flavanol content of the control groups , age of participants , or study duration .
MS21905	*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 Rapamycin-eluting stents ( RES ) have been shown to reduce restenosis in many types of lesions . However , the ideal strategy for the treatment of coronary bifurcated lesions has not been established to date . This r and omized study compares 2 strategies for the RES treatment of bifurcation lesions : a simple approach ( stenting the main vessel and balloon dilatation for the side branch [ SB ] ) versus a complex approach ( stents for both vessels ) . METHODS To compare both strategies , a r and omized study was conducted in 91 patients with true coronary bifurcation lesions . All patients received an RES at the main vessel , covering the SB . Patients from group A ( n = 47 ) were assigned to balloon dilation of the involved SB ( simple strategy ) ; patients in group B ( n = 44 ) were r and omized to receive a second stent at the SB origin ( complex strategy ) . There were no differences between groups regarding baseline clinical and angiographic data . RESULTS Major adverse cardiac events occurred in 3 patients from group A ( 2 non-Q-wave myocardial infa rct ions and 1 target lesion revascularization ) . Six-month angiographic reevaluation was obtained in 80 patients ( 88 % ) . Restenosis of the main vessel was observed in 1 ( 2 % ) patient from group A and in 4 ( 10 % ) from group B. Restenosis of the SB appeared in 2 ( 5 % ) patients from group A and in 6 ( 15 % ) from group B. CONCLUSIONS Both strategies are effective in reducing the restenosis rate , with no differences in terms of clinical outcome . Elective SB stenting seems to provide no advantages over the simpler stent jail followed by SB balloon dilation OBJECTIVES This study sought to evaluate the optimal percutaneous coronary intervention techniques using drug-eluting stents for bifurcation coronary lesions . BACKGROUND The optimal bifurcation stenting technique needs to be evaluated . METHODS The trial included 2 r and omization studies separated by the presence of side branch ( SB ) stenosis for patients having non-left main bifurcation lesions . For 306 patients without SB stenosis , the routine final kissing balloon or leave-alone approaches were compared . Another r and omization study compared the crush or single-stent approaches for 419 patients with SB stenosis . RESULTS Between the routine final kissing balloon and leave-alone groups for nondiseased SB lesions , angiographic restenosis occurred in 17.9 % versus 9.3 % ( p=0.064 ) , comprising 15.1 % versus 3.7 % for the main branch ( p=0.004 ) and 2.8 % versus 5.6 % for the SB ( p=0.50 ) from 214 patients ( 69.9 % ) receiving 8-month angiographic follow-up . Incidence of major adverse cardiac events including death , myocardial infa rct ion , or target vessel revascularization over 1 year was 14.0 % versus 11.6 % between the routine final kissing balloon and leave-alone groups ( p=0.57 ) . In another r and omization study for diseased SB lesions , 28.2 % in the single-stent group received SB stents . From 300 patients ( 71.6 % ) receiving angiographic follow-up , between the crush and single-stent groups , angiographic restenosis rate was 8.4 % versus 11.0 % ( p=0.44 ) , comprising 5.2 % versus 4.8 % for the main branch ( p=0.90 ) and 3.9 % versus 8.3 % for the SB ( p=0.12 ) . One-year major adverse cardiac events rate between the crush and single-stent groups was 17.9 % versus 18.5 % ( p=0.84 ) . CONCLUSIONS Angiographic and clinical outcomes were excellent after percutaneous coronary intervention using drug-eluting stents with any stent technique for non-left main bifurcation lesions once the procedure was performed successfully We compared the myocardial ischemic burden of provisional and routine final kissing-balloon inflation ( FKI ) with the 1-stent strategy using a second-generation drug-eluting stent for coronary bifurcation lesions ( CBL ) . There are no established guidelines for side branch ( SB ) intervention after main vessel stenting . In total , 113 CBL patients were r and omized to receive different SB intervention strategies : provisional-FKI group ( n = 57 ; FKI only when SB flow was TIMI <3 ) and routine-FKI group ( n = 56 ; m and atory FKI with aggressive treatment until SB-residual stenosis < 50 % ) . Dipyridamole-stress myocardial perfusion scintigraphy with 99mTc was performed after 8 months . The regional summed-difference score ( r-SDS ) was calculated according to the coronary territory . The primary endpoint included target vessel ischemia ( TVI ; r-SDS ≥ 2 ) at 8 months , whereas the clinical primary endpoint was major adverse cardiovascular events ( MACE ) at 3 years . The percent ( % ) myocardial ischemia ( 100 × SDS/68 ) was also calculated . At 8 months , TVI was identified in 11 and 4 % in the provisional-FKI and routine-FKI groups , respectively ( p = 0.226 ) . SB-binary restenosis ( 48 vs. 4 % , p < 0.001 ) and myocardial ischemia at the SB territory ( 11 vs. 0 % , p = 0.030 ) were more common in the provisional-FKI group ; however , in TVI patients , % myocardial ischemia ( 4.12 ± 1.23 % vs. 3.68 ± 1.04 % ; p = 0.677 ) did not significantly differ . Moderate/severe ischemia ( > 10 % myocardial ischemia ) was not observed in the target vessel in either group . Long-term cumulative MACE were similar between the groups ( 9 vs. 14 % ; p = 0.358 ) . Provisional-FKI according to TIMI-SB flow grade led to similar and acceptable myocardial ischemia , in comparison with routine-FKI , which may contribute to the identical long-term follow-up Final kissing-balloon inflation is often recommended for percutaneous coronary intervention ( PCI ) of bifurcation lesions . However , r and omized trials focusing on kissing inflation have not confirmed its beneficial impact . We compared outcomes of kissing inflation for PCI of bifurcation lesions , explicitly stratifying results according to stenting strategy . Patients undergoing bifurcation PCI were retrospectively enrolled . Subjects receiving final kissing inflation were compared with those not undergoing kissing inflation , after stratification for a single-stent technique . The primary end point was the long-term rate of major adverse cardiac events ( MACE , i.e. , death , myocardial infa rct ion , or target lesion revascularization ( TLR ) ) . A total of 4314 patients were included : 1176 ( 27.3 % ) treated with a single stent and kissing inflation , 1637 ( 37.9 % ) with a single stent but no kissing , 1072 ( 24.8 % ) with two stents and kissing , and 429 ( 9.9 % ) with two stents but no kissing . At unadjusted analyses kissing was associated with fewer short-term MACE and deaths in the two-stent group , and with fewer long-term MACE , cardiac deaths , and side-branch TLR in the two-stent group ( all P < 0.05 ) . Conversely , kissing appeared detrimental after single stenting . However , after multivariable analyses , kissing no longer significantly affected the risk of adverse events , with the exception of the risk of side-branch TLR , which was lower in those receiving two stents and final kissing inflation ( hazard ratio = 0.52 , 95 % confidence interval 0.30–0.90 , P = 0.020 ) . Kissing inflation can be avoided in bifurcation lesions uneventfully treated with single-stent PCI . However , final kissing-balloon inflation appears beneficial in reducing the risk of side-branch repeat revascularization after using a two-stent strategy Background — It is unknown whether the preferred 1-stent bifurcation stenting approach with stenting of the main vessel ( MV ) and optional side branch stenting using drug-eluting stents should be finalized by a kissing balloon dilatation ( FKBD ) . Therefore , we compared strategies of MV stenting with and without FKBD . Methods and Results — We r and omized 477 patients with a bifurcation lesion to FKBD ( n=238 ) or no FKBD ( n=239 ) after MV stenting . The primary end point was major adverse cardiac events : cardiac death , non – procedure-related index lesion myocardial infa rct ion , target lesion revascularization , or stent thrombosis within 6 months . The 6-month major adverse cardiac event rates were 2.1 % and 2.5 % ( P=1.00 ) in the FKBD and no-FKBD groups , respectively . Procedure and fluoroscopy times were longer and more contrast media was needed in the FKBD group than in the no-FKBD group . Three hundred twenty-six patients had a quantitative coronary assessment . At 8 months , the rate of binary (re)stenosis in the entire bifurcation lesion ( MV and side branch ) was 11.0 % versus 17.3 % ( P=0.11 ) , in the MV was 3.1 % versus 2.5 % ( P=0.68 ) , and in the side branch was 7.9 % versus 15.4 % ( P=0.039 ) in the FKBD versus no-FKBD groups , respectively . In patients with true bifurcation lesions , the side branch restenosis rate was 7.6 % versus 20.0 % ( P=0.024 ) in the FKBD and no-FKBD groups , respectively . Conclusions — MV stenting strategies with and without FKBD were associated with similar clinical outcomes . FKBD reduced angiographic side branch (re)stenosis , especially in patients with true bifurcation lesions . The simple no-FKBD procedures result ed in reduced use of contrast media and shorter procedure and fluoroscopy times . Long-term data on stent thrombosis are needed . Clinical Trial Registration — URL : http:// clinical trials.gov . Unique identifier : NCT00914199 Background —Treatment of bifurcations is a complex problem . The clinical value of treating side branches is an unsolved problem in the field of interventional cardiology . Methods and Results —We initiated a prospect i ve r and omized controlled trial . One hundred and ten patients with bifurcations were r and omly assigned to 2 arms : Stenting of the main branch ( MB , Taxus-stent , paclitaxel-eluting stents ) and m and atory side branch ( SB ) percutaneous coronary intervention ( PCI ; kissing balloons ) with provisional SB stenting ( therapy A ) , or stenting of the MB ( paclitaxel-eluting stents ) with provisional SB-PCI only when the SB had a thrombolysis in myocardial infa rct ion flow < 2 ( therapy B ) . The primary end point was target lesion revascularization . The mean ages were 66.8 years ( A ) versus 65.1 years ( B , P=0.4 ) , 71.4 % ( A ) versus 77.8 % were men ( P=0.4 ) , patients with diabetes were present in 25.0 % versus 25.9 % ( P=0.9 ) . The MB was left anterior descending artery in 80.4 % versus 81.5 % ( A versus B , P=0.9 ) . The SB-PCI and kissing balloon-PCI were performed according to the study protocol in 82.1%/73.2 % versus 16.7%/13.0 % ( P<0.05 for both ) , while changing of the intended therapy was necessary in 17.9 % versus 16.7 % ( A versus B , P=0.9 ) . A final thrombolysis in myocardial infa rct ion flow 3 ( MB ) was reached in all patients ( groups A and B ) , final thrombolysis in myocardial infa rct ion flow 3 ( SB ) was observed in 96.4 % versus 88.9 % ( A versus B , P=0.3 ) . Radiation time ( min ) and contrast medium ( mL ) were 14.2/210 ( group A ) versus 7.8/151.6 ( group B ; P for both < 0.05 ) . Six month – follow up : major adverse cardiac events was 23.2 % ( A ) versus 24.1 % ( B , P=0.9 ) , target lesion revascularization was 17.9 % ( A ) versus 14.8 % ( B , P=0.7 ) , and late lumen loss ( MB ) was 0.2 mm ( A ) versus 0.3 mm ( B , P=0.5 ) . In group B , no PCI of the SB was done during follow up . Conclusion —A simple strategy using paclitaxel-eluting stents with only provisional Output:	Compared with the No-KBI strategy , the KBI strategy reduced the incidence of side branch restenosis and increased the risk of main branch restenosis in the one-stent approach . However , the clinical outcomes were similar between the KBI and No-KBI groups
MS21906	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Hypertension is the leading risk factor responsible for premature death worldwide , but its burden has shifted to low- and middle-income countries . Therefore , we studied hypertension and cardiovascular risk in the population of Suriname , a middle-income country with a predominantly urban population of African and Asian ancestry . METHODS A r and om sample of 1,800 noninstitutionalized men and women aged 18 - 70 years was selected to be interviewed at home and examined at the local hospital for cardiovascular risk factors , asymptomatic organ damage , and cardiovascular disease . RESULTS The 1,157 participants examined ( 37 % men ) were mainly of self-defined Asian ( 43 % ) or African ( 39 % ) ancestry , mean age 43 years ( SD 14 ) . The majority of the population ( 71 % ) had hypertension or prehypertension , respectively , 40 % and 31 % . Furthermore , 72 % was obese or overweight , while 63 % had diabetes or prediabetes . Only 1 % of the adult population had an optimal cardiovascular risk profile . Hypertension awareness , treatment , and control were respectively 68 % , 56 % , and 20 % . In line with this , 22 % of the adult population had asymptomatic organ damage , including increased arterial stiffness , left ventricular hypertrophy , microalbuminuria , or asymptomatic chronic kidney disease . CONCLUSIONS In this first extensive cardiovascular assessment in the general population of this middle-income Caribbean country , high prevalence of hypertension with inadequate levels of treatment and control was predominant . The findings emphasize the need for collaborative effort from national and international bodies to prioritize the implementation of affordable and sustainable public health programs that combat the escalating hypertension and cardiovascular risk factor burden OBJECTIVE We evaluated the effects of exercise on neurobehavioral function in healthy older people more than 75 years of age . DESIGN A r and omized controlled trial with 6-month follow-up was conducted . SETTING The study was performed in the rural town of Kahoku , Japan , the population of which is considered representative of the older population of Japan . PARTICIPANTS We studied 42 healthy volunteers ( 18 men and 24 women ; mean age , 79 years ( range 75 to 87 years ) ) who were r and omly assigned to one of two groups , exercise or control . INTERVENTION Subjects assigned to the exercise group were instructed to exercise for 60 minutes twice a week for 6 months . Subjects in the control group were not instructed to engage in an specific exercise regimen . MEASUREMENTS The following measurements were recorded for both groups at baseline and at 6-month follow-up : ( 1 ) Neurobehavioral function as determined by the following tests : Mini-Mental State Exam ( MMSE ) , Hasegawa Dementia Scale Revised ( HDSR ) , Visuospatial Cognitive Performance Test ( VCP-test ) , Button score , Up & Go test , and Functional Reach ; and ( 2 ) Body mass index and blood pressure . RESULTS The effects of exercise were shown in the Up & Go test , and Functional Reach ( ANOVA with repeated measures ) . CONCLUSION This study demonstrates the acceptability and effectiveness of exercise on neurobehavioral function , even in older people more than 75 years of age Background Both exercise training and diet are recommended to prevent and control hypertension and overweight/obesity . Purpose The purpose of this study was to determine the effectiveness of different 16-week aerobic exercise programmes with hypocaloric diet on blood pressure , body composition , cardiorespiratory fitness and pharmacological treatment . Methods Overweight/obese , sedentary participants ( n = 175 , aged 54.0 ± 8.2 years ) with hypertension were r and omly assigned into an attention control group ( physical activity recommendations ) or one of three supervised exercise groups ( 2 days/week : high-volume with 45 minutes of moderate-intensity continuous training ( MICT ) , high-volume and high-intensity interval training ( HIIT ) , alternating high and moderate intensities , and low-volume HIIT ( 20 minutes ) ) . All variables were assessed pre- and post-intervention . All participants received the same hypocaloric diet . Results Following the intervention , there was a significant reduction in blood pressure and body mass in all groups with no between-group differences for blood pressure . However , body mass was significantly less reduced in the attention control group compared with all exercise groups ( attention control –6.6 % , high-volume MICT –8.3 % , high-volume HIIT –9.7 % , low-volume HIIT –6.9 % ) . HIIT groups had significantly higher cardiorespiratory fitness than high-volume MICT , but there were no significant between-HIIT differences ( attention control 16.4 % , high-volume MICT 23.6 % , high-volume HIIT 36.7 % , low-volume HIIT 30.5 % ) . Medication was removed in 7.6 % and reduced in 37.7 % of the participants . Conclusions The combination of hypocaloric diet with supervised aerobic exercise 2 days/week offers an optimal non-pharmacological tool in the management of blood pressure , cardiorespiratory fitness and body composition in overweight/obese and sedentary individuals with hypertension . High-volume HIIT seems to be better for reducing body mass compared with low-volume HIIT . The exercise-induced improvement in cardiorespiratory fitness is intensity dependent with low-volume HIIT as a time-efficient method in this population . Clinical Trials.gov Registration : NCT02283047 Introduction : Several established tools are available to assess study quality and reporting of r and omized controlled trials ; however , these tools were design ed with clinical intervention trials in mind . In exercise training intervention trials some of the traditional study quality criteria , such as participant or research er blinding , are extremely difficult to implement . Methods : We developed the Tool for the assEssment of Study qualiTy and reporting in EXercise ( TESTEX ) – a study quality and reporting assessment tool , design ed specifically for use in exercise training studies . Our tool is a 15-point scale ( 5 points for study quality and 10 points for reporting ) and addresses previously unmentioned quality assessment criteria specific to exercise training studies . Results : There were no systematic differences between the summated TESTEX scores of each observer [ H(2 ) = 0.392 , P = 0.822 ] . There was a significant association between the summated TESTEX scores of the three observers , with almost perfect agreement between observers 1 and 2 [ intra-class correlation coefficient ( ICC ) = 0.93 , 95 % confidence interval ( CI ) 0.82–0.97 , P < 0.001 ] , observers 1 and 3 ( ICC = 0.96 , 95 % CI 0.89–0.98 , P < 0.001 ) and observers 2 and 3 ( ICC = 0.91 , 95 % CI 0.75–0.96 , P < 0.001 ) . Conclusions : The TESTEX scale is a new , reliable tool , specific to exercise scientists , that facilitates a comprehensive review of exercise training trials The effects of long-term aerobic exercise on endothelial function in patients with essential hypertension remain unclear . To determine whether endothelial function relating to forearm hemodynamics in these patients differs from normotensive subjects and whether endothelial function can be modified by continued physical exercise , we r and omized patients with essential hypertension into a group that engaged in 30 minutes of brisk walking 5 to 7 times weekly for 12 weeks ( n=20 ) or a group that underwent no activity modifications ( control group , n=7 ) . Forearm blood flow was measured using strain-gauge plethysmography during reactive hyperemia to test for endothelium-dependent vasodilation and after sublingual nitroglycerin administration to test endothelium-independent vasodilation . Forearm blood flow in hypertensive patients during reactive hyperemia was significantly less than that in normotensive subjects ( n=17 ) . Increases in forearm blood flow after nitroglycerin were similar between hypertensive and normotensive subjects . Exercise lowered mean blood pressure from 115.7+/-5.3 to 110.2+/-5.1 mm Hg ( P<0.01 ) and forearm vascular resistance from 25.6+/-3.2 to 23 . 2+/-2.8 mm Hg/mL per minute per 100 mL tissue ( P<0.01 ) ; no change occurred in controls . Basal forearm blood flow , body weight , and heart rate did not differ with exercise . After 12 weeks of exercise , maximal forearm blood flow response during reactive hyperemia increased significantly , from 38.4+/-4.6 to 47.1+/-4.9 mL/min per 100 mL tissue ( P<0.05 ) ; this increase was not seen in controls . Changes in forearm blood flow after sublingual nitroglycerin administration were similar before and after 12 weeks of exercise . Intra-arterial infusion of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine abolished the enhancement of reactive hyperemia induced by 12 weeks of exercise . These findings suggest that through increased release of nitric oxide , continued physical exercise alleviates impairment of reactive hyperemia in patients with essential hypertension Background —Reductions in the compliance of central arteries exert a number of adverse effects on cardiovascular function and disease risk . Endurance training is efficacious in increasing arterial compliance in healthy adults . We determined the effects of resistance training on carotid arterial compliance using the intervention study design . Methods and Results —Twenty-eight healthy men 20 to 38 years old were r and omly assigned to the intervention group ( n=14 ) and the control group ( n=14 ) . Control subjects were instructed not to alter their normal activity levels throughout the study period . Intervention subjects underwent 3 supervised resistance training sessions per week for 4 months and detraining for a subsequent 4 months . The resistance training increased maximal strength in all muscle groups tested ( P<0.001 ) . There were no significant differences in baseline arterial compliance and & bgr;-stiffness index between the intervention and control groups . In the intervention group , carotid arterial compliance decreased 19 % ( P<0.05 ) , and & bgr;-stiffness index increased 21 % ( P<0.01 ) after resistance training . These values returned completely to the baseline levels during the detraining period . Arterial compliance did not change in the control group . In both groups , there were no significant changes in brachial and carotid blood pressure , carotid intima-media thickness , lumen diameter , and femoral arterial compliance . Changes in carotid artery compliance were significantly and negatively related to corresponding changes in left ventricular mass index ( r=−0.56 , P<0.001 ) and left ventricular hypertrophy index ( r=−0.68 , P<0.001 ) . Conclusions —In marked contrast to the beneficial effect of regular aerobic exercise , several months of resistance training “ reduces ” central arterial compliance in healthy men BACKGROUND Lifestyle modification ( i.e. , regular physical activity and diet ) is effective in preventing the age-related increase in cardiovascular disease risks . Potential therapeutic effects of curcumin ( diferuloylmethane ) have been confirmed on various diseases , including cancer and Alzheimer 's disease , but the effects of curcumin have not been tested on central arterial hemodynamics . The aim of this pilot study was to test the hypothesis that the regular endurance exercise combined with daily curcumin ingestion lowers the age-related increase in left ventricular ( LV ) afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women using a r and omized , double-blind , placebo-controlled , parallel manner . METHODS Forty-five women were r and omly assigned to four interventions : " placebo ingestion " ( n = 11 ) , " curcumin ingestion " ( n = 11 ) , " exercise training with placebo ingestion " ( n = 11 ) , or " exercise training with curcumin ingestion " ( n = 12 ) . Curcumin or placebo pills ( 150 mg/day ) were administered for 8 weeks . Aortic blood pressure ( BP ) and augmentation index ( AIx ) , an index of LV afterload , were evaluated by pulse wave analysis from tonometrically measured radial arterial pressure waveforms . RESULTS There were no significant differences in baseline hemodynamic variables among four groups . After the interventions , brachial systolic BP ( SBP ) significantly decreased in both exercise-trained groups ( P < 0.05 for both ) , whereas aortic SBP significantly decreased only in the combined-treatment ( e.g. , exercise and curcumin ) group ( P < 0.05 ) . Heart rate ( HR ) corrected aortic AIx significantly decreases only in the combined-treatment group . CONCLUSIONS These findings suggest that regular endurance exercise combined with daily curcumin ingestion may reduce LV afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women Purpose Regular physical exercise is recommended for the prevention and treatment of cardiovascular disease . However , it is unclear whether the effects of exercise training on arterial stiffness are the same in older hypertensive individuals as those observed in older healthy subjects . The aim of this study was to compare the effects of exercise training on arterial stiffness between older hypertensive and healthy females . Methods Ninety-two females with untreated hypertension and 108 healthy females were r and omly Output:	Aerobic exercise training significantly ( p < 0.001 ) reduced systolic and diastolic BP in each ethnic group . Sub-analyses suggested somewhat larger reductions in systolic BP following aerobic training in hypertensive Africans compared with hypertensive Asians .
MS21907	*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 effect of the Chignon ankle-foot orthosis on gait versus a st and ard ankle-foot orthosis . Method : A multicentre r and omized study was conducted in seven rehabilitation centres . Hemiplegic patients were recruited after unilateral stroke lasting less than six months . Exclusion criteria were : impossibility to st and for 10 seconds ; ankle passive dorsiflexion < 5 degrees with knee flexed to 90 degrees ; triceps spasticity ≥3/4 on the Ashworth modified scale ; diseases that might impair active participation in the study . Thirteen patients were r and omized to the Chignon group and 15 to the control group . Included patients were given a st and ard ankle-foot orthosis or Chignon ankle-foot orthosis . The Chignon ankle-foot orthosis is an articulated double-stopped custom-made orthosis with elements to assist dorsiflexion and plantar flexion . Gait speed improvement ( ten-metre test ) , kinematic assessment , and functional scales were assessed . Results : Gain ratio of walking speed with the orthosis increased significantly more in the Chignon group than in the control group at day 0 ( 27.2 ± 36 % versus −0.8 ± 17 % ; P = 0.006 ) , day 30 ( 39.9 ± 19 % versus 7.5 ± 17 % ; P = 0.0004 ) and day 90 ( 44.6 ± 27 % versus 17.1 ± 0.3 % ; P = 0.04 ) . There was also a significant improvement in kinematic parameters and spasticity in the Chignon group . Conclusion : Early compensation of distal motor deficiency by the Chignon ankle-foot orthosis improves the immediate gait of hemiplegics more than the st and ard ankle-foot orthosis and seems to modify motor recovery processes in the legs after stroke Objective : To investigate the short- and long-term effects of dynamic ankle foot orthoses on functional ambulation activities in chronic hemiparetic patients . Design : R and omized controlled trial . Setting : University ’s neurological rehabilitation outpatient clinic and orthotics department . Subjects : Twenty-eight chronic hemiparetic patients of level 3–5 according to Functional Ambulation Classification and with a maximum spasticity level of 3 according to Modified Ashworth Scale , were r and omly assigned to the study and control groups . Interventions : The control group ( n = 14 ) was assessed with tennis shoes whereas the study group ( n = 14 ) was assessed initially with tennis shoes and after three months with dynamic ankle foot orthosis . Measures : Functional Reach , Timed Up and Go , Timed Up Stairs , Timed Down Stairs , gait velocity and Physiological Cost Index . Results : In the initial assessment no difference was found between the groups for any of the measured parameters ( P > 0.05 ) . After three months , intergroup comparisons while the patients in the study group were wearing dynamic ankle-foot orthosis showed a significant difference in favour of the study group for Timed Up Stairs 12.00 ( 10.21 ) seconds study versus 15.00 ( 7.29 ) seconds control group ; for gait velocity 0.99 ( 0.45 ) m/s study versus 0.72 ( 0.20 ) m/s control group and for Physiological Cost Index 0.12 ( 0.06 ) beats/min study versus 0.28 ( 0.13 ) beats/min control group ( P < 0.05 ) . No difference was found between the groups for Functional Reach , Timed Up and Go , Timed Down Stairs ( P > 0.05 ) . Conclusion : Chronic hemiparetic patients may benefit from using dynamic ankle-foot orthosis Objective : To examine the effects of an ankle-foot orthosis ( AFO ) on balance performance in patients with hemiparesis of short and long duration . Design : Within-subject r and om order of intervention , cross-sectional study design . Setting s : Medical centres and district hospitals . Subjects : Forty-two subjects with hemiparesis of short duration ( B = six months ) and 61 subjects of long duration ( = 12 months ) . Measurements : The balance and gait ability of subjects were evaluated both with an AFO and without . The static and dynamic balance activities were evaluated by the Balance Master System , whereas the functional balance was assessed with the Berg Balance Scale . The speed and cadence were also measured during a 10-metre walk . Paired t-test was used to determine the effect of the AFO . Results : In subjects with hemiparesis of short duration , we found that subjects wearing an AFO showed significant improvements in ( 1 ) weight-bearing distribution during quiet st and ing ( p / 0.042 , 95 % confidence interval ( CI ) 0.521 , 7.325 ) , ( 2 ) body sway during st and ing on foam surface with eyes open ( p / 0.020 , 95 % CI 0.020 , 0.680 ) and eyes closed ( p / 0.041 , 95 % CI 0.023 , 0.921 ) , ( 3 ) movement velocity during limit of stability test ( LOS ) / toward the affected side ( p / 0.037 , 95 % Cl / 0.978 , / 0.042 ) and nonaffected side ( p / 0.008 , 95 % CI / 2.223 , / 0.377 ) , ( 4 ) maximal excursion toward the affected side ( p / 0.042 , 95 % CI / 19.546,=0.071 ) , and ( 5 ) speed ( p / 0.028 , 95 % CI / 0.204 , / 0.017 ) and cadence ( p / 0.021 , 95 % CI / 22.983 , / 1.864 ) . Such effects were not observed in subjects with hemiparesis of long duration . Conclusions : For the subjects with hemiparesis of short duration , the AFO improves the symmetry in quiet and dynamic st and ing balances . It also increases speed and cadence . However , its effectiveness is minimal for patients of long duration OBJECTIVE To evaluate the kinematic features of rear-foot motion during gait in hemiplegic stroke patients , using anterior ankle-foot orthoses ( AFOs ) , posterior AFOs , and no orthotic assistance . DESIGN Crossover design with r and omization for the interventions . SETTING A rehabilitation center for adults with neurologic disorders . PARTICIPANTS Patients with hemiplegia due to stroke ( n=14 ) and able-bodied subjects ( n=11 ) . INTERVENTIONS Subjects with hemiplegia were measured walking under 3 conditions with r and omized sequences : ( 1 ) with an anterior AFO , ( 2 ) with a posterior AFO , and ( 3 ) without an AFO . Control subjects were measured walking without an AFO to provide a normative reference . MAIN OUTCOME MEASURES Rear-foot kinematic change in the sagittal , coronal , and transverse planes . RESULTS In the sagittal plane , compared with walking with an anterior AFO or without an AFO , the posterior AFO significantly decreased plantar flexion to neutral at initial heel contact ( P=.001 ) and the swing phase ( P<.001 ) , and increased dorsiflexion at the stance phase ( P=.002 ) . In the coronal plane , the anterior AFO significantly increased maximal eversion to neutral ( less inversion ) at the stance phase ( P=.025 ) , and decreased the maximal inversion angle at the swing phase when compared with using no AFO ( P=.005 ) . The posterior AFO also decreased the maximal inversion angle at the swing phase as compared with no AFO ( P=.005 ) . In the transverse plane , when compared with walking without an AFO , the anterior AFO and posterior AFO decreased the adduction angle significantly at initial heel contact ( P=.004 ) . CONCLUSIONS For poststroke hemiplegic gait , the posterior AFO is better than the anterior AFO in enhancing rear-foot dorsiflexion during a whole gait cycle . The anterior AFO decreases rear-foot inversion in both the stance and swing phases , and the posterior AFO decreases the rear-foot inversion in the swing phase when compared with using no AFO BACKGROUND Ankle-foot orthoses are often provided to improve walking in stroke patients , although the evidence of effects on walking and balance control is still inconsistent . This could be caused by a lack of insight into the influence of orthoses on the underlying impairments . These impairments can be assessed with dual plate posturography to determine the relative contribution of each lower limb to balance control and weight-bearing . This study examined the effects of ankle-foot orthoses on functional balance , static and dynamic weight-bearing asymmetry and dynamic balance control of the paretic and non-paretic lower limbs . METHODS Twenty stroke subjects ( time since stroke 5 - 127 months ) completed the study . Subjects were assessed with and without ankle-foot orthosis . Functional balance was assessed using the Berg Balance Scale , Timed Up & Go test , Timed Balance Test , 10-m walking test and Functional Ambulation Categories . Weight-bearing asymmetry and dynamic balance control were assessed with force plates on a movable platform . FINDINGS No significant effects of ankle-foot orthoses were found for weight-bearing asymmetry and dynamic balance control , but significant differences in favour of ankle-foot orthosis use were found for most functional tests . INTERPRETATION Although ankle-foot orthoses had no effect on weight-bearing asymmetry or dynamic balance contribution of the paretic lower limb , functional tests were performed significantly better with orthoses . Apparently , improvements at functional level can not be readily attributed to a greater contribution of the paretic lower limb to weight-bearing or balance control . This finding suggests that ankle-foot orthoses influence compensatory mechanisms Objective : Regaining walking ability is a major goal during the rehabilitation of stroke patients . To support this process an ankle-foot orthosis ( AFO ) is often prescribed . The aim of this study is to investigate the effect of an AFO on walking ability in chronic stroke patients . Design : Cross-over design with r and omization for the interventions . Methods : Twenty chronic stroke patients , wearing an AFO for at least six months , were included . Walking ability was operationalized as comfortable walking speed , scores on the timed up and go ( TUG ) test and stairs test . Patients were measured with and without their AFO , the sequence of which was r and omized . Additionally , subjective impressions of self-confidence and difficulty of the tasks were scored . Clinical ly relevant differences based on literature were defined for walking speed ( 20 cm/s ) , the TUG test ( 10 s ) . Gathered data were statistically analysed using a paired t-test . Results : The mean difference in favour of the AFO in walking speed was 4.8 cm/s ( 95 % CI 0.85–8.7 ) , in the TUG test 3.6 s ( 95 % CI 2.4 4.8 ) and in the stairs test 8.6 s ( 95 % CI 3.1 –14.1 ) . Sixty-five per cent of the patients experienced less difficulty and 70 % of the patients felt more self-confident while wearing the AFO . Conclusions : The effect of an AFO on walking ability is statistically significant , but compared with the a priori defined differences it is too small to be clinical ly relevant . The effect on self-confidence suggests that other factors might play an important role in the motivation to use an AFO Output:	Conclusion ] While the findings suggest the benefits of an AFO regarding gait velocity , the impact of this type of orthosis on cadence remains inconclusive .
MS21908	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The efficacy of Broncho-Vaxom/Imocur ( OM-85 BV ) , an orally administered lyophilized bacterial extract , for recurrent respiratory and ear , nose and throat ( ENT ) infections was evaluated in 116 children aged 6 months to 19 years by comparing its activity in 61 children with that of a placebo in 55 children . The study was r and omized , double-blind , and comprised a 90-day treatment period followed by a 90-day follow-up period without test drugs . Over the 180 days , 39.5 % of patients taking OM-85 BV remained free from infection compared with 16.5 % on placebo ( p less than 0.01 ) . 44 % on OM-85 BV did not need antibiotics compared with 23.5 % on placebo ( p less than 0.05 ) . These differences were even greater in the subgroup of children aged 6 years and less ( 34 vs. 3.5 % for the absence of infections , p less than 0.01 and 37 vs. 10 % for the need of antibiotics , p less than 0.05 ) . Tolerance to OM-85 BV was excellent , and laboratory investigations showed no abnormalities attributable to this product . This work confirms that the immunomodulator OM-85 BV is an effective immunotherapy for recurrent respiratory and ENT infections in children Using a cohort-based design and r and om enrollment , the relation of various risk factors to acute otitis media , respiratory infection and wheezy bronchitis was studied in 2512 children from the fetal period to the age of two years . The complex interrelations of the risk factors with each other were separated out by multivariate analysis , and the confounding effects of antenatal parameters were also st and ardized . Acute otitis media with effusion ( AOME ) , as demonstrated by myringotomy , was analyzed as a specific subgroup of acute otitis media ( AOM ) . Day care in local authority nursery was the major risk factor for both types of acute otitis media . The odds ratio ( OR ) for such children becoming ' otitis-prone ' ( greater than or equal to 3 episodes of AOME ) was 1.8 ( 95 % confidence interval , 1.4 - 2.2 ) . Short duration of breastfeeding involved another significant risk of recurrent respiratory infections and otitis media , the OR for AOME being 1.5 ( 1.1 - 2.0 ) and that for recurrent respiratory infection 1.3 ( 1.1 - 1.6 ) . Allergy and family day care were also significantly associated with infective parameters , but to a lesser extent . The risk factors for wheezy bronchitis were the same as for infections , indicating that wheezy bronchitis is closely related to infections In a 6-month placebo-controlled double-blind multicenter study in 230 patients with recurrent respiratory tract infections , the therapeutic efficacy of Broncho-Vaxom was demonstrated by comparing infection incidence and severity as well as antibacterial medication . Investigators and patients agreed that Broncho-Vaxom exerts a significantly greater protective effect than placebo . Reports of side effects were more frequent with placebo as compared to Broncho-Vaxom BACKGROUND Recurrent acute respiratory tract infections ( RARTIs ) in children are related to IgG subclass deficiencies . The aim of the trial was to evaluate the effect of OM-85 BV in the number of RARTIs as well as in the IgG subclass levels . METHODS This was a r and omized , double-blind , placebo-controlled clinical trial . Patients of ages three to six years , having three or more documented ARTIs during the last six months with subnormal IgG subclass levels were included . Patients took either one capsule of OM-85 BV ( 3.5 mg ) or placebo orally every day for ten consecutive days per month during three consecutive months . Patients were followed three further months without drug intake . IgG subclass levels were determined before and after treatment . RESULTS IgG4 levels diminished after the OM-85 BV treatment ( -3 [ -8.0 , -1.0 ] median difference [ 95 % CI ] p < 0.05 by Wilcoxon test ) . No other significant changes in IgG subclasses were observed . After six months the patients in the OM-85 BV group ( n = 20 ) experienced 2.8 1.4 ( mean SD ) ARTIs , while the patients in the placebo group ( n = 20 ) suffered 5.2 1.5 ARTIs ( -2.4 [ 3.3 , -1.5 ] mean difference [ 95 % CI ] p < 0.001 by Student 's t test ) . Three patients with OM-85 BV had gastrointestinal events related to drug administration , as well as three placebo patients . CONCLUSION This study demonstrated the clinical benefit of OM-85 BV in patients suffering from RARTIs and subnormal levels of IgG subclasses . This trial opens new perspectives in the research of the mechanism of action of OM-85 BV BACKGROUND Acute respiratory tract infections ( ARTIs ) are among the main causes of morbidity and mortality in children . The bacterial extract OM-85 BV has shown some protective effect for ARTIs in preschool children and a reduction in exacerbations of chronic bronchitis in adults . OBJECTIVES This trial reports results of a double-masked , placebo-controlled , parallel-group clinical study that assessed the efficacy and tolerability of OM-85 BV in the prevention of ARTIs in school girls living in an orphanage . METHODS Two hundred girls ( age range , 6 to 13 years ) living in an orphanage entered the trial . Participants were r and omly allocated to receive either OM-85 BV or placebo for 10 consecutive days a month for 3 consecutive months . Patients were followed up for 6 months , including the administration period . The trial began in September 1996 and finished in March 1997 . Primary end points were the type and number of infections . Secondary end points included when an infection occurred , time to clinical cure , severity of infection , absenteeism from school due to an ARTI , number of antibiotics or other drugs prescribed , and duration of concomitant drug treatment . RESULTS During the trial , patients in the OM-85 BV group experienced 143 ARTIs ( 135 upper ARTIs and 8 otitis episodes ) and patients in the placebo group experienced 299 ARTIs ( 273 upper ARTIs , 1 lower ARTI , and 25 otitis episodes ) . The median number of ARTIs was 1.0 ( 0.0 , 3.0 ; 5th percentile , 95th percentile ) in the OM-85 BV group compared with 3.0 ( 2.0 , 4.0 ; 5th percentile , 95th percentile ) in the placebo group . This difference was statistically significant ( P < 0.001 ) . Participants who received OM-85 BV also showed significantly better results ( P < 0.001 ) than participants who received placebo in terms of median duration of illness , median number of missed school days due to an ARTI , median number of antibiotic and drug courses , and median duration of concomitant treatment . There were significant differences ( P < 0.05 ) in severity of ARTIs during month 4 of the trial , with patients receiving OM-85 BV showing less severe ARTIs than patients receiving placebo and shorter mean time to clinical cure from the second month to the fourth month . No adverse events related to the trial medications were reported . CONCLUSIONS OM-85 BV had a preventive effect on ARTIs in the school girls , with a reduction in the antibiotic requirements and the duration of ARTIs . Future studies are needed to further explore the role of OM-85 BV in the prevention of ARTIs The role of repeated infections early in life in the development of childhood asthma and allergies has not been clarified . The aim of this study was to investigate the effect of repeated episodes of fever and antibiotic treatments during the first years of life on the prevalence of asthma , bronchial hyperresponsiveness ( BHR ) , and atopy at school age in a representative population . R and om sample s of schoolchildren aged 5 - 7 yrs ( n=7,545 ) and 9 - 11 yrs ( n=7,498 ) were studied using the International Study of Asthma and Allergies in Childhood ( ISAAC ) phase II protocol . To assess the prevalence of disease and early childhood exposures , parental question naires were administered ( response rates 82.2 % and 85.3 % , respectively ) . In addition , children underwent skin prick tests , hypertonic saline challenge and blood sampling for the measurement of serum immunoglobulin (Ig)E. Repeated episodes of fever and antibiotic treatment in early life were strongly associated with the prevalence of asthma ( odds ratio (OR)=7.95 ; 95 % confidence interval ( CI ) 6.02 - 10.50 ) and current wheeze at school age . Within asthmatic children the number of fever episodes and antibiotic courses were strongly inversely related to the prevalence of atopy ( OR=0.25 ; 95 % CI 0.11 - 0.54 for skin test reactivity ) and BHR ( OR=0.31 ; 95 % CI 0.10 - 0.92 ) . Furthermore , asthmatic children with recurrent early childhood infections were at a lower risk of being symptomatic at school age . When considering atopic and nonatopic asthmatic children separately , the highest risk of asthma with repeated early childhood infections was found for nonatopic asthma ( OR=24.29 ; 95 % Cl 11.86 - 49.76 ) . These findings suggest that a subgroup of children with a triggering or inducing of asthmatic symptoms through repeated early childhood infections exists within the " asthma syndrome " which has a better prognosis and is less related to the atopic phenotype A 6-month double-blind , prospect i ve , r and omized , placebo-controlled trial was conducted to establish the safety and efficacy of OM-85-BV in the treatment of subacute sinusitis and in the following prevention of the respiratory tract infections in 56 children from 18 months to 9 years of age . In the subacute phase of the sinusitis the patients were given one OM-85-BV capsule ( 3.5 mg of bacterial extracts ) ( n = 26 ) or placebo ( n = 30 ) , daily for ten days ; additionally both groups took amoxicillin/clavulanate 40/10 mg/kg daily in three divided doses for 21 days . For the following two months the patients took one OM-85-BV capsule or placebo , ten days a month . In the subacute phase the OM-85-BV group of patients improved sooner ( 5.56 + /- 4.98 vs 10 + /- 8.49 days ) and had a shorter convalescence ( 15.38 + /- 8.91 vs 20.28 + /- 7.17 days ) . During the six month follow-up the patients in the OM-85-BV group had a lower number of infections ( 1.56 + /- 0.3 vs 2.22 + /- 0.43 ) and required a lower number of drug treatments ( 1.47 + /- 0.32 vs 1.94 + /- 0.42 ) . One patient treated with OM-85-BV presented a mild rash which disappeared three days after the drug discontinuation . We conclude that OM-85-BV is safe at pediatric ages , as well as accelerates the cure and improvement of subacute sinusitis while it lowers the incidence of respiratory infections The effect of a bacterial extract orally administered to 20 children with recurrent infections of the upper respiratory tract , was investigated in a double-blind study . The composition of the peripheral blood mononuclear cells ( T and B-lymphocytes , monocytes ) and some of their biochemical properties ( 5'-nucleotidase , beta-N-acetyl-glucosaminidase and non-specific esterase ) were unaffected . In contrast , the allogeneic mixed lymphocyte reaction was significantly increased in patients treated with the bacterial extract . In the treated group the number of infectious episodes decreased significantly and the clinical response correlated positively with the mixed lymphocyte reaction . These findings suggest that the bacterial extract has the capacity of restoring depressed immune functions by acting through the gut-associated lymphoid tissue BACKGROUND Acute respiratory tract infections ( ARTIs ) are among the main causes of morbidity and mortality in children . The bacterial extract OM-85 BV ( bronchovaxom ) has shown protective effect for ARTIs on children . We report a double-blind , placebo-controlled , parallel , prospect i ve clinical trial to assess the safety and efficacy of two courses of OM-85 BV in the prevention of ARTIs in susceptible children during 12 months . METHODS Fifty-four susceptible children from 1 to 12 years of age living in the metropolitan area of Chihuahua City were selected . They were r and omized to receive either OM-85 BV or placebo ( one capsule a day for 10 days a month for 3 consecutive months ) at the beginning of the trial and 6 months later with the same schedule . Patients were followed up for 12 months , including the administration period . Output:	The results of this review were also positive for the active treatment regarding the secondary variables , which were represented by the number of patients with at least one RTI and the mean number of RTIs . Conclusions This meta- analysis shows , as observed in several individual trials , that the population treated with OM-85 BV had significantly and consistently fewer cases of recurrent RTIs . The data suggest that the effect is greater in patients at increased risk of recurrent RTIs
MS21909	*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 Fatigue or lack of interest can reduce the feasibility of intensive physical exercise in nursing home residents . Low-volume exercise interventions with similar training effects might be an alternative . The aim of this r and omised controlled trial was to investigate the feasibility of Whole Body Vibration ( WBV ) in institutionalised elderly , and its impact on functional capacity and muscle performance . Methods Twenty-four nursing home residents ( 15 female , 9 male ; mean age 77.5 ± 11.0 years ) were r and omised ( stratification for age , gender and ADL-category ) to 6 weeks static WBV exercise ( WBV+ , N = 13 ) or control ( only static exercise ; N = 11 ) . Outcome measures were exercise compliance , timed up- and -go , Tinetti-test , back scratch , chair sit- and -reach , h and grip strength and linear isokinetic leg extension . Results At baseline , WBV+ and control groups were similar for all outcome variables . Twenty-one participants completed the program and attended respectively 96 % and 86 % of the exercise sessions for the WBV+ and control groups . Training-induced changes in timed up- and -go and Tinetti-test were better for WBV+ compared to control ( p = 0.029 for timed up- and -go , p = 0.001 and p = 0.002 for Tinetti body balance and total score respectively ) . In an alternative analysis ( Worst Rank Score & Last Observation Carried Forward ) the differences in change remained significant on the Tinetti body balance and total score . No other significant differences in change between both groups were observed . Conclusion In nursing home residents with limited functional dependency , six weeks static WBV exercise is feasible , and is beneficial for balance and mobility . The supplementary benefit of WBV on muscle performance compared to classic exercise remains to be explored further The aims of this r and omised controlled trial were to determine if a high-intensity functional exercise program improves balance , gait ability , and lower-limb strength in older persons dependent in activities of daily living and if an intake of protein-enriched energy supplement immediately after the exercises increases the effects of the training . One hundred and ninety-one older persons dependent in activities of daily living , living in residential care facilities , and with a Mini-Mental State Examination ( MMSE ) score of ? 10 participated . They were r and omised to a high-intensity functional exercise program or a control activity , which included 29 sessions over 3 months , as well as to protein-enriched energy supplement or placebo . Berg Balance Scale , self-paced and maximum gait speed , and one-repetition maximum in lower-limb strength were followed-up at three and six months and analysed by 2 x 2 factorial ANCOVA , using the intention-to-treat principle . At three months , the exercise group had improved significantly in self-paced gait speed compared with the control group ( mean difference 0.04 m/s , p = 0.02 ) . At six months , there were significant improvements favouring the exercise group for Berg Balance Scale ( 1.9 points , p = 0.05 ) , self-paced gait speed ( 0.05 m/s , p = 0.009 ) , and lower-limb strength ( 10.8 kg , p = 0.03 ) . No interaction effects were seen between the exercise and nutrition interventions . In conclusion , a high-intensity functional exercise program has positive long-term effects in balance , gait ability , and lower-limb strength for older persons dependent in activities of daily living . An intake of protein-enriched energy supplement immediately after the exercises does not appear to increase the effects of the training Background : The knowledge concerning balance training actually lowering fall rates among frail older persons is limited . Objective : The aim of this study was to examine the effects of a 4-week individualized visual feedback-based balance training on the fall incidence during 1-year follow-up among frail older women living in residential care . Methods : Twenty-seven older women from 2 residential care homes were r and omized into exercise ( n = 20 ) and control ( n = 7 ) groups . Balance measurements were carried out before and after a 4-week training period and falls were monitored by monthly diaries for 1 year . An interview about fear of falling and physical activity was completed before and after the intervention and after the 1-year follow-up . Results : A positive effect of balance training on fall incidence was found . A dynamic Poisson regression model showed that during the follow-up the monthly risk of falling was decreased in the exercise group compared to controls ( risk ratio 0.398 , 95 % CI 0.174–0.911 , p = 0.029 ) . In addition , the exercise group reported a reduced fear of falling and increased physical activity after a training period but these changes declined during the follow-up period . Conclusion : Individualized visual feedback-based balance training was shown to be a promising method for fall prevention among frail older women . High compliance ( 97.5 % ) with the training program showed that carefully targeted training programs can be carried out among older people with health limitations Background and aims : The level of physical functioning ( PF ) late in life has , in recent years , been shown to be influenced by genetic factors . One of the most extensively studied genetic variants associated with PF and trainability is insertion/deletion ( I/D ) polymorphism in the gene encoding Angiotensin Converting Enzyme ( ACE ) . However , ACE studies have mainly been conducted among younger persons in excellent physical shape . In this study , we examine whether the level of PF , trainability , or rate-of-change are associated with the ACE genotype among the elderly . Methods : We used data from 4 r and omized training studies of elderly Danes ( N=203 ) . The measures of PF were self-report , maximal oxygen uptake , muscle strength , walking speed , and body composition . Results : Overall , a favorable change in the measures of PF was observed in training groups compared with control groups . However , within groups , neither pre- or post-training/control period levels of PF nor differences in pre- and post-levels were associated with the ACE genotype . Conclusions : On the basis of our r and omized studies , we could not detect any association between the ACE genotype and the level of PF or change , regardless of whether response to physical training or spontaneous changes was studied OBJECTIVES To determine the independent and combined effects of progressive resistance muscle strength training ( PRMST ) and megestrol acetate ( MA ) on strength , muscle mass , and function in older recuperative care patients . DESIGN Double-blind , r and omized , controlled intervention using a two-by-two factorial design and conducted between 1999 and 2001 . SETTING University-affiliated Department of Veterans Affairs hospital . PARTICIPANTS Twenty-nine patients ( mean age 79.4 + /- 7.4 , 90 % white ) aged 65 and older and had recent functional decline . INTERVENTIONS After r and omization to one of four treatment groups ( low-resistance exercises plus 800 mg per day of MA or a placebo or high-intensity PRMST plus 800 mg/d of MA or placebo ) , subjects received training and the drug or placebo for 12 weeks . MEASUREMENTS Change in muscle strength , mid-thigh muscle area , and aggregate functional performance score as assessed using analysis of covariance . RESULTS Five subjects withdrew from the study before its completion . Based on intent-to-treat analyses , subjects who received high-intensity PRMST and placebo experienced the greatest strength gains . The addition of MA was associated with worse outcomes than with high-intensity exercise training alone , especially with regard to the leg exercises . Post hoc analysis demonstrated that subjects who received high-intensity PRMST and placebo experienced significantly greater percentage increases in leg strength than subjects in either of the MA treatment groups ( P<.05 for each comparison ) . There was also a significant negative effect of MA on physical function . In general , subjects who received MA experienced a deterioration in aggregate physical function scores , whereas the remaining subjects improved ( -0.80+/-0.40 vs 0.48+/-0.41 , P=.04 ) . There was not a significant interaction between exercise and MA for any outcome . CONCLUSION High-intensity PRMST is a safe and well-tolerated exercise regimen for frail elderly patients . The addition of MA appears to blunt the beneficial effects of PRMST , result ing in less muscle strength and functional performance gains A decline in dietary intake due to inactivity and , consequently , development of a suboptimal nutritional status is a major problem in frail elderly people . However , benefits of micronutrient supplementation , all-round physical exercise or a combination of both on functional biochemical and hematologic indicators of nutritional and health status in frail elderly subjects have not been tested thoroughly . A 17-wk r and omized controlled trial was performed in 145 free-living frail elderly people ( 43 men , 102 women , mean age , 78 + /- 5.7 y ) . Based on a 2 x 2 factorial design , subjects were assigned to one of the following : 1 ) nutrient-dense foods , 2 ) exercise , 3 ) both ( 1 ) and ( 2 ) or 4 ) a control group . Foods were enriched with micronutrients , frequently characterized as deficient [ 25 - 100 % of the recommended daily allowance ( RDA ) ] in elderly people . Exercises focused on skill training , including strength , endurance , coordination and flexibility . Dietary intake , blood vitamin levels and nutritional and health indicators , including (pre)albumin , ferritin , transferrin , C-reactive protein , hemoglobin and lymphocytes were measured . At baseline , 28 % of the total population had an energy intake below 6.3 MJ , up to a maximum of 93 % having vitamin intakes below two thirds of the Dutch RDA . Individual deficiencies in blood at baseline ranged from 3 % for erythrocyte glutathione reductase-alpha to 39 % for 25-hydroxy vitamin D and 42 % for vitamin B-12 . These were corrected after 17 wk in the two groups receiving the nutrient-dense foods , whereas no significant changes were observed in the control or exercise group . Biochemical and hematologic indicators at baseline were within the reference ranges ( mean albumin , 46 g/L ; prealbumin , 0.25 g/L ; hemoglobin , 8.6 mmol/L ) and were not affected by any of the interventions . The long-term protective effects of nutrient supplementation and exercise , by maintaining optimal nutrient levels and thereby reducing the initial chance of developing critical biochemical values , require further investigation . Other indicative functional variables for suboptimal nutritional status , in addition to those currently selected , should also be explored BACKGROUND Frail elders are at risk of suboptimal micronutrient status , functional decline , and neurologic disorders . The influence of oral multimicronutrients in physiologic doses and of moderately intense physical exercise on homocysteine ( Hcy ) , methylmalonic acid ( MMA ) , and neurologic functioning have not yet been investigated . OBJECTIVE Our goal was to determine the effects of enriched foods and exercise on blood vitamins , Hcy , MMA , and neuropsychological functioning in the frail . DESIGN A 17-wk r and omized controlled intervention trial was used to study 1 ) enriched foods plus a social program , 2 ) regular foods plus exercise , 3 ) enriched foods plus exercise , and 4 ) regular foods plus a social program . Enriched foods contained multiple micronutrients ( 25 - 100 % of the Dutch recommended dietary allowances ) ; exercises focused on strength , coordination , flexibility , and endurance . Vitamin ( cobalamin , red blood cell folate , and pyridoxal 5'-phosphate ) , Hcy , and MMA concentrations were measured and 2 neuropsychological tests were conducted . RESULTS Vitamin concentrations were higher in the supplemented groups than in the unsupplemented groups ( P < 0.001 ; total n = 130 ) . Compared with baseline , cobalamin in the supplemented groups was increased by 22 % , plasma folate by 101 % , red blood cell folate by 87 % , and pyridoxal 5'-phosphate by 68 % . Concentrations in the unsupplemented groups changed by -2 % , -6 % , 1 % , and -13 % , respectively . Hcy decreased by 25 % and MMA by 30 % in the supplemented groups , compared with a small increase in Hcy ( 2 % ) and decrease in MMA ( 9 % ) in the unsupplemented groups . Exercise did not significantly affect vitamin , Hcy , or MMA concentrations . No significant effect of either intervention was observed on the neuropsychological tests . CONCLUSIONS The decrease in Hcy and MMA in frail elders confirms a sub clinical metabolic deficiency state . Enriched foods containing physiologic amounts of micronutrients have a beneficial effect on these metabolites . No effects of B vitamins on mental health were identified Fighting against inactivity and inadequate nutritional intake are of utmost importance in the elderly . To our knowledge , the few studies which have been performed were conducted for only a short period and the results do not permit formal conclusions to be drawn . We therefore tried to fill this gap in our knowledge by determining whether an intervention combining an acceptable progressive exercise programme and nutritional supplements would be feasible for a long-term period in the very frail elderly , and would bring about concomitant benefits in body composition and muscle power . Accordingly , this exercise and nutritional combination was assessed in the frail elderly in a 9-month r and omised trial with a factorial design . Fifty-seven elderly volunteers over 72 years , Output:	Emerging evidence suggests that exercise has a positive impact on some physical determinants and on all functional ability outcomes reported in this systematic review . Exercise programs that optimize the health of frail older adults seem to be different from those recommended for healthy older adults . There was a paucity of evidence to characterize the most beneficial exercise program for this population . However , multicomponent training interventions , of long duration ( ≥5 months ) , performed three times per week , for 30 - 45 minutes per session , generally had superior outcomes than other exercise programs . In conclusion , structured exercise training seems to have a positive impact on frail older adults and may be used for the management of frailty
MS21910	*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 effects of a carbohydrate-restricted diet on weight loss and risk factors for atherosclerosis have been incompletely assessed . METHODS We r and omly assigned 132 severely obese subjects ( including 77 blacks and 23 women ) with a mean body-mass index of 43 and a high prevalence of diabetes ( 39 percent ) or the metabolic syndrome ( 43 percent ) to a carbohydrate-restricted ( low-carbohydrate ) diet or a calorie- and fat-restricted ( low-fat ) diet . RESULTS Seventy-nine subjects completed the six-month study . An analysis including all subjects , with the last observation carried forward for those who dropped out , showed that subjects on the low-carbohydrate diet lost more weight than those on the low-fat diet ( mean [ + /-SD ] , -5.8+/-8.6 kg vs. -1.9+/-4.2 kg ; P=0.002 ) and had greater decreases in triglyceride levels ( mean , -20+/-43 percent vs. -4+/-31 percent ; P=0.001 ) , irrespective of the use or nonuse of hypoglycemic or lipid-lowering medications . Insulin sensitivity , measured only in subjects without diabetes , also improved more among subjects on the low-carbohydrate diet ( 6+/-9 percent vs. -3+/-8 percent , P=0.01 ) . The amount of weight lost ( P<0.001 ) and assignment to the low-carbohydrate diet ( P=0.01 ) were independent predictors of improvement in triglyceride levels and insulin sensitivity . CONCLUSIONS Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorie- and fat-restricted diet , with a relative improvement in insulin sensitivity and triglyceride levels , even after adjustment for the amount of weight lost . This finding should be interpreted with caution , given the small magnitude of overall and between-group differences in weight loss in these markedly obese subjects and the short duration of the study . Future studies evaluating long-term cardiovascular outcomes are needed before a carbohydrate-restricted diet can be endorsed BACKGROUND Effective clinical weight management approaches are needed to reach African-Americans . METHODS African-Americans recruited through outpatient practice s for a culturally-adapted Healthy Eating and Lifestyle Program were offered 10 weekly weight loss classes ( Phase 1 ) with the option of continuing for another 8 - 18 months ( Phase 2 ) in a r and omized comparison of further group counseling or staff-facilitated self-help vs. follow-up clinic visits only . RESULTS Of 237 enrollees ( 91 % women ; mean age 43.5 years ; mean body mass index 38.0 kg/m(2 ) ) , 70 [ corrected ] attended no classes or only the first Phase 1 class , 134 provided Phase 1 follow-up data , 128 were r and omized in Phase 2 , and 87 provided final follow-up data ( " completers " ) . Mean weight changes for completers were : -1.5 ( P < 0.001 ) , + 0.3 ( P = 0.47 ) , and -1.2 ( P = 0.04 ) kg , respectively , for Phase 1 , Phase 2 , and overall ( baseline to final visit ; average 18 months total duration ) , with no Phase 2 treatment effect ( P = 0.55 ) . Final study weight was > or = 5 % below baseline for 25 % of completers and was strongly predicted by Phase 1 weight loss . CONCLUSIONS Weight loss achieved in Phase 1 was maintained even with relatively minimal follow-up contact . Increasing the percent who achieve clinical ly significant weight loss initially would improve long-term results OBJECTIVE This study tested the efficacy of an 8-week culturally targeted nutrition and physical activity intervention on body composition . METHODS A r and omized , attention-controlled , two-group trial was conducted in a blackowned commercial gym with a sample of 366 predominantly healthy , obese African American women . A free 1-year membership to the study site gym was provided to participants in both groups . Data were collected at baseline , 2 , 6 , and 12 months . RESULTS Sample retention at 1 year was 71 % . Between-group longitudinal analysis including only participants with complete data revealed a trend toward weight stability in the intervention group at 2 months compared with controls ( + 0.05 kg/m(2 ) , p = 0.75 ; + 0.32 kg/m(2 ) , p = 0.08 , respectively ) , disappearing at 12 months ( + 1.37 kg/m(2 ) , p = 0.0001 ; + 1.02 kg/m(2 ) , p = 0.001 , respectively ) . Within-group analysis demonstrated that intervention and control participants ' fitness ( 1-mile run-walk ) improved by 1.9 minutes ( p = 0.0001 ) and 2.3 minutes ( p = 0.0001 ) , respectively , at 12 months . Mixed model regression analyses demonstrated a significant main effect of the intervention on fitness ( p = 0.0185 ) and a marginally significant effect on body mass index ( BMI ) ( p = 0.057 ) , at 2 months , disappearing by 6 months . By 12 months , however , the controls exhibited a significant advantage in waist circumference stability compared with intervention participants ( + 1.1 cm , p = 0.2763 ; + 2.1 cm , p = 0.0002 , respectively ) . CONCLUSIONS The intervention produced modest short-term improvements in body composition , but the economic incentive of a free 1-year gym membership provided to all participants was a more potent intervention than the education and social support intervention tested . However , longer-term fitness enhancement remains elusive and dem and s research and policy attention . These findings have policy implication s in that employer-/insurer-subsidized gym memberships may require interventions targeting other levels of change ( e.g. , physical or social/environmental ) to foster sustainable fitness improvements A continuing challenge in weight loss treatment is attaining maintenance of weight loss . The goal of this study was to develop a counseling method that would assist African American breast cancer survivors with weight loss maintenance . In this pilot study , 31 obese breast cancer survivors were recruited . Individualized , dietitian-led counseling by telephone and free Weight Watchers coupons were provided to all participants for 18 months . At the 6-month time point , women were r and omized to receive spirituality counseling or not in addition to the st and ard program . The spirituality counseling was delivered via telephone using an 8-step framework . Subjects were asked to utilize daily meditation or prayer , daily readings , and the recording of thoughts in a journal . Mean weight loss from baseline to 6 months was a modest 2.0 % of baseline weight . From 6 to 18 months , there was no further weight change in the spirituality arm and a gain of 0.7 % in the dietitian-only arm . Despite little effect on weight loss , it did appear that spirituality counseling positively affected spiritual well-being ( FACIT-Sp ) scores and dietary quality . The spirituality counseling framework therefore may be further refined and useful for other health promotion studies with African American population BACKGROUND Few studies have examined the weight-control practice s that promote weight loss and weight-loss maintenance in the same sample . PURPOSE To examine whether the weight control practice s associated with weight loss differ from those associated with weight-loss maintenance . METHODS Cross-sectional survey of a r and om sample of 1165 U.S. adults . The adjusted associations of the use of 36 weight-control practice s in the past week with success in weight loss ( ≥10 % lost in the past year ) and success in weight-loss maintenance ( ≥10 % lost and maintained for ≥1 year ) were examined . RESULTS Of the 36 practice s , only 8 ( 22 % ) were associated with both weight loss and weight-loss maintenance . Overall , there was poor agreement ( kappa=0.22 ) between the practice s associated with weight loss and /or weight-loss maintenance . For example , those who reported more often following a consistent exercise routine or eating plenty of low-fat sources of protein were 1.97 ( 95 % CI=1.33 , 2.94 ) and 1.76 ( 95 % CI=1.25 , 2.50 ) times more likely , respectively , to report weight-loss maintenance but not weight loss . Alternatively , those who reported more often doing different kinds of exercises or planning meals ahead of time were 2.56 ( 95 % CI=1.44 , 4.55 ) and 1.68 ( 95 % CI=1.03 , 2.74 ) times more likely , respectively , to report weight loss but not weight-loss maintenance . CONCLUSIONS Successful weight loss and weight-loss maintenance may require two different sets of practice s. Design ing interventions with this premise may inform the design of more effective weight-loss maintenance interventions OBJECTIVE The current study examined ethnic differences in patterns of weight loss and regain in response to an initial behavioral weight loss intervention followed by an extended-care maintenance program . METHODS We analyzed data from 224 women ( African American n = 43 , Caucasian n = 181 ) from rural communities who participated in an initial 6-month lifestyle intervention for obesity and were then r and omized to a face-to-face , telephone , or educational/control extended-care condition . RESULTS African American participants lost less weight during the initial phase of treatment than Caucasian participants ( mean + /- SE = -6.8 + /-.80 vs -10.7 + /- .38 kg , respectively , P = .003 ) . Investigating weight change during month 6 to month 18 , we found a significant interaction between ethnicity and the provision of an extended-care program . Caucasian participants r and omized to either of two extended-care programs regained less weight than those assigned to the control condition ( 1.2 + /- .58 and 4.2 + /- .79 kg , respectively , P=.003 ) , but the provision of extended care did not influence weight regain among African American participants ( 1.9 + /- 1.12 and 1.34 + /- 2.04 kg , respectively , P = .815 ) . CONCLUSION Collectively , these findings suggest that although African American participants lost less weight during the initial phase of treatment , they exhibited better long-term weight-loss maintenance than Caucasian participants . Further , while the provision of extended care successfully enhanced weight maintenance among Caucasian participants , African American participants maintained their initial weight losses regardless of extended care The Hypertension Prevention Trial ( HPT ) was a r and omized , controlled , multicenter ( four clinics , four re source centers ) trial design ed to test the feasibility of achieving and sustaining dietary changes in the intake of calories , sodium , and potassium and to assess the effect of those changes on blood pressure in a normotensive population . The trial involved 841 men and women ( plus a test cohort of 78 ) who , at the first baseline ( BL ) examination , were in the age range of 25 - 49 years and had diastolic blood pressure ( DBP ) greater than or equal to 76 but less than 100 mm Hg ( average of two readings ) , and at the examination prior to r and omization ( BL 2 ) had DBP greater than or equal to 78 but less than 90 mm Hg ( also averaged ) . Participants were r and omly assigned to a control treatment group ( no dietary counseling ) or to one of four dietary treatment groups involving counseling design ed to reduce calorie intake , reduce sodium intake , reduce sodium and calorie intake , and reduce sodium and increase potassium intake . Dietary counseling was provided primarily in group setting s and was aim ed at changing participants ' shopping , cooking , and eating habits related to a design ated treatment assignment . The effect of dietary counseling was measured through changes in urinary excretion of sodium and potassium , changes in body weight , and changes in reported food intake based on 24-hour food records . Blood pressure changes during the 3-year course of followup were based on measurements taken at 6-month intervals from enrollment using a r and om-zero sphygmomanometer . This chapter provides a general description of the design and methods of the HPT and the underlying rationale for decisions affecting the design Objective : Maintaining weight loss is a major challenge in obesity treatment . Individuals often indicate that waning motivation prompts cessation of effective weight management behaviors . Therefore , a novel weight loss maintenance program that specifically targets motivational factors was evaluated . Design : Overweight women ( N=338 ; 19 % African American ) with urinary incontinence were r and omized to lifestyle obesity treatment or control and followed for 18 months . All participants in lifestyle ( N=226 ) received the same initial 6-month group behavioral obesity treatment and were then r and omized to ( 1 ) a novel motivation-focused maintenance program ( N=113 ) or ( 2 ) a st and ard skill-based maintenance approach (N=113).Main Outcome Measure : Weight assessed at baseline , 6 and 18 months . Results : Both treatment groups ( motivation-focused and skill-based ) achieved comparable 18-month weight losses ( −5.48 % for motivation-focused vs −5.55 % in skill-based , P=0.98 ) , and both groups lost significantly more than controls ( −1.51 % ; Output:	The majority of studies failed to describe the specific strategies used in the delivery of the maintenance intervention , adherence to those strategies , and did not incorporate a maintenance phase process evaluation making it difficult to identify intervention characteristics associated with better weight loss maintenance . However , the inclusion of cultural adaptations , particularly in studies with a mixed ethnicity/race sample , result ed in less % weight regain for African American women . Studies with a formal maintenance intervention and weight management as the primary intervention focus reported more positive weight maintenance outcomes for African American women . Nonetheless , our results present both the difficulty in weight loss and maintenance experienced by African American women in behavioral lifestyle interventions
MS21911	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Introduction The pathophysiology of sepsis-associated delirium is not completely understood and the data on cerebral perfusion in sepsis are conflicting . We tested the hypothesis that cerebral perfusion and selected serum markers of inflammation and delirium differ in septic patients with and without sepsis-associated delirium . Methods We investigated 23 adult patients with sepsis , severe sepsis , or septic shock with an extracranial focus of infection and no history of intracranial pathology . Patients were investigated after stabilisation within 48 hours after admission to the intensive care unit . Sepsis-associated delirium was diagnosed using the confusion assessment method for the intensive care unit . Mean arterial pressure ( MAP ) , blood flow velocity ( FV ) in the middle cerebral artery using transcranial Doppler , and cerebral tissue oxygenation using near-infrared spectroscopy were monitored for 1 hour . An index of cerebrovascular autoregulation was calculated from MAP and FV data . C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , S-100β , and cortisol were measured during each data acquisition . Results Data from 16 patients , of whom 12 had sepsis-associated delirium , were analysed . There were no significant correlations or associations between MAP , cerebral blood FV , or tissue oxygenation and sepsis-associated delirium . However , we found a significant association between sepsis-associated delirium and disturbed autoregulation ( P = 0.015 ) . IL-6 did not differ between patients with and without sepsis-associated delirium , but we found a significant association between elevated CRP ( P = 0.008 ) , S-100β ( P = 0.029 ) , and cortisol ( P = 0.011 ) and sepsis-associated delirium . Elevated CRP was significantly correlated with disturbed autoregulation ( Spearman rho = 0.62 , P = 0.010 ) . Conclusion In this small group of patients , cerebral perfusion assessed with transcranial Doppler and near-infrared spectroscopy did not differ between patients with and without sepsis-associated delirium . However , the state of autoregulation differed between the two groups . This may be due to inflammation impeding cerebrovascular endothelial function . Further investigations defining the role of S-100β and cortisol in the diagnosis of sepsis-associated delirium are warranted . Trial registration Clinical Trials.gov NCT00410111 Abstract . Objective : Perfusion abnormalities are an overall phenomenon in severe sepsis and septic shock , leading to organ dysfunction . We investigated whether carbon dioxide (CO2)-induced vasomotor reactivity ( VMR ) is impaired in septic patients , compared with values obtained outside sepsis . Design : Prospect i ve , clinical study . Setting : Six-bed neurologic critical care unit of a university hospital . Patients and participants : Eight consecutive patients with severe sepsis and septic shock . Measurements and results : CO2-reactivity was measured during and outside a period of severe sepsis or septic shock according to ACCP/SCCM criteria by means of transcranial Doppler sonography and near-infrared spectroscopy ( NIRS ) . VMR was calculated as the percentage change of cerebral blood flow velocity ( normalized CO2-reactivity , NCR ) and absolute changes in concentration of oxygenated hemoglobin , deoxygenated hemoglobin , total hemoglobin ( HbO2 , Hb , HbT ) and Hbdiff ( difference between HbO2 and Hb ) in µmol/l per 1 % increase in end-tidal CO2 ( CR-HbO2 , CR-Hb , CR-HbT , CR-Hbdiff ) . NCR and NIRS-reactivities were significantly reduced during severe sepsis and septic shock compared with values outside sepsis ( mean , SD , Wilcoxon ) : NCR 11.0 ( 7.1 ) versus 30.7 ( 13.0 ) , p<0.02 ; CR-HbO2 0.70 ( 0.61 ) versus 2.33 ( 1.11 ) , p<0.02 ; CR-Hb –0.17 ( 0.74 ) versus –1.42 ( 1.28 ) , p<0.04 ; CR-HbT 0.53 ( 0.48 ) versus 1.05 ( 0.40 ) , p<0.03 ; CR-Hbdiff 0.91 ( 1.33 ) versus 3.75 ( 2.33 ) , p<0.02 . This indicates a severely disturbed VMR . Conclusions : In the advent of a disturbed cerebral autoregulation , critical drops in blood pressure during sepsis are transferred directly into the vascular bed , leading to cerebral hypoperfusion . This mechanism might contribute to the pathogenesis of septic encephalopathy Introduction Pathophysiology of brain dysfunction due to sepsis remains poorly understood . Cerebral microcirculatory alterations may play a role ; however , experimental data are scarce . This study sought to investigate whether the cerebral microcirculation is altered in a clinical ly relevant animal model of septic shock . Methods Fifteen anesthetized , invasively monitored , and mechanically ventilated female sheep were allocated to a sham procedure ( n = 5 ) or sepsis ( n = 10 ) , in which peritonitis was induced by intra-abdominal injection of autologous faeces . Animals were observed until spontaneous death or for a maximum of 20 hours . In addition to global hemodynamic assessment , the microcirculation of the cerebral cortex was evaluated using Sidestream Dark-Field ( SDF ) videomicroscopy at baseline , 6 hours , 12 hours and at shock onset . At least five images of 20 seconds each from separate areas were recorded at each time point and stored under a r and om number to be analyzed , using a semi-quantitative method , by an investigator blinded to time and condition . Results All septic animals developed a hyperdynamic state associated with organ dysfunction and , ultimately , septic shock . In the septic animals , there was a progressive decrease in cerebral total perfused vessel density ( from 5.9 ± 0.9 at baseline to 4.8 ± 0.7 n/mm at shock onset , P = 0.009 ) , functional capillary density ( from 2.8 ± 0.4 to 2.1 ± 0.7 n/mm , P = 0.049 ) , the proportion of small perfused vessels ( from 95 ± 3 to 85 ± 8 % , P = 0.02 ) , and the total number of perfused capillaries ( from 22.7 ± 2.7 to 17.5 ± 5.2 n/mm , P = 0.04 ) . There were no significant changes in microcirculatory flow index over time . In sham animals , the cerebral microcirculation was unaltered during the study period . Conclusions In this model of peritonitis , the cerebral microcirculation was impaired during sepsis , with a significant reduction in perfused small vessels at the onset of septic shock . These alterations may play a role in the pathogenesis of septic encephalopathy Introduction The pathophysiology of sepsis-associated encephalopathy ( SAE ) is not entirely clear . One of the possible underlying mechanisms is the alteration of the cerebral microvascular function induced by the systemic inflammation . The aim of the present work was to test whether cerebral vasomotor-reactivity is impaired in patients with SAE . Methods Patients fulfilling the criteria of clinical sepsis and showing disturbance of consciousness of any severity were included ( n = 14 ) . Non-septic persons whithout previous diseases affecting cerebral vasoreactivity served as controls ( n = 20 ) . Transcranial Doppler blood flow velocities were measured at rest and at 5 , 10 , 15 and 20 minutes after intravenous administration of 15 mg/kgBW acetazolamide . The time course of the acetazolamide effect on cerebral blood flow velocity ( cerebrovascular reactivity , CVR ) and the maximal vasodilatory effect of acetazolemide ( cerebrovascular reserve capacity , CRC ) were compared among the groups . Results Absolute blood flow velocities after adminsitration of the vasodilator drug were higher among control subjects than in SAE . Assessment of the time-course of the vasomotor reaction showed that patients with SAE reacted slower to the vasodilatory stimulus than control persons . When assessing the maximal vasodilatory ability of the cerebral arterioles to acetazolamide during vasomotor testing , we found that patients with SAE reacted to a lesser extent to the drug than did control subjects ( CRC controls:46.2 ± 15.9 % , CRC SAE : 31,5 ± 15.8 % , P < 0.01 ) . Conclusions We conclude that cerebrovascular reactivity is impaired in patients with SAE . The clinical significance of this pathophysiological finding has to be assessed in further studies OBJECTIVE To determine whether the severity of septic encephalopathy is correlated with gram-negative bacteremia and mortality and whether there exists a single or combination of metabolic derangements(s ) that cause septic encephalopathy . DESIGN AND SETTING Prospect i ve case series in an academic medical center . PATIENTS Fifty patients selected according to clinical and laboratory criteria for severe sepsis . The criteria included temperature , heart rate , respiratory rate , and hypotension and /or signs of systemic hypoperfusion . MAIN OUTCOME MEASURES A single or combination of metabolic and laboratory derangements and organ failures , three different methods to grade the severity of septic encephalopathy , Acute Physiology and Chronic Health Evaluation II ( APACHE II ) scores , gram-negative bacteremia and infection , and mortality . RESULTS Encephalopathy was associated with an increase in mortality when grade d by the Glasgow Coma Score ; a score of 15 had 16 % mortality , 13 to 14 had 20 % , 9 to 12 had 50 % , and 3 to 8 had 63 % mortality ( P < .05 ) . Bacteremia was associated with encephalopathy ; 13 % of septic patients without encephalopathy vs 59 % of patients with encephalopathy had bacteremia ( P < .001 ) when grade d by altered mental status . Septic encephalopathic patients had elevated serum urea nitrogen and bilirubin levels , increased APACHE II scores , and a higher incidence of renal failure . CONCLUSIONS The severity of septic encephalopathy correlated with mortality , bacteremia , and renal and hepatic dysfunction . The Glasgow Coma Score is a useful tool for characterizing septic encephalopathy . Considerable variations can be found according to different criteria used to classify septic encephalopathy Objective To study the correlation between a dynamic index of cerebral autoregulation assessed with blood flow velocity ( FV ) using transcranial Doppler , and a tissue oxygenation index ( TOI ) recorded with near-infrared spectroscopy ( NIRS ) . Methods Twenty-three patients with sepsis , severe sepsis , or septic shock were monitored daily on up to four consecutive days . FV , TOI , and mean arterial blood pressure ( ABP ) were recorded for 60 min every day . An index of autoregulation ( Mx ) was calculated as the moving correlation coefficient between 10-s averaged values of FV and ABP over moving 5 min time-windows . The index Tox was evaluated as the correlation coefficient between TOI and ABP in the same way . The indices Mx and Tox , ABP and arterial partial pressure of CO2 were averaged for each patient . Results Synchronized slow waves , presenting with periods from 20 s to 2 min , were seen in the TOI and FV of most patients , with a reasonable coherence between the signals in this b and width ( coherence > 0.5 ) . The indices , Mx and Tox , demonstrated good correlation with each other ( R = 0.81 ; P < 0.0001 ) in the whole group of patients . Both indices showed a significant ( P < 0.05 ) tendency to indicate weaker autoregulation in the state of vasodilatation associated with greater values of arterial partial pressure of CO2 or lower values of ABP . Conclusion NIRS shows promise for the continuous assessment of cerebral autoregulation in adults INTRODUCTION The pathophysiology of sepsis-associated encephalopathy ( SAE ) is not entirely clear , but one of the possible underlying mechanisms is the alteration of the cerebral microvascular function . The aim of the present work was to test whether cerebral vasomotor reactivity is impaired in patients with severe sepsis . METHODS Patients fulfilling the criteria of clinical sepsis and showing at least 2 organ dysfunctions were included ( n = 16 ) . Nonseptic healthy persons without previous diseases affecting cerebral vasoreactivity served as controls ( n = 16 ) . Transcranial Doppler blood flow velocities were measured at rest and at 5 , 10 , 15 , and 20 minutes after intravenous administration of 15 mg/kg acetazolamide . The time course of the acetazolamide effect on cerebral blood flow velocity ( cerebrovascular reactivity [ CVR ] ) and the Output:	A temporal pattern of the evolution of the illness was found . In early sepsis , the median blood flow velocity ( Vm ) and pulsatility index ( PI ) increased , and the cerebral autoregulation ( CA ) remained unchanged . In contrast , Vm normalization , PI reduction and CA impairment were found in later sepsis ( patients with severe sepsis or septic shock ) . Cerebral haemodynamic is impaired in sepsis . Modifications in cerebral blood flow may be consequence to the endothelial dysfunction of the microvasculature induced by the release of inflammatory mediators . A better underst and ing of cerebral hemodynamics may improve the clinical management of patients with sepsis and , consequently , improve clinical outcomes
MS21912	*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 federal menu labeling law will require chain restaurants to post caloric information on menus , but the impact of labeling is uncertain . PURPOSE The goal of the current study was to examine the effect of menu labeling on calories purchased , and secondarily , to assess self-reported awareness and use of labels . DESIGN Single-community pre-post-post cross-sectional study . Data were collected in 2008 - 2010 and analyzed in 2011 - 2012 . SETTING / PARTICIPANTS 50 sites from 10 chain restaurants in King County , Washington , selected through stratified , two-stage cluster r and om sampling . A total of 7325 customers participated . Eligibility criteria were : being an English speaker , aged ≥ 14 years , and having an itemized receipt . The study population was 59 % male , 76 % white non-Hispanic , and 53 % aged<40 years . INTERVENTION A regulation requiring chain restaurants to post calorie information on menus or menu boards was implemented . MAIN OUTCOME MEASURES Mean number of calories purchased . RESULTS No significant changes occurred between baseline and 4 - 6 months postregulation . Mean calories per purchase decreased from 908.5 to 870.4 at 18 months post-implementation ( 38 kcal , 95 % CI=-76.9 , 0.8 , p=0.06 ) in food chains and from 154.3 to 132.1 ( 22 kcal , 95 % CI=-35.8 , -8.5 , p=0.002 ) in coffee chains . Calories decreased in taco and coffee chains , but not in burger and s and wich establishments . They decreased more among women than men in coffee chains . Awareness of labels increased from 18.8 % to 61.7 % in food chains and from 4.4 % to 30.0 % in coffee chains ( both p<0.001 ) . Among customers seeing calorie information , the proportion using it ( about one third ) did not change substantially over time . After implementation , food chain customers using information purchased on average fewer calories compared to those seeing but not using ( difference=143.2 kcal , p<0.001 ) and those not seeing ( difference=135.5 kcal , p<0.001 ) such information . CONCLUSIONS Mean calories per purchase decreased 18 months after implementation of menu labeling in some restaurant chains and among women but not men This study investigated the effectiveness of labeling foods with the Choices nutrition logo on influencing cafeteria menu selection and the behavioral determinants of menu choices in work site cafeterias in the Netherl and s. A cluster r and omized controlled trial was conducted . Intervention cafeterias ( n=13 ) , where the Choices logo was used to promote healthier eating for a 3-week period , were compared with control cafeterias ( n=12 ) , which offered the same menu without the logo . Sales data were collected daily for 9 weeks , from March to May 2009 . In addition , employees from one intervention and one control company completed an online question naire at baseline and after the intervention ( n=368 ) in which the behavioral determinants of food choice ( ie , attitude , self-efficacy , and intention ) and logo use were measured . Generalized estimating equation analyses , χ² tests , t tests and linear regression analyses were performed . No nutritionally meaningful intervention effects were found in the sales of s and wiches , soups , snacks , fruit , and salads . Also , no significant differences in behavioral determinants were found . " Intention to eat healthier " and " paying attention to product information " were positively associated with self-reported consumption of foods with the Choices logo at lunch . The intervention did not have a significant effect on employees ' lunchtime food choices . Labeling healthy choices might be useful for health-conscious employees in the volitional phase of behavior change . Further research should focus on the possible health benefits of menu reformulation in the catering sector Objective Obesity is a pressing public health problem without proven population -wide solutions . Research ers sought to determine whether a city-m and ated policy requiring calorie labeling at fast food restaurants was associated with consumer awareness of labels , calories purchased and fast food restaurant visits . Design and Methods Difference-in-differences design , with data collected from consumers outside fast food restaurants and via a r and om digit dial telephone survey , before ( December 2009 ) and after ( June 2010 ) labeling in Philadelphia ( which implemented m and atory labeling ) and Baltimore ( matched comparison city ) . Measures included : self-reported use of calorie information , calories purchased determined via fast food receipts , and self-reported weekly fast-food visits . Results The consumer sample was predominantly Black ( 71 % ) , and high school educated ( 62 % ) . Post-labeling , 38 % of Philadelphia consumers noticed the calorie labels for a 33 percentage point ( p<.001 ) increase relative to Baltimore . Calories purchased and number of fast food visits did not change in either city over time . Conclusions While some consumer reports noticing and using calorie information , no population level changes were noted in calories purchased or fast food visits . Other controlled studies are needed to examine the longer term impact of labeling as it becomes national law The increase in the weight of American adults and children has been positively associated with the prevalence of the consumption of food-away-from-home . The objective was to assess the accuracy of cl aim ed nutritional information of foods purchased in contracted foodservices located on the campus of an institution of higher education . Fifty popular food items were r and omly collected from five main dining outlets located on a selected campus in the northeastern United States . The sampling was repeated three times on separate occasions for an aggregate total of 150 food sample s. The sample s were then weighed and assessed for nutrient composition ( protein , cholesterol , fiber , carbohydrates , total fat , calories , sugar , and sodium ) using nutrient analysis software . Results were compared with foodservices ' published nutrition information . Two group comparisons , cl aim ed and measured , were performed using the paired- sample t-test . Descriptive statistics were used as well . Among the nine nutritional values , six nutrients ( total fat , sodium , protein , fiber , cholesterol , and weight ) had more than 10 % positive average discrepancies between measured and cl aim ed values . Statistical significance of the variance was obtained in four of the eight categories of nutrient content : total fat , sodium , protein , and cholesterol ( P < .05 ) . Significance was also reached in the variance of actual portion weight compared to the published cl aims ( P < .001 ) . Significant differences of portion size ( weight ) , total fat , sodium , protein , and cholesterol were found among the sample d values and the foodservices ' published cl aims . The findings from this study raise the concern that if the actual nutritional information does not accurately reflect the declared values on menus , conclusions , decisions and actions based on posted information may not be valid We surveyed 7318 customers from 275 r and omly selected restaurants of 11 fast food chains . Participants purchased a mean of 827 calories , with 34 % purchasing 1000 calories or more . Unlike other chains , Subway posted calorie information at point of purchase and its patrons more often reported seeing calorie information than patrons of other chains ( 32 % vs 4 % ; P<.001 ) ; Subway patrons who saw calorie information purchased 52 fewer calories than did other Subway patrons ( P<.01 ) . Fast-food chains should display calorie information prominently at point of purchase , where it can be seen and used to inform purchases OBJECTIVE The present study is to describe , on the basis of recent Finnish population surveys , ( i ) the frequencies of school and worksite canteen use , ( ii ) the determinants of having a hot lunch during school or working hours and ( iii ) the associations of lunch eating patterns with food habits . SETTING The study summarises mainly basic reports and studies concerning catering services conducted in Finl and based on nationally representative population surveys . Design and subjectsCross-sectional study . The most important surveys cited in this paper are the School Health Promotion Study , the Work and the Working Conditions survey , the National FINDIET 2002 Study , and the Health Behavior and Health among Finnish Adult Population survey . RESULTS School lunch is eaten by on average 70 - 90 % of children aged 9 - 18 years . Of all employees , 30 % eat at a worksite canteen daily , whereas 30 % of men and 45 % of women eat packed lunches . Nationally representative cross-sectional population surveys show that the use of catering services is associated with more healthy food habits ; schoolchildren eating school meals and employees eating lunch at a worksite canteen tend to make food choices closer to nutritional recommendations as compared to those not using catering services to the same degree . CONCLUSIONS Some evidence exists that catering services in schools and worksites contribute to healthy eating habits in the population . In order to verify the positive role of catering services more scientific research with prospect i ve and intervention design studies will be needed OBJECTIVE To examine the influences of nutritional information and consumer characteristics on meal quality expectations , food selection and subsequent macronutrient intakes of consumers offered a reduced-fat option in a restaurant . DESIGN A target , full-fat ( FF ) main restaurant meal option was developed in a version substantially reduced in fat and energy ( RF ) . Restaurant patrons were r and omly placed into one of four treatment groups varying in provision of menu information about the target dish , and the actual version of that dish served ( if ordered ) . A full-fat blind ( FFB ) control group was given no nutritional information in the menu and was served the FF version . The other three groups were all served the modified RF version : ( i ) reduced-fat blind ( RFB ) , who were given no nutritional information ; ( ii ) reduced-fat informed ( RFI ) , who were given nutritional information ; and ( iii ) reduced-fat informed with details ( RFID ) , who were given the same nutritional information plus recipe modification details . Subjects rated their expected and actual liking , the pleasantness of taste , texture and appearance of the dish , how well the dish matched their expectations , and the likelihood of purchase again . Additional measures included the other dish selection s , sociodemographic and attitudinal information . SETTING A silver service ( training ) restaurant . SUBJECTS Members of the public ( n = 279 ) consuming meals in the restaurant . RESULTS The presence of nutritional information on the menu did not significantly increase subsequent intakes of energy and fat from the rest of the meal , and did not significantly influence sensory expectations or post-meal acceptance measures ( which also did not differ between the FF and RF versions ) . Consumer characteristics relating to fat reduction attitudes and behaviours were significantly related to the selection of different dishes . CONCLUSIONS Provision of RF alternatives in a restaurant can have significant positive dietary benefits . Menu nutritional information did not affect measures of meal acceptance . Further studies should identify which types of information formats might be most effective in enhancing the selection of ' healthy ' options This study assessed whether the inclusion of kilojoule labelling alone or accompanied by further nutrition information on menus led adults to select less energy-dense fast food meals . A between-subjects experimental design was used with online menu boards systematic ally varied to test the following labelling conditions : none ( control ) ; kilojoule ; kilojoule+percent daily intake ; kilojoule+traffic light ; and kilojoule+traffic light+percent daily intake . Respondents were 1294 adults aged 18 - 49 in Victoria , Australia who had purchased fast food in the last month and were r and omly assigned to conditions . Respondents in the no labelling condition selected meals with the highest mean energy content and those viewing the kilojoule and kilojoule+traffic light information selected meals with a significantly lower mean energy content , that constituted a reduction of around 500kJ ( 120kcal ) . Respondents most commonly reported using the traffic light labels in making their selection s. These findings provide support for the policy of disclosure of energy content on menus at restaurant chains . Given the magnitude of the reduction in energy density reported , and the prevalence of fast food consumption , this policy initiative has the potential to yield health benefits at the population level CONTEXT National recommendations for the prevention and treatment of obesity emphasize reducing energy intake . Foods purchased in restaurants provide approximately 35 % of the daily energy intake in US individuals but the accuracy of the energy contents listed for these foods is unknown . OBJECTIVE To examine the accuracy of stated energy contents of foods purchased in restaurants . DESIGN AND SETTING A vali date d bomb calorimetry technique was used to measure dietary energy in food from 42 restaurants , comprising 269 total food items and 242 unique foods . The restaurants and foods were r and omly selected from quick-serve and sit-down restaurants in Massachusetts , Arkansas , and Indiana between January and June 2010 . MAIN OUTCOME MEASURE The difference between restaurant-stated and laboratory-measured energy contents , which were corrected for st and ard metabolizable energy conversion factors . RESULTS The absolute stated energy contents were not significantly different from the absolute measured energy contents overall ( difference of 10 kcal/portion ; 95 % confidence interval [ CI ] , -15 to 34 kcal/portion ; P = .52 ) ; however , the stated energy contents of individual foods were variable relative to the measured energy contents . Of the 269 food items , 50 ( 19 % ) contained measured energy contents of at least 100 kcal/portion more than the stated energy contents . Of the 10 % of foods with the highest excess energy in the initial sampling , 13 of 17 were available for a second sampling . In the first analysis , these foods contained average measured energy contents of 289 kcal/portion ( 95 % CI , 186 to 392 kcal/portion ) more than the stated energy contents Output:	DATA ANALYSIS The results were mixed , but a partial influence of menu labeling on food choices was more frequent than an overall influence or no influence . Menu labeling was more effective in cafeterias than in restaurants . Qualitative information , such as healthy-food symbols and traffic-light labeling , was most effective in promoting healthy eating . Calorie labeling in menus is not effective to promote healthier food choices .
MS21913	*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 long-term complications of immunosuppressive therapy such as diabetes , hypercholesterolemia , and hypertension are a major source of morbidity in liver transplant recipients . In this prospect i ve , r and omized , open-label study we completely withdrew prednisone ( PRED ) 14 days after liver transplantation in an effort to decrease these metabolic complications . Patients were maintained on mycophenolate mofetil ( MMF ) in combination with either cyclosporine ( CsA ; Neoral formulation ) or tacrolimus ( TAC ) . Thus , we also were able to compare CsA to TAC in patients not receiving PRED with respect to efficacy , toxicity , and effect on posttransplant metabolic complications . METHODS A total of 71 patients were r and omized to receive either TAC-MMF ( n=35 ) or CsA-MMF ( n=36 ) after liver transplantation and were analyzed for patient and graft survival . Fifty-eight patients continued the immunosuppressive protocol for at least 6 months after transplantation and were analyzed for the incidence of acute rejection and the prevalence of diabetes , hypertension , and hypercholesterolemia . RESULTS The 6-month patient survival rates were 94.4 % for CsA-MMF and 88.6 % for TAC-MMF . Corresponding 6-month graft survival rates were 88.7 % and 85.71 % with no immunologic graft losses in either group . The incidence of biopsy-proven acute rejection was 46 % for CsA-MMF and 42.3 % for TAC-MMF . Six patients were converted from CsA to TAC ( four for recurrent rejection ) and seven patients were converted from TAC to CsA ( four for neurotoxicity ) . Only one patient ( in the TAC-MMF group ) developed new-onset posttransplant diabetes . In contrast , four of eight patients in the CsA-MMF group who were diabetic before transplant became nondiabetic in the first 3 months after transplant . The mean serum cholesterol level was significantly lower in the TAC-MMF group than in the CsA-MMF group ( 145.2+/-41.8 mg/dl and 190.3+/-62.2 , respectively ; P<0.001 ) and the incidence of hypertension was lower in the TAC-MMF group ( 12 % vs. 30.3 % in the CsA-MMF group , P<0.01 ) . Both groups had a lower incidence of metabolic complications compared with a historical group ( n=100 ) maintained on CsA and PRED ( 10 mg/day at 6 months ) . CONCLUSIONS MMF in combination with either TAC or CsA allows withdrawal of PRED 14 days after liver transplantation with a moderate rejection rate and no immunologic graft losses . Early PRED withdrawal decreases posttransplant diabetes , hypercholesterolemia , and hypertension , but patients maintained on TAC have lower serum cholesterol levels and a lower incidence of hypertension than CsA-treated patients BACKGROUND Results of studies in adult recipients of liver allograft suggest that tacrolimus is more efficacious than ciclosporin microemulsion in the prevention of acute rejection . We aim ed to compare these drugs in children undergoing liver transplantation . METHODS This 12-month multicentre , open-label , parallel-group , r and omised study compared a dual tacrolimus regimen ( tacrolimus/corticosteroids , n=93 ) with a triple ciclosporin microemulsion regimen ( ciclosporin microemulsion/corticosteroids/azathioprine , n=92 ) in children who had had liver transplants ( age < or = 16 years , bodyweight < or = 40 kg ) . Initial oral daily doses were 0.30 mg/kg for tacrolimus and 10 mg/kg for ciclosporin microemulsion . Primary endpoint was the incidence of and time to first histologically proven acute rejection . We excluded patients from analysis if they did not receive the study drug , or were given incorrect medication . Otherwise patients were analysed in accordance with their r and om treatment allocation , irrespective of whether they switched medication during the trial . FINDINGS Median age was 22 months ( IQR 9 - 56 ) in the tacrolimus group and 17 months ( 9 - 54 ) in the ciclosporin microemulsion group . We noted no difference between treatment groups with respect to patient survival ( 93.4 % vs 92.2 % ; p=0.77 ) or graft survival ( 92.3 % vs 85.4 % ; p=0.16 ) at month 12 after transplant . The acute rejection free rate at study end ( Kaplan-Meier method ) was 55.5 % for patients on tacrolimus and 40.2 % for patients on ciclosporin microemulsion ( p=0.0288 ) . The Kaplan-Meier estimate of patients free from corticosteroid-resistant acute rejection at study end was 94.0 % for tacrolimus-treated patients and 70.4 % for ciclosporin-microemulsion-treated patients ( p<0.0001 ) . Overall , incidence of adverse events did not differ between groups . INTERPRETATION Tacrolimus is a safe and effective treatment for the prevention of rejection after liver transplantation in children OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials BACKGROUND Calcineurin inhibitors are the most commonly used immunosuppressive drugs in liver transplantation , but the optimum initial immunosuppression regimen is not known . The aim of our study was to compare tacrolimus with microemulsified ciclosporin , in a regimen with st and ardised concomitant immunosuppressive therapy . METHODS In all liver transplant centres in the UK and Republic of Irel and , 606 patients undergoing a first orthotopic liver transplantation were r and omly assigned open-label tacrolimus or microemulsified ciclosporin . Primary outcome was the combined frequency ( whichever occurred first ) of death , retransplantation , or treatment failure for immunological reasons , analysed by intention to treat . FINDINGS 96 % of patients received the treatment allocated to them . The primary outcome was reached in 62 ( 21 % ) of 301 patients in the tacrolimus group versus 99 ( 32 % ) of 305 allocated microemulsified ciclosporin ( relative risk 0.63 [ 95 % CI 0.48 - 0.84 ] , p=0.001 ; time-to-event analysis log-rank test p=0.002 ) : deaths ( 50 [ 17 % ] vs 72 [ 24 % ] ) ; retransplantations ( 11 [ 4 % ] vs 31 [ 10 % ] ) treatment failure for immunological reasons ( 6 [ 2 % ] vs 12 [ 4 % ] ) . The relative risk for the composite outcome was in favour of tacrolimus . The main causes of death in both trial groups were sepsis and multiple organ failure ( 31 [ 10 % ] vs 30 [ 10 % ] ) , and the main cause for retransplantation was hepatic artery thrombosis ( 6 [ 2 % ] vs 17 [ 6 % ] ) . Renal dysfunction and the need for antihypertensive therapy were much the same in both groups . Tacrolimus was more diabetogenic . INTERPRETATION Clinical outcome at 1 year was better with tacrolimus-based immunosuppression than with microemulsified ciclosporin during the first year after liver transplantation . Tacrolimus should be the first choice of calcineurin inhibitor for patients receiving their first liver graft Abstract : Background : This is a 4‐yr follow‐up of a trial using mycophenolate mofetil ( MMF ) induction in orthotopic liver transplantation ( OLT ) . The goal of this study was to evaluate a multidrug approach that would reduce both early and long‐term morbidity related to immunosuppression while maintaining an acceptable freedom from rejection BACKGROUND Immunosuppression in patients with hepatitis C virus ( HCV ) following orthotopic liver transplantation can lead to significant increases in serum viral loads . Our aim was to analyze the effect of a r and omized study of two immunosuppressive agents ( tacrolimus vs. microemulsion cyclosporine ) on the outcome of HCV patients following orthotopic liver transplantation . METHODS From December 1995 to September 1996 , 50 adult patients transplanted for HCV cirrhosis were r and omly assigned to receive tacrolimus ( Prograf ) ( group 1 , 25 patients ) or microemulsion cyclosporine ( Neoral ) ( group 2 , 24 patients ) . All patients received alpha-interferon after transplantation , and the overall steroid doses were no different between the groups . Serum RNA levels were measured by signal amplification of Chiron . Biopsies were taken when transaminases were greater than 2x base line or when there was an inappropriate response to alterations in immunosuppression regimens . RESULTS There were more episodes of rejection in the Neoral group , but there were no differences in bacterial and viral infections , nor in the rate of HCV recurrence between the two groups . There were seven deaths in group 1 and eight in group 2 . Overall patient and graft survival rates in the Prograf and Neoral groups at 18 months were 72 and 68 % and 67 and 64 % , respectively . CONCLUSIONS ( a ) Both immunosuppression regimens had similar HCV recurrence rates ; ( b ) there were no differences in bacterial or opportunistic infections ; and ( c ) patient and graft survival was similar between the two groups Hepatitis C virus (HCV)-induced cirrhosis is the commonest indication for orthotopic liver transplantation , but HCV recurrence is nearly universal and may worsen patient / graft outcomes . The frequency and severity of HCV recurrence has apparently increased in recent years , raising concern about a possible role for newer immunosuppression regimens in this increase , including potentially tacrolimus . We r and omized 79 patients to receive tacrolimus or cyclosporine as primary immunosuppressant posttransplantation . A pathologist blinded to treatment review ed serial liver biopsies . Month 12 cumulative probabilities of histological hepatitis C recurrence for tacrolimus- and cyclosporine-treated patients were .38 and .54 ( P = .19 ) and failure / death were .25 and .28 , respectively ( P = .789 ) . Although cyclosporine-treated patients had significantly larger increases in median serum HCV RNA levels ( months 1 , 6 , and 12 ) , no significant differences were observed between the two treatment arms in histologically-diagnosed HCV recurrence / survival rates . In conclusion , choice of calcineurin inhibitors does not impact severity of recurrent HCV BACKGROUND Many reports of successful early withdrawal of regular maintenance steroids in transplant recipients have appeared in recent years . The question now arises whether , in the current age of powerful nonsteroidal immunosuppressants such as Neoral and Tacrolimus , routine administration of steroids posttransplant is necessary at all . This single center pilot study reports on the feasibility , safety , and efficacy of single agent immunosuppression " ab initio " with either Neoral or Tacrolimus , and no routine or maintenance steroids . METHODS A total of 64 adult patients receiving first liver grafts for a variety of indications were r and omized to receive either Neoral 5 mg/kg BDS or Tacrolimus 0.05 mg/kg BDS orally . Liver biopsies were performed on postoperative days 5 and 10 , and whenever else clinical ly indicated . Rejection episodes were treated with 1.0 g of Methylprednisolone daily for 3 consecutive days . A further episode of rejection after two courses Output:	Tacrolimus is superior to cyclosporin in improving survival ( patient and graft ) and preventing acute rejection after liver transplantation , but it increases the risk of post-transplant diabetes .
MS21914	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES To examine the safety and efficacy of ombitasvir and ABT-450 with ritonavir ( ABT-450/r ) ± ribavirin ( RBV ) in treatment-naïve , non-cirrhotic adults with chronic HCV genotype 1 - 3 infection . METHODS Patients in this open-label , exploratory , phase 2 , multicenter study received ombitasvir ( 25 mg QD ) and ABT-450/r ( 200/100 mg QD ) ± RBV for 12 weeks . Primary efficacy endpoint was HCV RNA < lower limit of quantitation ( LLOQ ) from week 4 through 12 . Sustained virologic response 12 weeks post-treatment ( SVR12 ) was a secondary endpoint . RESULTS Sixty-one patients were enrolled . Among genotype 1- , 2- , and 3-infected patients , respectively , HCV RNA was < LLOQ from week 4 through 12 in 10 ( 100 % ; 95 % CI 69 - 100 ) , 9 ( 90 % ; 56 - 100 ) , and 7 ( 70 % ; 35 - 93 ) receiving the RBV-containing regimen and 9 ( 90 % ; 56 - 100 ) , 8 ( 80 % ; 44 - 97 ) , and 2 ( 18 % ; 2 - 52 ) receiving the RBV-free regimen . Among genotype 1- , 2- , and 3-infected patients , respectively , SVR12 was achieved by 10 ( 100 % ) , 8 ( 80 % ) , and 5 ( 50 % ) receiving the RBV-containing regimen , and 6 ( 60 % ) , 6 ( 60 % ) , and 1 ( 9 % ) receiving the RBV-free regimen . The most common adverse events were fatigue , nausea , and headache . One patient discontinued due to an adverse event . CONCLUSIONS In this study , ombitasvir and ABT-450/r ± RBV regimens were generally well-tolerated . Sustained virologic response was achieved in most patients with HCV genotype 1 or 2 infection , but low SVR rates were observed in HCV genotype 3-infected patients BACKGROUND Sofosbuvir ( SOF ) is active against all hepatitis C virus ( HCV ) genotypes , and SOF-based therapies lead to high rates of sustained virologic response ( SVR ) . However , genotype 3 ( GT3 ) HCV remains a challenge with lower SVR rates reported , particularly in patients with cirrhosis . This study reports the effectiveness and safety of SOF-based therapy in patients with GT3 HCV treated in clinical practice . METHODS Hepatitis C Virus Therapeutic Registry and Research Network is an international , prospect i ve observational study evaluating patients treated in usual clinical practice . Patients with GT3 HCV were analyzed to assess predictors of treatment response and adverse events using descriptive statistics and multivariable logistic regression . RESULTS Treatment outcomes were available for 197 patients treated with SOF and ribavirin ( RBV ) , with or without peginterferon , including 54 % with cirrhosis and 49 % who failed prior therapy . Of 178 patients treated with SOF/RBV , 60 % achieved SVR at 12 weeks ( SVR12 ) , compared with 84 % of 19 patients treated with SOF/peginterferon/RBV . For patients treated with SOF/RBV , the SVR12 rate was 58 % in treatment-naive patients with cirrhosis , and 42 % in those with cirrhosis who failed prior therapy . In noncirrhotic patients , SVR12 rates were 89 % in treatment-naive and 88 % in treatment-experienced patients . After controlling for age and sex , absence of cirrhosis ( odds ratio [ OR ] , 6.4 ; 95 % confidence interval [ CI ] , 2.78 - 14.74 ) , albumin levels ≥3.2 g/dL ( OR , 12.48 ; 95 % CI , 3.86 - 40.33 ) , and platelet count > 10(5 ) cells/µL ( OR , 7.44 ; 95 % CI , 3.51 - 15.78 ) were associated with greater odds of SVR12 CONCLUSIONS : SVR rates were acceptable in patients with GT3 HCV without cirrhosis ; however , in those with cirrhosis , treatment with SOF/RBV was suboptimal , highlighting the need for new therapies for this population Treatment options for patients with hepatitis C virus ( HCV ) genotype 3 infection are limited , with the currently approved all-oral regimens requiring 24-week treatment and the addition of ribavirin ( RBV ) . This phase III study ( ALLY-3 ; http:// Clinical Trials.gov : NCT02032901 ) evaluated the 12-week regimen of daclatasvir ( DCV ; pangenotypic nonstructural protein [NS]5A inhibitor ) plus sofosbuvir ( SOF ; pangenotypic NS5B inhibitor ) in patients infected with genotype 3 . Patients were either treatment naïve ( n = 101 ) or treatment experienced ( n = 51 ) and received DCV 60 mg plus SOF 400 mg once-daily for 12 weeks . Co primary endpoints were the proportions of treatment-naïve and treatment-experienced patients achieving a sustained virological response ( SVR ) at post-treatment week 12 ( SVR12 ) . SVR12 rates were 90 % ( 91 of 101 ) and 86 % ( 44 of 51 ) in treatment-naïve and treatment-experienced patients , respectively ; no virological breakthrough was observed , and ≥99 % of patients had a virological response ( VR ) at the end of treatment . SVR12 rates were higher in patients without cirrhosis ( 96 % ; 105 of 109 ) than in those with cirrhosis ( 63 % ; 20 of 32 ) . Five of seven patients who previously failed treatment with an SOF-containing regimen and 2 of 2 who previously failed treatment with an alisporivir-containing regimen achieved SVR12 . Baseline characteristics , including gender , age , HCV-RNA levels , and interleukin-28B genotype , did not impact virological outcome . DCV plus SOF was well tolerated ; there were no adverse events ( AEs ) leading to discontinuation and only 1 serious AE on-treatment , which was unrelated to study medications . The few treatment-emergent grade 3/4 laboratory abnormalities that were observed were transient . Conclusion : A 12-week regimen of DCV plus SOF achieved SVR12 in 96 % of patients with genotype 3 infection without cirrhosis and was well tolerated . Additional evaluation to optimize efficacy in genotype 3–infected patients with cirrhosis is underway . ( Hepatology 2015;61:1127–1135 Abstract Background & Aims ABT‐530 is a next‐generation hepatitis C virus ( HCV ) NS5A inhibitor with potent pangenotypic antiviral activity in vitro . Paritaprevir is an NS3/4A protease inhibitor codosed with ritonavir that displays in vitro activity against HCV genotypes 1–4 and 6 . Methods Efficacy , pharmacokinetics and safety of ABT‐530 with paritaprevir/ritonavir and ribavirin were evaluated in this phase 2 , open‐label , multicentre study in treatment‐naïve non‐cirrhotic patients with genotype 3 infection . Ten patients , all genotype 3a , received 120 mg ABT‐530 and 150/100 mg paritaprevir/ritonavir once daily with ribavirin for 12 weeks . Results Nine ( 90 % ) patients achieved a sustained virological response at post‐treatment weeks 12 and 24 . One patient experienced virological failure at treatment week 6 . Sequence analyses for HCV variants in sample s from this patient identified A166S in NS3 at baseline and after breakthrough , as well as A30 K at baseline and linked S24F+M28K+A30 K variants in NS5A after breakthrough . Neither genotype 3 NS3 A166S nor NS5A A30 K variant confers any resistance to paritaprevir or ABT‐530 respectively . However , genotype 3 NS5A S24F+M28K+A30K‐linked variant confers a > 5000‐fold increase in ABT‐530 EC 50 relative to that of the wild‐type replicon . This patient 's ABT‐530 exposure was comparable to the cohort , while paritaprevir and ritonavir exposures were the lowest of all patients . No serious or severe adverse events and adverse events leading to early discontinuation were reported . Conclusions Results from this study show that ABT‐530 holds promise as part of a direct‐acting antiviral treatment regimen for HCV genotype 3 infection 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 BACKGROUND Patients chronically infected with hepatitis C virus ( HCV ) genotype 2 or 3 for whom treatment with peginterferon is not an option , or who have not had a response to prior interferon treatment , currently have no approved treatment options . In phase 2 trials , regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection . METHODS We conducted two r and omized , phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection . In one trial , patients for whom treatment with peginterferon was not an option received oral sofosbuvir and ribavirin ( 207 patients ) or matching placebo ( 71 ) for 12 weeks . In a second trial , patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks ( 103 patients ) or 16 weeks ( 98 ) . The primary end point was a sustained virologic response at 12 weeks after therapy . RESULTS Among patients for whom treatment with peginterferon was not an option , the rate of a sustained virologic response was 78 % ( 95 % confidence interval [ CI ] , 72 to 83 ) with sofosbuvir and ribavirin , as compared with 0 % with placebo ( P<0.001 ) . Among previously treated patients , the rate of response was 50 % with 12 weeks of treatment , as compared with 73 % with 16 weeks of treatment ( difference , -23 percentage points ; 95 % CI , -35 to -11 ; P<0.001 ) . In both studies , response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and , among patients with genotype 3 infection , lower among those with cirrhosis than among those without cirrhosis . The most common adverse events were headache , fatigue , nausea , and insomnia ; the overall rate of discontinuation of sofosbuvir was low ( 1 to 2 % ) . CONCLUSIONS In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option , 12 or 16 weeks of treatment with sofosbuvir and ribavirin was effective . Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis . In previously treated patients with genotype 3 infection , 16 weeks of therapy was significantly more effective than 12 weeks . ( Funded by Gilead Sciences ; POSITRON and FUSION Clinical Trials.gov numbers , NCT01542788 and NCT01604850 , respectively . ) BACKGROUND & AIMS We conducted an open-label , r and omized , phase 3 trial to determine the efficacy and safety of sofosbuvir and ribavirin , with and without peginterferon-alfa , in treatment-experienced patients with cirrhosis and hepatitis C virus ( HCV ) genotype 2 infection and treatment-naïve or treatment-experienced patients with HCV genotype 3 infection . METHODS The study was conducted at 80 sites in Europe , North America , Australia , and New Zeal and Patients were r and omly assigned ( 1:1:1 ) to groups given sofosbuvir and ribavirin for 16 weeks ( n = 196 ) ; sofosbuvir and ribavirin for 24 weeks ( n = 199 ) ; or sofosbuvir , peginterferon-alfa , and ribavirin for 12 weeks ( n = 197 ) . The primary end point was the percentage of patients with HCV RNA < 15 IU/mL 12 weeks after stopping therapy ( sustained virologic response [ SVR12 ] ) . From October 2013 until April 2014 , we enrolled and treated 592 patients - Output:	Treatment of patients with decompensated cirrhosis remains a great challenge . In summary , treatment of HCV genotype 3 patients is improving rapidly , and this population may no longer be considered a difficult-to-treat subgroup in the near future
MS21915	*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 split-mouth design is a popular design in oral health research . In the most common split-mouth study , each of two treatments are r and omly assigned to either the right or left halves of the dentition . The attractiveness of the design is that it removes a lot of inter-individual variability from the estimates of the treatment effect . However , already about 20 years ago the pitfalls of the design have been reported in the oral health literature . Yet , many clinicians are not aware of the potential problems with the split-mouth design . Further , it is our experience that most statisticians are not even aware of the existence of this design . Since most of the critical remarks appeared in the oral health literature , we argue that it is necessary to introduce the split-mouth design to a statistical audience , so that both clinicians and statisticians clearly underst and the advantages , limitations , statistical considerations , and implication s of its use in clinical trials and advise them on its use in practice A prospect i ve r and omized crossover , within-patient , controlled study was performed in 26 healthy patients to test the effect of the prophylactic local use of gauze drain impregnated with chlortetracycline ( Aureomycin 3 % , Lederle ) ointment on postoperative alveolitis formation after surgical removal of 52 bilaterally impacted m and ibular third molars . The teeth were removed on two separate occasions ; on one side drain was inserted in the socket , and on the other side no drain treatment was used for control . The influence on postoperative pain , swelling , and mouth opening ability was investigated . The results indicated a statistically significant reduction ( P = 0.02 ) in the incidence of postoperative inflammatory complications , defined as postoperative alveolitis , from 35 % in the no-drain group to 4 % in the drain group . No statistically significant difference was found between the two treatment methods with regard to pain and mouth opening reduction . There was a significant difference between the drain and no-drain treatment with regard to swelling on the 1st postoperative day in favor of the no-drain method . It is concluded that insertion of a chlortetracycline-impregnated drain may be an effective method for reducing postoperative alveolitis formation but has no beneficial effect on pain , swelling , and mouth opening reduction after impacted m and ibular third-molar surgery PURPOSE To compare the effect of total and partial wound closure techniques on immediate postoperative tissue reactions and complications after m and ibular third molar surgery . PATIENTS AND METHODS This prospect i ve , r and omized , controlled study was carried out at the Department of Oral and Maxillofacial Surgery , National Hospital , Abuja , Nigeria . Patients were r and omly allocated to partial ( group I ) and total ( group II ) wound closure groups . Data were collected on pain , trismus , swelling , and complications experienced by the patients . Data analysis was carried out with SPSS software for Windows ( version 13.0 ; SPSS , Chicago , IL ) and GenStat ( Discovery Edition , 2005 ; VSN International Ltd , Hemel Hempstead , UK ) . RESULTS We studied 82 patients , consisting of 54 female and 28 male patients , with m and ibular third molar teeth impaction . There were 40 patients ( 48.8 % ) in group I and 42 patients ( 51.2 % ) in group II . A statistically significant reduction in facial swelling ( P = .001 ) was found in group I compared with group II , but no difference was recorded for pain and trismus . Group I presented with significant postoperative reactionary bleeding ( P = .007 ) , but no difference was recorded between the 2 groups regarding dry socket and socket infection . CONCLUSION The partial wound closure technique after third molar surgery was considered to be associated with more postoperative morbidity , in view of the distressing nature of reactionary bleeding that was found to be associated with it . However , patients should be adequately informed about the possibility of attendant facial swelling each time the technique of total wound closure is used PURPOSE Postoperative variables such as pain , swelling , and trismus after surgery of the impacted lower third molars are the main concerns of dental clinicians and surgeons . Many authors cl aim that the use of a drain could help control these variables . The purpose of this study was to evaluate the effect of the use of a tube drain in impacted lower third molar surgery . MATERIAL S AND METHODS Fifty-three patients of both genders with bilateral impacted lower third molars comprised our comparative study . The patients were divided into 2 groups : in the first the suture procedure was accomplished using a drain , and in the second the suture procedure was accomplished without a drain . The postoperative pain , swelling , and trismus were evaluated at 24 hours , 72 hours , 7 days , and 15 days . RESULTS In the group in which the drain was used , the control of the swelling variable was statistically significant at 24 and 72 hours ( P < .001 ) in comparison with the group in which the drain was not used . However , pain and trismus were not statistically significant at the evaluation period . CONCLUSION The use of the drain helps to control swelling . However , it had no effect on pain or trismus The aim of this prospect i ve r and omized study was to evaluate the effect of using a rubber drain on postoperative pain , swelling and trismus after lower third molar surgery . Of 100 patients with impacted lower third molars referred for surgical extraction , there were 40 males and 60 females , aged 18 - 40 years ( mean=26+/-6.2SD ) . The patients were r and omly divided into two equal groups . In the experimental group , a Penrose rubber drain was inserted into the extraction socket near the buccal fold after surgery and left for 72 h. The control group was selected using the same criteria and treated under the same surgical protocol as the experimental group , but without use of a rubber drain . Pain , swelling and trismus were evaluated at 24h , 72 h and 5 days postoperatively in both groups . The results of the study indicate that the use of a rubber drain reduces postoperative discomfort in the form of swelling and trismus after lower third molar surgery , but seems to have no effect on pain PURPOSE The aim of this study was to estimate the frequency of postoperative complications after m and ibular third molar ( M3 ) surgery and identify the risk indicators . PATIENTS AND METHODS This was a prospect i ve cohort study of a sample of subjects having at least 1 m and ibular M3 surgically extracted at a teaching hospital in Jordan . The predictor variables were categorized as patient , anatomic , and operative specific . The outcome variables were postoperative complications recorded as present or absent . Bivariate analyses were computed , then a multivariate logistic regression model was used to identify independent predictors for the common postoperative complications . RESULTS The study sample was comprised of 149 patients who had 245 extraction s. The mean age was 21.6 + /- 3.32 years ; 64.9 % were females . In the multivariate logistic regression model , age ( P = .033 , odds ratio [ OR ] = 1.178 ) , M3 side in relation to the h and edness of the operator ( P = .048 , OR = 4.078 ) , and lingual retraction ( P = .001 , OR = 11.293 ) were the variables found as independent predictors for alveolar osteitis . The level of impaction had a significant association with trismus , and operation time acted as an independent predictor for pain ( P < .001 , OR = 1.085 ) . CONCLUSION Postoperative morbidity increases with older age , deeper impaction , M3 side differing from the h and edness of the operator , and longer procedures BACKGROUND Swelling , pain and trismus are undesirable consequences of impacted m and ibular third-molar extraction . The authors conducted a study to evaluate the effectiveness of cryotherapy , the therapeutic use of cold , in reducing undesirable consequences after surgery . METHODS Fourteen patients aged 20 to 28 years comprised the sample . The authors extracted two impacted m and ibular third molars at different times from each patient . Immediately after surgery , the patient underwent cryotherapy on one side for 30 minutes every one and one-half hours for 48 hours when he or she was awake . The patient did not receive cryotherapy on the other side . The authors performed clinical examinations to measure trismus and swelling before surgery , immediately after surgery and 24 and 48 hours after surgery . RESULTS The authors compared both sides for differences in swelling , pain and trismus in each patient . The results showed significant statistical differences in two of the five points that were used to measure the swelling ( Wilcoxon nonparametric signed rank test of linear distances between the angle of the m and ible to the pogonion and to the tragus ) . They found statistical differences between the two sides in relation to the pain ; however , they found no significant differences in relation to trismus . CONCLUSIONS Cryotherapy was effective in reducing swelling and pain in this sample . Despite playing no role in the reduction of trismus , cryotherapy was effective in reducing swelling and pain in this sample , and the authors still recommend it be used . CLINICAL IMPLICATION S Cryotherapy is helpful after third-molar extraction . Further studies need to be conducted that use larger sample s of patients and other types of therapy , such as low-level laser therapy This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence Primary and secondary closure techniques after removal of impacted third molars were compared in terms of post-operative pain and swelling . Two hundred patients with impacted third molars were r and omly divided into two groups of 100 . Panoramic radiographs were taken to assess degree of eruption and angulation of third molars . Teeth were extracted , and in Group 1 the socket was closed by hermetically suturing the flap . In Group 2 a 5 - 6 mm wedge of mucosa adjacent to the second molar was removed to obtain secondary healing . Swelling and pain were evaluated for 7 days after surgery with the VAS scale . The statistical analysis ( * analysis of variance for repeated measures , P < 0.05 ) showed that pain was greater in Group 1 , although it decreased over time similarly in the two groups ( P = 0.081 , F(6,198 ) = 3.073 * ) . Swelling was significantly worse in Group 1 ( P < 0.001 , F(6,198 ) = 44.30 * ) . In Group 1 , dehiscence of the mucosa was present in 33 % of patients at day 7 , and 2 % showed signs of re-infection with suppurative alveolitis at 30 days . Pain and swelling were less severe with secondary healing than with primary healing The insertion of a small surgical tube drain with primary wound closure ( drain group ) was compared to a simple primary wound closure ( no drain group ) after removal of impacted third molars . Surgery was performed on 23 patients in a r and omized cross-over fashion . The operation time was found to be significantly longer and mouth opening significantly wider in the immediate postoperative period in the drain group subjects as compared to the no drain group ( P > or = 0.01 ) . There was no significant difference in the severity of pain between the two groups . Facial swelling was found to be significantly less in the drain group subjects ( P > or = 0.01 ) . The number of patients with wound breakdown , edema , and bleeding was found to be less in the drain group than in the no drain group . Thus , the postoperative problems , in general , were less in the small surgical drain group as compared to the no drain group Extraction of impacted m and ibular third molars is one of the most common procedures in the oral cavity and often is followed by pain , swelling , and post extraction alveolitis and trismus . It has been suggested that postoperative discomfort is in relation to the type of surgical wound healing . The aim of this study was to compare pain , swelling , and maximum mouth opening in two groups of patients with primary and secondary wound healing after impacted m and ibular third molar surgery . Thirty-two patients were enrolled in this study and r and omly divided into two equal groups , quantitatively and by gender . After the surgical procedures , 16 patients received primary wound closure , while the other 16 participants received secondary wound closure . A visual analog scale was used to collect pain data three days after the surgeries . A checklist was used to record data regarding swelling size and maximum mouth opening before , immediately following , three days after , and one week after surgery . Frequency tests and a t-test were used for statistical analysis and a P value of < 0.05 was considered to be statistically significant . Patients in the secondary wound healing group showed statistically significant lower discomfort regarding pain , swelling size , and maximal mouth opening compared to the primary wound healing group . The authors suggest the use of secondary wound healing closure to reduce postoperative complications such as pain , maximal mouth opening , and swelling size after impacted m and ibular third molar extraction PURPOSE Pain , swelling , and trismus are the most common complications associated with third molar surgery . Several Output:	The results do not support a preference for either approach
MS21916	*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 Whiplash‐associated disorders are common and incur considerable expense in social and economic terms . There are no known effective treatments for those people whose pain and disability persist beyond 3 months . We conducted a r and omized , assessor‐blinded , controlled trial at two centres in Australia . All participants received 3 advice sessions . In addition the experimental group participated in 12 exercise sessions over 6 weeks . Primary outcomes were pain intensity , pain bothersomeness and function measured at 6 weeks and 12 months . Exercise and advice was more effective than advice alone at 6 weeks for all primary outcomes but not at 12 months . The effect of exercise on the 0–10 pain intensity scale was −1.1 ( 95%CI −1.8 to −0.3 , p = 0.005 ) at 6 weeks and −0.2 ( 0.6 to −1.0 , p = 0.59 ) at 12 months ; on the bothersomeness scale the effect was −1.0 ( −1.9 to −0.2 , p = 0.003 ) at 6 weeks and 0.3 ( −0.6 to 1.3 , p = 0.48 ) at 12 months . The effect on function was 0.9 ( 0.3 to 1.6 , p = 0.006 ) at 6 weeks and 0.6 ( −0.1 to 1.4 , p = 0.10 ) at 12 months . High levels of baseline pain intensity were associated with greater treatment effects at 6 weeks and high levels of baseline disability were associated with greater treatment effects at 12 months . In the short‐term exercise and advice is slightly more effective than advice alone for people with persisting pain and disability following whiplash . Exercise is more effective for subjects with higher baseline pain and disability Background The evidence that exercise intervention is effective for treatment of chronic low back pain comes from trials that are not placebo-controlled . Objective The purpose of this study was to investigate the efficacy of motor control exercise for people with chronic low back pain . Design This was a r and omized , placebo-controlled trial . Setting The study was conducted in an outpatient physical therapy department in Australia . Patients The participants were 154 patients with chronic low back pain of more than 12 weeks ’ duration . Intervention Twelve sessions of motor control exercise ( ie , exercises design ed to improve function of specific muscles of the low back region and the control of posture and movement ) or placebo ( ie , detuned ultrasound therapy and detuned short-wave therapy ) were conducted over 8 weeks . Measurements Primary outcomes were pain intensity , activity ( measured by the Patient-Specific Functional Scale ) , and patient 's global impression of recovery measured at 2 months . Secondary outcomes were pain ; activity ( measured by the Patient-Specific Functional Scale ) ; patient 's global impression of recovery measured at 6 and 12 months ; activity limitation ( measured by the Rol and -Morris Disability Question naire ) at 2 , 6 , and 12 months ; and risk of persistent or recurrent pain at 12 months . Results The exercise intervention improved activity and patient 's global impression of recovery but did not clearly reduce pain at 2 months . The mean effect of exercise on activity ( measured by the Patient-Specific Functional Scale ) was 1.1 points ( 95 % confidence interval [CI]=0.3 to 1.8 ) , the mean effect on global impression of recovery was 1.5 points ( 95 % CI=0.4 to 2.5 ) , and the mean effect on pain was 0.9 points ( 95 % CI=−0.01 to 1.8 ) , all measured on 11-point scales . Secondary outcomes also favored motor control exercise . Limitation Clinicians could not be blinded to the intervention they provided . Conclusions Motor control exercise produced short-term improvements in global impression of recovery and activity , but not pain , for people with chronic low back pain . Most of the effects observed in the short term were maintained at the 6- and 12-month follow-ups In r and omized controlled trials , no single definition of response is ideal for all purpose s. We propose a method to present in a simple fashion the likelihood of response over a full range of response levels , which will facilitate a better underst and ing of clinical trial data . We present the technique called the cumulative proportion of responders analysis ( CPRA ) and its application to four pain clinical trial data sets as examples . The CPRA can be used to present the proportion of responders over the entire range of possible cut-off points as a graph . This allows the reader to compare treatment groups at any responder level that is valid for their patient population . Whether as a primary or secondary approach to a clinical trial of pain therapy , the display of data in a CPRA format may be useful in the underst and ing of results and applicability to patient care Background Reporting numbers needed to treat ( NNT ) improves interpretability of trial results . It is unusual that continuous outcomes are converted to numbers of individual responders to treatment ( i.e. , those who reach a particular threshold of change ) ; and deteriorations prevented are only rarely considered . We consider how numbers needed to treat can be derived from continuous outcomes ; illustrated with a worked example showing the methods and challenges . Methods We used data from the UK BEAM trial ( n = 1 , 334 ) of physical treatments for back pain ; originally reported as showing , at best , small to moderate benefits . Participants were r and omised to receive ' best care ' in general practice , the comparator treatment , or one of three manual and /or exercise treatments : ' best care ' plus manipulation , exercise , or manipulation followed by exercise . We used established consensus thresholds for improvement in Rol and -Morris disability question naire scores at three and twelve months to derive NNTs for improvements and for benefits ( improvements gained+deteriorations prevented ) . Results At three months , NNT estimates ranged from 5.1 ( 95 % CI 3.4 to 10.7 ) to 9.0 ( 5.0 to 45.5 ) for exercise , 5.0 ( 3.4 to 9.8 ) to 5.4 ( 3.8 to 9.9 ) for manipulation , and 3.3 ( 2.5 to 4.9 ) to 4.8 ( 3.5 to 7.8 ) for manipulation followed by exercise . Corresponding between-group mean differences in the Rol and -Morris disability question naire were 1.6 ( 0.8 to 2.3 ) , 1.4 ( 0.6 to 2.1 ) , and 1.9 ( 1.2 to 2.6 ) points . Conclusion In contrast to small mean differences originally reported , NNTs were small and could be attractive to clinicians , patients , and purchasers . NNTs can aid the interpretation of results of trials using continuous outcomes . Where possible , these should be reported alongside mean differences . Challenges remain in calculating NNTs for some continuous outcomes .Trial Registration UK BEAM trial registration : IS RCT N32683578 BACKGROUND Evidence suggests that brief physiotherapy programmes are as effective for acute whiplash-associated disorders as more comprehensive programmes ; however , whether this also holds true for chronic whiplash-associated disorders is unknown . We aim ed to estimate the effectiveness of a comprehensive exercise programme delivered by physiotherapists compared with advice in people with a chronic whiplash-associated disorder . METHODS PROMISE is a two group , pragmatic r and omised controlled trial in patients with chronic ( > 3 months and < 5 years ) grade 1 or 2 whiplash-associated disorder . Participants were r and omly assigned by a computer-generated r and omisation schedule to receive either the comprehensive exercise programme ( 20 sessions ) or advice ( one session and telephone support ) . Sealed opaque envelopes were used to conceal allocation . The primary outcome was pain intensity measured on a 0 - 10 scale . Outcomes were measured at baseline , 14 weeks , 6 months , and 12 months by a masked assessor . Analysis was by intention to treat , and treatment effects were calculated with linear mixed models . The trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12609000825257 . FINDINGS 172 participants were allocated to either the comprehensive exercise programme ( n=86 ) or advice group ( n=86 ) ; 157 ( 91 % ) were followed up at 14 weeks , 145 ( 84 % ) at 6 months , and 150 ( 87 % ) at 12 months . A comprehensive exercise programme was not more effective than advice alone for pain reduction in the participants . At 14 weeks the treatment effect on a 0 - 10 pain scale was 0·0 ( 95 % CI -0·7 to 0·7 ) , at 6 months 0·2 ( -0·5 to 1·0 ) , and at 12 months -0·1 ( -0·8 to 0·6 ) . CNS hyperexcitability and symptoms of post-traumatic stress did not modify the effect of treatment . We recorded no serious adverse events . INTERPRETATION We have shown that simple advice is equally as effective as a more intense and comprehensive physiotherapy exercise programme . The need to identify effective and affordable strategies to prevent and treat acute through to chronic whiplash associated disorders is an important health priority . Future avenues of research might include improving underst and ing of the mechanisms responsible for persistent pain and disability , investigating the effectiveness and timing of drugs , and study of content and delivery of education and advice . FUNDING The National Health and Medical Research Council of Australia , Motor Accidents Authority of New South Wales , and Motor Accident Insurance Commission of Queensl and A post-hoc individual patient matching procedure was recently proposed within the context of parallel group r and omized clinical trials ( RCTs ) as a method for estimating treatment effect . In this paper , we consider a post-hoc individual patient matching problem within a parallel group RCT as a multi- objective decision-making problem focussing on the trade-off between the quality of individual matches and the overall percentage of matching . Using acute stroke trials as a context , we utilize exact optimization and simulation techniques to investigate a complex relationship between the overall percentage of individual post-hoc matching , the size of the respective RCT , and the quality of matching on variables highly prognostic for a good functional outcome after stroke , as well as the dispersion in these variables . It is empirically confirmed that a high percentage of individual post-hoc matching can only be achieved when the differences in prognostic baseline variables between individually matched subjects within the same pair are sufficiently large and that the unmatched subjects are qualitatively different to the matched ones . It is concluded that the post-hoc individual matching as a technique for treatment effect estimation in parallel-group RCTs should be exercised with caution because of its propensity to introduce significant bias and reduce validity . If used with appropriate caution and thorough evaluation , this approach can complement other viable alternative approaches for estimating the treatment effect Abstract Practice guidelines recommend various types of exercise and manipulative therapy for chronic back pain but there have been few head‐to‐head comparisons of these interventions . We conducted a r and omized controlled trial to compare effects of general exercise , motor control exercise and manipulative therapy on function and perceived effect of intervention in patients with chronic back pain . Two hundred and forty adults with non‐specific low back pain ⩾3 months were allocated to groups that received 8 weeks of general exercise , motor control exercise or spinal manipulative therapy . General exercise included strengthening , stretching and aerobic exercises . Motor control exercise involved retraining specific trunk muscles using ultrasound feedback . Spinal manipulative therapy included joint mobilization and manipulation . Primary outcomes were patient‐specific function ( PSFS , 3–30 ) and global perceived effect ( GPE , −5 to 5 ) at 8 weeks . These outcomes were also measured at 6 and 12 months . Follow‐up was 93 % at 8 weeks and 88 % at 6 and 12 months . The motor control exercise group had slightly better outcomes than the general exercise group at 8 weeks ( between‐group difference : PSFS 2.9 , 95 % CI : 0.9–4.8 ; GPE 1.7 , 95 % CI : 0.9–2.4 ) , as did the spinal manipulative therapy group ( PSFS 2.3 , 95 % CI : 0.4–4.2 ; GPE 1.2 , 95 % CI : 0.4–2.0 ) . The groups had similar outcomes at 6 and 12 months . Motor control exercise and spinal manipulative therapy produce slightly better short‐term function and perceptions of effect than general exercise , but not better medium or long‐term effects , in patients with chronic non‐specific back pain Background Low back pain is a highly prevalent and disabling condition worldwide . Clinical guidelines for the management of patients with acute low back pain recommend first-line treatment consisting of advice , reassurance and simple analgesics . Exercise is also commonly prescribed to these patients . The primary aim of this study was to evaluate the short-term effect of adding the McKenzie method to the first-line care of patients with acute low back pain . Methods A multi-centre r and omized controlled trial with a 3-month follow-up was conducted between September 2005 and June 2008 . Patients seeking care for acute non-specific low back pain from primary care medical practice s were screened . Eligible participants were assigned to receive a treatment programme based on the McKenzie method and first-line care ( advice , reassurance and time-contingent acetaminophen ) or first-line care alone , for 3 weeks . Primary outcome measures included pain ( 0 - 10 Numeric Rating Scale ) over the first seven days , pain at 1 week , pain at 3 weeks and global perceived effect ( -5 to 5 scale ) at 3 weeks . Treatment effects were estimated using linear mixed models . Results One hundred and forty-eight participants were r and omized into study groups , of whom 138 ( 93 % ) completed the last follow-up . The addition of the McKenzie method to first-line care produced statistically significant but small reductions in pain when compared to first-line care alone : mean of -0.4 points ( 95 % confidence interval , -0.8 to -0.1 ) at 1 week , -0.7 points ( 95 % Output:	We found no compelling evidence suggesting that outcomes were bimodally distributed for any of the intervention groups . Responder analysis would not meaningfully alter our interpretation of these data compared with the mean between group difference . Our findings suggest that bimodal distribution of outcomes should not be assumed in interventions for spinal pain and do not support the automatic prioritization of responder analysis over the between group difference in the evaluation of treatment effectiveness for pain . PERSPECTIVE Secondary analysis of clinical trials of nonsurgical interventions for spinal pain found no evidence for bimodally distributed outcomes . The findings do not support the automatic prioritization of responder analyses over the average between group difference in the evaluation of treatment effectiveness for spinal pain
MS21917	*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 aim of this study was to evaluate the safety and effectiveness of erlotinib plus DC/CIK in maintenance therapy of advanced non – small cell lung cancer . After 4 cycles of the 2-drug regimen treatment with platinum , the 54 patients with non – small cell lung cancer in phase IIIb or IV reached stable or beyond stable stages . The patients were then r and omly divided into 2 groups . One group was treated with erlotinib therapy ( erlotinib group ) , and the other was treated with DC/CIK plus erlotinib ( DC/CIK plus erlotinib group ) . The progression-free survival of the erlotinib group and the DC/CIK plus erlotinib group was 3.98 months ( 95 % CI , 3.56–4.40 ) and 5.02 months ( 95 % CI , 4.32–5.72 ) ( P=0.002 ) , respectively . The median overall survival of the erlotinib group and the DC/CIK plus erlotinib group was 9.9 months ( 95 % CI , 9.1–10.6 ) and 10.5 months ( 95 % CI , 9.6–11.4 ) ( P=0.29 ) , respectively . The levels of CD3 + , CD4 + , and CD8 + were significantly different before and after the treatment in the DC/CIK plus erlotinib group , but not in the erlotinib group . There was no significant difference in toxicity between the 2 groups . In conclusion , there was no statistically significant difference in overall survival between DC/CIK plus erlotinib and erlotinib as maintenance therapy . DC/CIK plus erlotinib was well tolerated with a manageable safety profile BACKGROUND The phase III , r and omized , open-label ENSURE study ( NCT01342965 ) evaluated first-line erlotinib versus gemcitabine/cisplatin ( GP ) in patients from China , Malaysia and the Philippines with epidermal growth factor receptor ( EGFR ) mutation-positive non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0 - 2 were r and omized 1:1 to receive erlotinib ( oral ; 150 mg once daily until progression/unacceptable toxicity ) or GP [ G 1250 mg/m(2 ) i.v . days 1 and 8 ( 3-weekly cycle ) ; P 75 mg/m(2 ) i.v . day 1 , ( 3-weekly cycle ) for up to four cycles ] . Primary end point : investigator-assessed progression-free survival ( PFS ) . Other end points include objective response rate ( ORR ) , overall survival ( OS ) , and safety . RESULTS A total of 217 patients were r and omized : 110 to erlotinib and 107 to GP . Investigator-assessed median PFS was 11.0 months versus 5.5 months , erlotinib versus GP , respectively [ hazard ratio ( HR ) , 0.34 , 95 % confidence interval ( CI ) 0.22 - 0.51 ; log-rank P < 0.0001 ] . Independent Review Committee-assessed median PFS was consistent ( HR , 0.42 ) . Median OS was 26.3 versus 25.5 months , erlotinib versus GP , respectively ( HR , 0.91 , 95 % CI 0.63 - 1.31 ; log-rank P = .607 ) . ORR was 62.7 % for erlotinib and 33.6 % for GP . Treatment-related serious adverse events ( AEs ) occurred in 2.7 % versus 10.6 % of erlotinib and GP patients , respectively . The most common grade ≥3 AEs were rash ( 6.4 % ) with erlotinib , and neutropenia ( 25.0 % ) , leukopenia ( 14.4 % ) , and anemia ( 12.5 % ) with GP . CONCLUSION These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC ( NCT01342965 ) BACKGROUND The OPTIMAL study found that erlotinib improved progression-free survival ( PFS ) versus st and ard chemotherapy in Chinese patients with advanced EGFR mutation-positive non-small-cell lung cancer ( NSCLC ) . This report describes the quality of life ( QoL ) and up date d PFS analyses from this study . PATIENTS AND METHODS Chinese patients ≥ 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR ( exon 19 deletion or exon 21 L858R point mutation ) received erlotinib ( 150 mg/day ; n = 82 ) or gemcitabine-carboplatin ( n = 72 ) . The primary efficacy end point was PFS ; QoL was assessed using the Functional Assessment of Cancer Therapy-Lung ( FACT-L ) question naire , Trial Outcome Index ( TOI ) and Lung Cancer Subscale ( LCS ) . RESULTS Patients receiving erlotinib experienced clinical ly relevant improvements in QoL compared with the chemotherapy group in total FACT-L , TOI and LCS ( P < 0.0001 for all scales ) . Erlotinib scored better than chemotherapy for all FACT-L subscales from baseline to cycles 2 and 4 ( non-significant ) . In the up date d analysis , PFS was significantly longer for erlotinib than chemotherapy ( median PFS 13.7 versus 4.6 months ; HR = 0.164 , 95 % CI = 0.105 - 0.256 ; P < 0.0001 ) , which was similar to the previously reported primary analysis . CONCLUSION Erlotinib improves QoL compared with st and ard chemotherapy in the first-line treatment of patients with EGFR mutation-positive advanced NSCLC AIM This analysis investigates incidence and time course of rash in the EURTAC study . MATERIAL S & METHODS Patients with EGFR mutation-positive non-small-cell lung cancer were r and omized 1:1 to receive once daily erlotinib or 3-weekly cycles of chemotherapy . RESULTS Of the 86 erlotinib-treated patients , 71 reported rash . Median time to first rash appearance was 0.7 months . Most patients ( n = 65 ) had the same or lower grade rash at final assessment compared with initial assessment . Of the 21 patients with decreased rash grade between initial and final assessment s , 61.9 % received no erlotinib dose modification , 42.8 % had no concomitant rash treatment . CONCLUSION Most rash cases were mild , occurred within 1 month of erlotinib treatment , and rapidly improved without the need for erlotinib dose alterations BACKGROUND The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer ( NSCLC ) . We aim ed to compare the efficacy and safety of afatinib and gefitinib in this setting . METHODS This multicentre , international , open-label , exploratory , r and omised controlled phase 2B trial ( LUX-Lung 7 ) was done at 64 centres in 13 countries . Treatment-naive patients with stage IIIB or IV NSCLC and a common EGFR mutation ( exon 19 deletion or Leu858Arg ) were r and omly assigned ( 1:1 ) to receive afatinib ( 40 mg per day ) or gefitinib ( 250 mg per day ) until disease progression , or beyond if deemed beneficial by the investigator . R and omisation , stratified by EGFR mutation type and status of brain metastases , was done central ly using a vali date d number generating system implemented via an interactive voice or web-based response system with a block size of four . Clinicians and patients were not masked to treatment allocation ; independent review of tumour response was done in a blinded manner . Co primary endpoints were progression-free survival by independent central review , time-to-treatment failure , and overall survival . Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug . This ongoing study is registered with Clinical Trials.gov , number NCT01466660 . FINDINGS Between Dec 13 , 2011 , and Aug 8 , 2013 , 319 patients were r and omly assigned ( 160 to afatinib and 159 to gefitinib ) . Median follow-up was 27·3 months ( IQR 15·3 - 33·9 ) . Progression-free survival ( median 11·0 months [ 95 % CI 10·6 - 12·9 ] with afatinib vs 10·9 months [ 9·1 - 11·5 ] with gefitinib ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·57 - 0·95 ] , p=0·017 ) and time-to-treatment failure ( median 13·7 months [ 95 % CI 11·9 - 15·0 ] with afatinib vs 11·5 months [ 10·1 - 13·1 ] with gefitinib ; HR 0·73 [ 95 % CI 0·58 - 0·92 ] , p=0·0073 ) were significantly longer with afatinib than with gefitinib . Overall survival data are not mature . The most common treatment-related grade 3 or 4 adverse events were diarrhoea ( 20 [ 13 % ] of 160 patients given afatinib vs two [ 1 % ] of 159 given gefitinib ) and rash or acne ( 15 [ 9 % ] patients given afatinib vs five [ 3 % ] of those given gefitinib ) and liver enzyme elevations ( no patients given afatinib vs 14 [ 9 % ] of those given gefitinib ) . Serious treatment-related adverse events occurred in 17 ( 11 % ) patients in the afatinib group and seven ( 4 % ) in the gefitinib group . Ten ( 6 % ) patients in each group discontinued treatment due to drug-related adverse events . 15 ( 9 % ) fatal adverse events occurred in the afatinib group and ten ( 6 % ) in the gefitinib group . All but one of these deaths were considered unrelated to treatment ; one patient in the gefitinib group died from drug-related hepatic and renal failure . INTERPRETATION Afatinib significantly improved outcomes in treatment-naive patients with EGFR-mutated NSCLC compared with gefitinib , with a manageable tolerability profile . These data are potentially important for clinical decision making in this patient population . FUNDING Boehringer Ingelheim BACKGROUND Bevacizumab and erlotinib target different tumour growth pathways with little overlap in their toxic-effect profiles . On the basis of promising results from a phase 1/2 trial assessing safety and activity of erlotinib plus bevacizumab for recurrent or refractory non-small-cell lung cancer ( NSCLC ) , we aim ed to assess efficacy and safety of this combination in a phase 3 trial . METHODS In our double-blind , placebo-controlled , r and omised phase 3 trial ( BeTa ) , we enrolled patients with recurrent or refractory NSCLC who presented to 177 study sites in 12 countries after failure of first-line treatment . Patients were r and omly allocated in a one-to-one ratio to receive erlotinib plus bevacizumab ( bevacizumab group ) or erlotinib plus placebo ( control group ) according to a computer-generated r and omisation sequence by use of an interactive voice response system . The primary endpoint was overall survival in all enrolled patients . Patients , study staff , and investigators were masked to treatment assignment . We assessed safety by calculation of incidence of adverse events and tissue was collected for biomarker analyses . This trial is registered with Clinical Trials.gov , number NCT00130728 . FINDINGS Overall survival did not differ between 317 controls and 319 patients in the bevacizumab group ( hazard ratio [ HR ] 0·97 , 95 % CI 0·80 - 1·18 , p=0·7583 ) . Median overall survival was 9·3 months ( IQR 4·1 - 21·6 ) for patients in the bevacizumab group compared with 9·2 months ( 3·8 - 20·2 ) for controls . Progression-free survival seemed to be longer in the bevacizumab group ( 3·4 months [ 1·4 - 8·4 ] ) than in the control group ( 1·7 months [ 1·3 - 4·1 ] ; HR 0·62 , 95 % CI 0·52 - 0·75 ) and objective response rate suggested some clinical activity of bevacizumab and erlotinib . However , these secondary endpoint differences could not be defined as significant because the study prespecified that the primary endpoint had to be significant before testing of secondary endpoints could be done , to control type I error rate . In the bevacizumab group , 130 ( 42 % ) of Output:	Although data for erlotinib plus bevacizumab came from a single Phase 2 study , the results of the NMA suggest that adding bevacizumab to erlotinib may be a promising approach to improving the outcomes achieved with EGFR-TKI monotherapy in patients with advanced EGFR+ NSCLC
MS21918	*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 Vietnamese have higher liver cancer rates than any other racial/ethnic group in the United States . Approximately 80 % of liver cancers are etiologically associated with hepatitis B virus ( HBV ) infection , which is endemic in Southeast Asia . METHODS A telephone survey of r and omly selected Vietnamese households ( n = 75 ) was conducted during 1998 to examine HBV knowledge among Seattle 's Vietnamese community . The question naire included items related to the transmission of HBV , the possible sequelae of infection , and disease prevention . RESULTS The response rate was 70 % among reachable and eligible households . Prior to being provided with a description of the disease , two thirds of our respondents had heard of HBV infection . Less than 60 % knew that asymptomatic individuals can transmit the disease to others . Most thought that HBV infection can cause liver cancer ( 63 % ) and death ( 80 % ) . However , only a minority knew that infection can be lifelong ( 38 % ) and incurable ( 22 % ) . Finally , 28 % had never heard of the HBV vaccine . There were significant associations between knowledge and educational level as well as home ownership . CONCLUSIONS The findings suggest that Vietnamese immigrants have low levels of knowledge about HBV infection , and indicate a need for targeted educational interventions aim ed at reducing HBV-related liver cancer mortality BACKGROUND & AIMS Little is known about the HCV prevalence in non-Western migrant population s. To determine whether targeted HCV screening and prevention programs for migrants are needed , we examined HCV prevalence and determinants among non-Western , Western migrants , and the native Dutch population in the Netherl and s. METHODS Data were obtained from four surveys : ( 1 ) 3895 heterosexual visitors recruited during biannual surveys at the STI-clinic Amsterdam , 2007 - 2009 ; ( 2 ) r and om sample of 4563 pregnant women in Amsterdam , 2003 ; ( 3 ) population -based r and om sample of 1309 inhabitants of Amsterdam , 2004 ; ( 4 ) population -based r and om sample of 4428 people living in the Netherl and s , 2006 - 2007 . Characteristics associated with HCV-positivity were examined and phylogenetic analysis was used to obtain insight in the geographical origin of HCV strains . RESULTS HCV seroprevalence in the four surveys was low ( 0.3 - 0.6 % ) . In total 4860/14,195 ( 34 % ) were non-Western and 9329/14,195 ( 66 % ) Western participants ( including Dutch ) . First-generation non-Western migrants were more likely to be HCV-positive ( 0.7 - 2.3 % ) than Western participants ( 0.1 - 0.4 % ) . Except for survey 3 , second-generation non-Western migrants had a lower HCV prevalence than first-generation migrants , comparable to Western migrants and the Dutch population . Phylogenetic analysis showed that the majority of the HCV-positive , first-generation non-Western non-European migrants were infected with endemic strains which are rarely observed in Europe . CONCLUSIONS First-generation non-Western migrants are at increased risk for HCV . Phylogenetic analysis suggests that transmission likely took place in the country of origin , causing introduction but no further transmission of endemic HCV strains in the Netherl and s. HCV screening and prevention programs should target first-generation , but not second-generation , non-Western migrants This study examines mortality patterns among Canadian immigrants , including both refugees and non-refugees , 1980–1998 . Records of a stratified r and om sample of Canadian immigrants l and ing between 1980–1990 ( N = 369,936 ) were probabilistically linked to mortality data ( 1980–1998 ) . Mortality rates among immigrants were compared to those of the general Canadian population , stratifying by age , sex , immigration category , region of birth and time in Canada . Multivariate analysis examined mortality risks for various immigrant subgroups . Although immigrants presented lower all-cause mortality than the general Canadian population ( SMR between 0.34 and 0.58 ) , some cause-specific mortality rates were elevated among immigrants , including mortality from stroke , diabetes , infectious diseases ( AIDS and hepatitis among certain subgroups ) , and certain cancers ( liver and nasopharynx ) . Mortality rates differed by region of birth , and were higher among refugees than other immigrants . These results support the need to consider the heterogeneity of immigrant population s and vulnerable subgroups when developing targeted interventions BACKGROUND Liver cancer , a significant health problem in Chinese , can be controlled through HBV blood testing , vaccination , and community education about HBV . The PRECEDE framework has been very helpful in identifying factors associated with health practice s. OBJECTIVES The objective was to identify factors associated with HBV testing in Chinese Canadians , using the PRECEDE framework . METHODS Five hundred and thirty-three r and omly selected Chinese Canadian adults were interviewed about HBV blood testing practice s. Factors were grouped as predisposing , reinforcing and enabling . RESULTS Fifty-five percent had received HBV blood testing . Several predisposing factors , all reinforcing factors and one enabling factor were associated with HBV testing in bivariate analysis . A physician 's recommendation for testing was the strongest factor associated with testing in multiple logistic regression analysis ( OR=4.4 , p<0.0001 ) . INTERPRETATION Many Chinese Canadian adults in Vancouver have not been tested for HBV . Continuing educational efforts are needed and the PRECEDE framework can inform the development of health education interventions Southeast Asians have higher liver cancer rates than any other racial/ethnic group in the US . Approximately 80 percent of liver cancers are etiologically associated with hepatitis B virus ( HBV ) infection which is endemic in Southeast Asia . An in-person survey of Cambodian women ( n = 320 ) was conducted in Seattle , Washington , during 1999 . The question naire included items about HBV knowledge , beliefs , and practice s. Prior to being provided with a description of the disease , only about one-half ( 56 percent ) of our respondents had heard of HBV infection . Less than one-quarter ( 23 percent ) of the study group thought that asymptomatic individuals can transmit the disease to others . Most thought that HBV infection can cause liver cancer ( 54 percent ) and death ( 72 percent ) . However , a minority thought that infection can be lifelong ( 24 percent ) and incurable ( 15 percent ) . Only 38 percent reported they had been serologically tested for HBV . Finally , of those who had been tested and thought they were susceptible , two-thirds ( 67 percent ) had not been vaccinated . Lower levels of education were associated with lower levels of HBV knowledge and serologic testing . Our findings suggest that Cambodian immigrants have low levels of HBV knowledge , serologic testing , and vaccination ; and demonstrate a need for targeted educational interventions aim ed at reducing HBV-related liver cancer mortality among Southeast Asian communities Output:	Many immigrants lacked adequate knowledge of aetiology , symptoms , transmission risk factors , prevention strategies , and treatment , of hepatitis HBV and HCV . Ethnicity , gender , better education , higher income , and English proficiency influenced variations in levels and forms of knowledge . Conclusion Immigrants are vulnerable to HBV and HCV , and risk life-threatening complications from these infections because of poor knowledge and help-seeking behaviour .
MS21919	*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 OBJECTIVES To evaluate whether the capillary refill test can correctly differentiate between hypovolemic and euvolemic emergency department patients . DESIGN A prospect i ve , nonr and omized , nonblinded time series . SETTING The orthostatic and hypotensive patients were seen in a university hospital ED with 44,000 visits per year . Blood donors were studied in the hospital 's blood donor center . TYPE OF PARTICIPANTS Thirty-two adult ED patients who presented with a history suggestive of hypovolemia and either abnormal orthostatic vital signs ( 19 ) or frank hypotension ( 13 ) , and 47 volunteer blood donors who ranged in age from 19 to 83 participated . INTERVENTIONS Capillary refill was measured before rehydration in the ED subjects and , in the donor group , before and after a 450-mL blood donation . MEASUREMENTS Sensitivity , specificity , accuracy , and positive and negative predictive values were calculated . Analyses were stratified by age , sex , and study group . MAIN RESULTS For the blood donor group , mean capillary refill time before donation was 1.4 seconds and after donation was 1.1 seconds . Mean capillary refill time for the orthostatic group was 1.9 seconds and for the hypotensive group was 2.8 seconds . When scored with age-sex specific upper limits of normal , the sensitivity of capillary refill in identifying hypovolemic patients was 6 % for the 450-mL blood loss group , 26 % for the orthostatic group , and 46 % for the hypotensive group . The accuracy of capillary refill in a patient with a 50 % prior probability of hypovolemia is 64 % . Orthostatic vital signs were found to be more sensitive and specific than capillary refill in detecting the 450-mL blood loss . CONCLUSION Capillary refill does not appear to be a useful test for detecting mild-to-moderate hypovolemia in adults Background : The research -to- practice gap is at the heart of the problem in the underuse of nondrug complementary methods to manage postoperative pain . Purpose : To show how the six steps of the Collaborative Research Utilization ( CRU ) model can be used to translate research into practice , using an example of nondrug pain management protocol s. Methods : The CRU model was used to translate empirically tested nondrug interventions for surgical pain management enhancement into cost-effective , easy-to-use , best- practice nursing interventions , using tailored patient teaching . Results : The preliminary findings of the sub study in the context of the CRU model are reported . Discussion : The CRU model was successful in changing patients ' knowledge , attitudes , and use of nondrug interventions for pain management . Further research is needed in heterogeneous population s. Organization receptivity to research and a well-integrated computerized documentation system for cueing clinicians ' pain management practice s are key for effectiveness of change It is not uncommon for a decade to pass between the time a research problem is identified and the time that research -based solutions are translated into st and ards for care . This quasi-experimental study demonstrated the effectiveness of a collaborative research utilization model directed towards the transfer of specific research -based knowledge ( pain assessment ) into practice for the purpose of helping to solve pain management problems . At the same time , nurses who participated in the model significantly improved their competency in research utilization and their attitudes towards research when compared to a control group who did not participate in the model Objective Peripheral perfusion in critically ill patients frequently is assessed by use of clinical signs . Recently , the pulse oximetry signal has been suggested to reflect changes in peripheral perfusion . A peripheral perfusion index based on analysis of the pulse oximetry signal has been implemented in monitoring systems as an index of peripheral perfusion . No data on the variation of this index in the normal population are available , and clinical application of this variable in critically ill patients has not been reported . We therefore studied the variation of the peripheral perfusion index in healthy adults and related it to the central -to-toe temperature difference and capillary refill time in critically ill patients after changes in clinical signs of peripheral perfusion . Design Prospect i ve study . Setting University-affiliated teaching hospital . Patients One hundred eight healthy adult volunteers and 37 adult critically ill patients . Interventions None . Measurements and Main Results Capillary refill time , peripheral perfusion index , and arterial oxygen saturation were measured in healthy adults ( group 1 ) . Capillary refill time , peripheral perfusion index , arterial oxygen saturation , central -to-toe temperature difference , and hemodynamic variables were measured in critically ill patients ( group 2 ) during different peripheral perfusion profiles . Poor peripheral perfusion was defined as a capillary refill time > 2 secs and central -to-toe temperature difference ≥7 ° C . Peripheral perfusion index and arterial oxygen saturation were measured by using the Philips Medical Systems Viridia/56S monitor . In group 1 , measurements were made before and after a meal . In group 2 , two measurements were made , with the second measurement taken when the peripheral perfusion profile had changed . A total of 216 measurements were carried out in group 1 . The distribution of the peripheral perfusion index was skewed and values ranged from 0.3 to 10.0 , median 1.4 ( inner quartile range , 0.7–3.0 ) . Seventy-four measurements were carried out in group 2 . A significant correlation between the peripheral perfusion index and the core-to-toe temperature difference was found ( R2= .52;p < .001 ) . A cutoff peripheral perfusion index value of 1.4 ( calculated by constructing a receiver operating characteristic curve ) best reflected the presence of poor peripheral perfusion in critically ill patients . Changes in peripheral perfusion index and changes in core-to-toe temperature difference correlated significantly ( R = .52 , p < .001 ) . Conclusions The peripheral perfusion index distribution in the normal population is highly skewed . Changes in the peripheral perfusion index reflect changes in the core-to-toe temperature difference . Therefore , peripheral perfusion index measurements can be used to monitor peripheral perfusion in critically ill patients The influence of gender , local temperature , and systemic blood pressure on human capillary pressure is unknown . Finger nail fold capillary pressure was therefore directly measured in 74 healthy supine volunteers ( 40 female ) at midaxillary level . Capillary pressure was lower in women than in men ( 15.9 + /- 3.0 vs. 18.2 + /- 2.3 mmHg ; P = 0.001 ) , particularly in premenopausal women , but was not related to systolic , diastolic , or mean blood pressure . Capillary pulse pressure amplitude was related to skin temperature , an effect more marked in women ( P = 0.003 ) . There was a significant association between skin temperature and the time taken for the systolic pressure rise to reach the capillary , in women only ( r = -0.69 , P < 0.001 ) . Increasing age reduced the high-frequency waves in the pressure waveform [ 2nd harmonic percentage of fundamental : r = -0.52 and P = 0.002 ( women ) , r = -0.52 and P = 0.004 ( men ) ] . Thus mean capillary pressure and the pressure waveform may be influenced by gender , age , and skin temperature , illustrating the necessity to adequately match control groups during assessment s of capillary pressure pathophysiology Output:	AND RECOMMENDATIONS Isolated performance of capillary refill assessment is of limited value and no nursing interventions rely solely on this measure . Future research should be directed toward evaluation and comparative analyses of alternate methods of evaluating peripheral perfusion
MS21920	*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 Antidepressant medication is frequently prescribed for patients with anorexia nervosa . OBJECTIVE To determine whether fluoxetine can promote recovery and prolong time-to-relapse among patients with anorexia nervosa following weight restoration . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial . From January 2000 until May 2005 , 93 patients with anorexia nervosa received intensive inpatient or day-program treatment at the New York State Psychiatric Institute or Toronto General Hospital . Participants regained weight to a minimum body mass index ( calculated as weight in kilograms divided by the square of height in meters ) of 19.0 and were then eligible to participate in the r and omized phase of the trial . INTERVENTIONS Participants were r and omly assigned to receive fluoxetine or placebo and were treated for up to 1 year as out patients in double-blind fashion . All patients also received individual cognitive behavioral therapy . MAIN OUTCOME MEASURES The primary outcome measures were time-to-relapse and the proportion of patients successfully completing 1 year of treatment . RESULTS Forty-nine patients were assigned to fluoxetine and 44 to placebo . Similar percentages of patients assigned to fluoxetine and to placebo maintained a body mass index of at least 18.5 and remained in the study for 52 weeks ( fluoxetine , 26.5 % ; placebo , 31.5 % ; P = .57 ) . In a Cox proportional hazards analysis , with prer and omization body mass index , site , and diagnostic subtype as covariates , there was no significant difference between fluoxetine and placebo in time-to-relapse ( hazard ratio , 1.12 ; 95 % CI , 0.65 - 2.01 ; P = .64 ) . CONCLUSIONS This study failed to demonstrate any benefit from fluoxetine in the treatment of patients with anorexia nervosa following weight restoration . Future efforts should focus on developing new models to underst and the persistence of this illness and on exploring new psychological and pharmacological treatment approaches . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00288574 Women who were referred with an eating disorder ( ED ) were compared with a matched normal control group to answer the following questions : What are the frequencies of anxiety disorders in cases of anorexia and bulimia nervosa diagnosed according to DSM-IV criteria ? Are anxiety disorders significantly more frequent among women with an eating disorder than among women from the community ? We assessed the frequencies of six specific anxiety disorders among 271 women with a current diagnosis of anorexia or bulimia nervosa and 271 controls , using the Mini-International Neuropsychiatric Interview , French DSM-IV version . A lifetime comorbidity with at least one anxiety disorder was found in 71 % of both the anorexic and the bulimic subjects , significantly higher than the percentage of controls with an anxiety disorder . The prevalence was significantly higher in the eating disorder groups than in controls for most types of anxiety disorder , and between 41.8 and 53.3 % of comorbid cases had an anxiety disorder preceding the onset of the eating disorder . Anxiety disorders are significantly more frequent in subjects with eating disorders than in volunteers from the community , a finding that has important etiological and therapeutic implication OBJECTIVE The aim of this study was to compare two maintenance treatment conditions for weight-restored anorexia nervosa ( AN ) : individual cognitive behavior therapy ( CBT ) and maintenance treatment as usual ( MTAU ) . METHOD This study was a nonr and omized clinical trial . The participants were 88 patients with AN who had achieved a minimum body mass index ( BMI ) of 19.5 and control of binge eating and purging symptoms after completing a specialized hospital-based program . Forty-six patients received 1 year of manualized individual CBT and 42 were in an assessment -only control condition ( i.e. , MTAU ) for 1 year . This condition was intended to mirror follow-up care as usual . Participants in both the conditions were assessed at 3-month intervals during the 1-year study . The main outcome variable was time to relapse . RESULTS When relapse was defined as a BMI < or= 17.5 for 3 months or the resumption of regular binge eating and /or purging behavior for 3 months , time to relapse was significantly longer in the CBT condition when compared with MTAU . At 1 year , 65 % of the CBT group and 34 % of the MTAU group had not relapsed . DISCUSSION The current findings provide preliminary evidence that CBT may be helpful in improving outcome and preventing relapse in weight-restored AN Background This study compared the best available treatment for bulimia nervosa , cognitive – behavioural therapy ( CBT ) augmented by fluoxetine if indicated , with a stepped-care treatment approach in order to enhance treatment effectiveness . Aims To establish the relative effectiveness of these two approaches . Method This was a r and omised trial conducted at four clinical centres ( Clinical trials.gov registration number : NCT00733525 ) . A total of 293 participants with bulimia nervosa were r and omised to one of two treatment conditions : manual-based CBT delivered in an individual therapy format involving 20 sessions over 18 weeks and participants who were predicted to be non-responders after 6 sessions of CBT had fluoxetine added to treatment ; or a stepped-care approach that began with supervised self-help , with the addition of fluoxetine in participants who were predicted to be non-responders after six sessions , followed by CBT for those who failed to achieve abstinence with self-help and medication management . Results Both in the intent-to-treat and completer sample s , there were no differences between the two treatment conditions in inducing recovery ( no binge eating or purging behaviours for 28 days ) or remission ( no longer meeting DSM – IV criteria ) . At the end of 1-year follow-up , the stepped-care condition was significantly superior to CBT . Conclusions Therapist-assisted self-help was an effective first-level treatment in the stepped-care sequence , and the full sequence was more effective than CBT suggesting that treatment is enhanced with a more individualised approach OBJECTIVE To date no trial has focused on the treatment of adolescents with bulimia nervosa . The aim of this study was to compare the efficacy and cost-effectiveness of family therapy and cognitive behavior therapy ( CBT ) guided self-care in adolescents with bulimia nervosa or eating disorder not otherwise specified . METHOD Eighty-five adolescents with bulimia nervosa or eating disorder not otherwise specified were recruited from eating disorder services in the United Kingdom . Participants were r and omly assigned to family therapy for bulimia nervosa or individual CBT guided self-care supported by a health professional . The primary outcome measures were abstinence from binge-eating and vomiting , as assessed by interview at end of treatment ( 6 months ) and again at 12 months . Secondary outcome measures included other bulimic symptoms and cost of care . RESULTS Of the 85 study participants , 41 were assigned to family therapy and 44 to CBT guided self-care . At 6 months , bingeing had undergone a significantly greater reduction in the guided self-care group than in the family therapy group ; however , this difference disappeared at 12 months . There were no other differences between groups in behavioral or attitudinal eating disorder symptoms . The direct cost of treatment was lower for guided self-care than for family therapy . The two treatments did not differ in other cost categories . CONCLUSIONS Compared with family therapy , CBT guided self-care has the slight advantage of offering a more rapid reduction of bingeing , lower cost , and greater acceptability for adolescents with bulimia or eating disorder not otherwise specified OBJECTIVE To collect nationally representative epidemiological data on early-onset eating disorders ( EOEDs ) in children . DESIGN Prospect i ve , active surveillance using the Australian Paediatric Surveillance Unit with key informant design . SETTING Child health specialists in Australia ( July 2002 to June 2005 ) . PATIENTS Incident cases of EOEDs in children aged 5 - 13 years . MAIN OUTCOME MEASURES Disease rates , demographic characteristics , clinical features and complications , hospitalisation , psychological comorbidity , and concordance of clinical features with Diagnostic and statistical manual of mental disorders , fourth edition ( DSM-IV ) criteria . RESULTS We identified 101 children aged 5 - 13 years with EOEDs ( median age , 12.2 years ; range , 5.5 - 13.9 years ) , of whom one in four were boys . Most were hospitalised ( 78 % ) , and the mean duration of hospitalisation was 24.7 days ( range , 1 - 75 days ) . More than 70 % of in patients were admitted to specialised eating disorder units in paediatric teaching hospitals . Among in patients , 37 % met DSM-IV diagnostic criteria for anorexia nervosa ; although 61 % had life-threatening complications of malnutrition , only 51 % met weight criteria . Psychological symptoms were similar to those in adults with anorexia nervosa : 67 % of in patients met both psychological diagnostic criteria for anorexia nervosa ( fear of weight gain/fatness and misperception of body shape ) . Of 19 postmenarchal girls , 18 had secondary amenorrhoea . Nasogastric feeding was used in 58 % of in patients , and 34 % received psychotropic medications . CONCLUSIONS This is the first prospect i ve national study of EOEDs . It demonstrates the limitations of applying DSM-IV diagnostic criteria for anorexia nervosa to young children ; the high proportion of boys affected by EOEDs ; and the significant psychological comorbidity and high frequency of hospitalisation associated with EOEDs . Potentially life-threatening medical complications are common at presentation , suggesting possible missed diagnoses and a need for education of health professionals . The study underlines the severity of EOEDs and the need for joint medical and psychiatric specialist management CONTEXT Evidence d-based treatment trials for adolescents with bulimia nervosa are largely absent . OBJECTIVE To evaluate the relative efficacy of family-based treatment ( FBT ) and supportive psychotherapy ( SPT ) for adolescents with bulimia nervosa . DESIGN R and omized controlled trial . SETTING The University of Chicago from April 1 , 2001 , through June 30 , 2006 . PARTICIPANTS Eighty patients , aged 12 to 19 years , with a DSM-IV diagnosis of bulimia nervosa or a strict definition of partial bulimia nervosa . INTERVENTIONS Twenty outpatient visits over 6 months of FBT or SPT . Participants were followed up at 6 months posttreatment . MAIN OUTCOME MEASURES Abstinence from binge- and -purge episodes as measured by the Eating Disorder Examination . Secondary outcome measures were Eating Disorder Examination binge- and -purge frequency and Eating Disorder Examination subscale scores . RESULTS Forty-one patients were assigned to FBT and 39 to SPT . Categorical outcomes at posttreatment demonstrated that significantly more patients receiving FBT ( 16 [ 39 % ] ) were binge- and -purge abstinent compared with those receiving SPT ( 7 [ 18 % ] ) ( P = .049 ) . Somewhat fewer patients were abstinent at the 6-month follow-up ; however , the difference was statistically in favor of FBT vs SPT ( 12 patients [ 29 % ] vs 4 patients [ 10 % ] ; P = .05 ) . Secondary outcome assessment , based on r and om regression analysis , revealed main effects in favor of FBT on all measures of eating pathological features ( P = .003 to P = .03 for all ) . CONCLUSIONS Family-based treatment showed a clinical and statistical advantage over SPT at posttreatment and at 6-month follow-up . Reduction in core bulimic symptoms was also more immediate for patients receiving FBT vs SPT Recently hospitalized bipolar , manic patients ( N = 53 ) were r and omly assigned to a 9-month , manual-based , family-focused psychoeducational therapy ( n = 28 ) or to an individually focused patient treatment ( n = 25 ) . All patients received concurrent treatment with mood-stabilizing medications . Structured follow-up assessment s were conducted at 3-month intervals for a 1-year period ofactive treatment and a 1-year period of posttreatment follow-up . Compared with patients in individual therapy , those in family-focused treatment were less likely to be rehospitalized during the 2-year study period . Patients in family treatment also experienced fewer mood disorder relapses over the 2 years , although they did not differ from patients in individual treatment in their likelihood of a first relapse . Results suggest that family psychoeducational treatment is a useful adjunct to pharmacotherapy in decreasing the risk of relapse and hospitalization frequently associated with bipolar disorder Recovered recurrently depressed patients were r and omized to treatment as usual ( TAU ) or TAU plus mindfulness-based cognitive therapy ( MBCT ) . Replicating previous findings , MBCT reduced relapse from 78 % to 36 % in 55 patients with 3 or more previous episodes ; but in 18 patients with only 2 ( recent ) episodes corresponding figures were 20 % and 50 % . MBCT was most effective in preventing relapses not preceded by life events . Relapses were more often associated with significant life events in the 2-episode group . This group also reported less childhood adversity and later first depression onset than the 3-or-more Output:	Bulimia nervosa ( BN ) received the most attention in the treatment literature , with cognitive behavioural therapy ( CBT ) and antidepressants the most common interventions . For anorexia nervosa ( AN ) , family based therapy ( FBT ) was the most studied .
MS21921	*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 recent recognition that coronary-artery stenting has improved the short- and long-term outcomes of patients treated with angioplasty has made it necessary to reevaluate the relative benefits of bypass surgery and percutaneous interventions in patients with multivessel disease . METHODS A total of 1205 patients were r and omly assigned to undergo stent implantation or bypass surgery when a cardiac surgeon and an interventional cardiologist agreed that the same extent of revascularization could be achieved by either technique . The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at one year . The costs of hospital re sources used were also determined . RESULTS At one year , there was no significant difference between the two groups in terms of the rates of death , stroke , or myocardial infa rct ion . Among patients who survived without a stroke or a myocardial infa rct ion , 16.8 percent of those in the stenting group underwent a second revascularization , as compared with 3.5 percent of those in the surgery group . The rate of event-free survival at one year was 73.8 percent among the patients who received stents and 87.8 percent among those who underwent bypass surgery ( P<0.001 by the log-rank test ) . The costs for the initial procedure were $ 4,212 less for patients assigned to stenting than for those assigned to bypass surgery , but this difference was reduced during follow-up because of the increased need for repeated revascularization ; after one year , the net difference in favor of stenting was estimated to be $ 2,973 per patient . CONCLUSION As measured one year after the procedure , coronary stenting for multivessel disease is less expensive than bypass surgery and offers the same degree of protection against death , stroke , and myocardial infa rct ion . However , stenting is associated with a greater need for repeated revascularization Background —This investigation compares the results of contemporary percutaneous coronary intervention ( PCI ) with st and ard balloon angioplasty among patients with multivessel coronary disease . Patients having balloon angioplasty in the Bypass Angioplasty Revascularization Investigation ( BARI ) and those within the Dynamic Registry meeting BARI eligibility criteria were studied . Methods and Results — Clinical features and in-hospital and 1-year outcomes of 857 BARI-eligible patients in the Dynamic Registry ( contemporary PCI ) were compared with the 904 r and omized patients who underwent percutaneous transluminal coronary angioplasty in BARI . Compared with BARI patients , Registry patients had fewer lesions attempted ( 1.53 versus 2.56 , P = 0.001 ) , more frequent single-vessel PCI ( 76 % versus 33 % , P < 0.001 ) , greater use of intracoronary stents ( 76 % versus 1 % , P < 0.001 ) , and GP IIb/IIIa receptor antagonist ( 24 % versus 0 % , P < 0.001 ) . Angiographic success was achieved more often among Registry patients ( 91 % versus 72 % , P < 0.001 ) , whereas abrupt closure ( 1.5 % versus 9.5 % , P < 0.001 ) and in-hospital coronary artery bypass graft ( CABG ) ( 1.9 % versus 10.2 % , P < 0.001 ) and myocardial infa rct ion ( 0.8 % versus 2.1 % , P = 0.025 ) were less common . No differences were observed in either in-hospital or 1-year death , but 1-year death/myocardial infa rct ion was lower in the Registry . Registry patients had lower 1-year rates of subsequent CABG ( 8.6 % versus 22.7 % , P < 0.001 ) and PCI ( 12.4 % versus 22.5 % , P < 0.001 ) . By multivariate analysis , contemporary PCI was independently associated with reduced risk for in-hospital CABG , 1-year CABG , and 1-year PCI . Conclusions —Among patients with multivessel disease , contemporary PCI result ed in safer and more durable revascularization . These results support the role of PCI for selected patients with multivessel coronary artery disease OBJECTIVES To compare the clinical - and cost-effectiveness of minimally invasive direct coronary artery bypass grafting ( MIDCAB ) and percutaneous transluminal coronary angioplasty ( PTCA ) with or without stenting in patients with single-vessel disease of the left anterior descending coronary artery ( LAD ) . DESIGN Multi-centre r and omised trial without blinding . The computer-generated sequence of r and omised assignments was stratified by centre , allocated participants in blocks and was concealed using a central ised telephone facility . SETTING Four tertiary cardiothoracic surgery centres in Engl and . PARTICIPANTS Patients with ischaemic heart disease with at least 50 % proximal stenosis of the LAD , suitable for either PTCA or MIDCAB , and with no significant disease in another vessel . INTERVENTIONS Patients r and omised to PTCA had local anaesthetic and underwent PTCA according to the method preferred by the operator carrying out the procedure . Patients r and omised to MIDCAB had general anaesthetic . The chest was opened through an 8 - 10-cm left anterior thoracotomy . The ribs were retracted and the left internal thoracic artery ( LITA ) harvested . The pericardium was opened in the line of the LAD to confirm the feasibility of operation . The distal LITA was anastomosed end-to-side to an arteriotomy in the LAD . All operators were experienced in carrying out MIDCAB . MAIN OUTCOME MEASURES The primary outcome measure was survival free from cardiac-related events . Relevant events were death , myocardial infa rct ion , repeat coronary revascularisation and recurrence of symptomatic angina or clinical signs of ischaemia during an exercise tolerance test at annual follow-up . Secondary outcome measures were complications , functional outcome , disease-specific and generic quality of life , health and social services re source use and their costs . RESULTS A total of 12,828 consecutive patients undergoing an angiogram were logged at participating centres from November 1999 to December 2001 . Of the 1091 patients with proximal stenosis of the LAD , 127 were eligible and consented to take part ; 100 were r and omised and the remaining 27 consented to follow-up . All r and omised participants were included in an intention-to-treat analysis of survival free from cardiac-related events , which found a non-significant benefit from MIDCAB . Cumulative hazard rates at 12 months were estimated to be 7.1 and 9.2 % for MIDCAB and PTCA , respectively . There were no important differences between MIDCAB and PTCA with respect to angina symptoms or disease-specific or generic quality of life . The total NHS procedure costs were 1648 British pounds and 946 British pounds for MIDCAB and PTCA , respectively . The costs of re sources used during 1 year of follow-up were 1033 British pounds and 843 British pounds , respectively . CONCLUSIONS The study found no evidence that MIDCAB was more effective than PTCA . The procedure costs of MIDCAB were observed to be considerably higher than those of PTCA . Given these findings , it is unlikely that MIDCAB represents a cost-effective use of re sources in the reference population . Recent advances in cardiac surgery mean that surgeons now tend to carry out off-pump bypass grafting via a sternotomy instead of MIDCAB . At the same time , cardiologists are treating more patients with multi-vessel disease by PTCA . Future primary research should focus on this comparison . Other small trials of PTCA versus MIDCAB have now finished and a more conclusive answer to the original objective could be provided by a systematic review Purpose : To compare percutaneous coronary intervention ( PCI ) using stent implantation versus coronary artery bypass graft ( CABG ) in patients with multiple vessel disease with involvement of the proximal left anterior descending coronary artery ( LAD ) . Methods : 230 patients with multiple vessel disease and severe stenosis of the proximal LAD ( 113 with PCI , 117 with CABG ) . They were a cohort of patients from the r and omised ERACI ( Argentine r and omized trial of percutaneous transluminal coronary angioplasty versus coronary artery bypass surgery in multivessel disease ) II study . Results : Both groups had similar baseline characteristics . There were no significant differences in 30 day major adverse cardiac events ( death , myocardial infa rct ion , stroke , and repeat procedures ) between the strategies ( PCI 2.7 % v CABG 7.6 % , p = 0.18 ) . There were no significant differences in survival ( PCI 96.4 % v CABG 95 % , p = 0.98 ) and survival with freedom from myocardial infa rct ion ( PCI 92 % v CABG 89 % , p = 0.94 ) at 41.5 ( 6 ) months ’ follow up . However , freedom from new revascularisation procedures ( CABG 96.6 % v PCI 73 % , p = 0.0002 ) and frequency of angina ( CABG 9.4 % v PCI 22 % , p = 0.025 ) were superior in the CABG group . Conclusion : Patients with multivessel disease and significant disease of the proximal LAD r and omly assigned in the ERACI II trial to PCI or CABG had similar survival and survival with freedom from myocardial infa rct ion at long term follow up . Repeat revascularisation procedures were higher in the PCI group Background —Our aims were to compare coronary artery bypass grafting ( CABG ) and stenting for the treatment of diabetic patients with multivessel coronary disease enrolled in the Arterial Revascularization Therapy Study ( ARTS ) trial and to determine the costs of these 2 treatment strategies . Methods and Results — Patients ( n=1205 ) were r and omly assigned to stent implantation ( n=600 ; diabetic , 112 ) or CABG ( n=605 ; diabetic , 96 ) . Costs per patient were calculated as the product of each patient ’s use of re sources and the corresponding unit costs . Baseline characteristics were similar between the groups . At 1 year , diabetic patients treated with stenting had the lowest event-free survival rate ( 63.4 % ) because of a higher incidence of repeat revascularization compared with both diabetic patients treated with CABG ( 84.4 % , P < 0.001 ) and nondiabetic patients treated with stents ( 76.2 % , P = 0.04 ) . Conversely , diabetic and nondiabetic patients experienced similar 1-year event-free survival rates when treated with CABG ( 84.4 % and 88.4 % ) . The total 1-year costs for stenting and CABG in diabetic patients were $ 12 855 and $ 16 585 ( P < 0.001 ) and in the nondiabetic groups , $ 10 164 for stenting and $ 13 082 for surgery . Conclusions —Multivessel diabetic patients treated with stenting had a worse 1-year outcome than patients assigned to CABG or nondiabetics treated with stenting . The strategy of stenting was less costly than CABG , however , regardless of diabetic status Background —Earlier reports have shown that the outcome of balloon angioplasty or bypass surgery in unstable angina is less favorable than in stable angina . Recent improvements in percutaneous treatment ( stent implantation ) and bypass surgery ( arterial grafts ) warrant reevaluation of the relative merits of either technique in treatment of unstable angina . Methods and Results —Seven hundred fifty-five patients with stable angina were r and omly assigned to coronary stenting ( 374 ) or bypass surgery ( 381 ) , and 450 patients with unstable angina were r and omly assigned to coronary stenting ( 226 ) or bypass surgery ( 224 ) . All patients had multivessel disease considered to be equally treatable by either technique . Freedom from major adverse events , including death , myocardial infa rct ion , and cerebrovascular events , at 1 year was not different in unstable patients ( 91.2 % versus 88.9 % ) and stable patients ( 90.4 % versus 92.6 % ) treated , respectively , with coronary stenting or bypass surgery . Freedom from repeat revascularization at 1 year was similar in unstable and stable angina treated with stenting ( 79.2 % versus 78.9 % ) or bypass surgery ( 96.3 % versus 96 % ) but was significantly higher in both unstable and stable patients treated with stenting ( 16.8 % versus 16.9 % ) compared with bypass surgery ( 3.6 % versus 3.5 % ) . Neither the difference in costs between stented or bypassed stable or unstable angina ( $ 2594 versus $ 3627 ) nor the cost-effectiveness was significantly different at 1 year . Conclusions —There was no difference in rates of death , myocardial infa rct ion , and cerebrovascular event at 1 year in patients with unstable angina and multivessel disease treated with either stented angioplasty or bypass surgery compared with patients Output:	No statistical differences were observed between CABG and stenting for meta- analysis of mortality or AMI , but there was heterogeneity . Composite cardiac event and revascularisation rates were lower for CABG than for stents . CABG is associated with reduced rates of major adverse cardiac events , mostly driven by reduced repeat revascularisation . Research on real-world patient population or patient level data meta-analyses may identify risk factors and groupings who may benefit most from one strategy over the other
MS21922	*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 The objective of this study was to determine whether reflexology has an impact on the quality of life of patients in the palliative stage of cancer . METHOD Twelve patients in the palliative stage of cancer with various tumour types were r and omised into two groups . They were r and omly assigned to receive either reflexology or placebo reflexology . All participants completed a linear analogue self- assessment scale relating to quality of life . All participants then received three sessions of either reflexology or placebo reflexology . The same person , a qualified reflexologist , provided the interventions for both groups . The participants were not aware of which intervention they were receiving . All participants then completed a second linear analogue self- assessment scale relating to quality of life . RESULTS All participants felt that their quality of life had improved , even those who had received the placebo treatment . The reflexology group , however , reported more benefit than the placebo group . There was a significant difference ( p = 0.004 ) between the reflexology group and the placebo group . CONCLUSION This study showed that reflexology does have an impact on the quality of life of patients in the palliative stage of cancer It is known that many patients with obstructive pulmonary diseases use a number of complementary and alternative medicines ( CAM ) . There has been a great deal of interest into the CAM recently , with the House of Lords select committee for science and technology 's report suggesting r and omised-controlled trials are the best means of research ing the area . There is very little research into the effects of reflexology specifically on the effects it has on COPD . As such a r and omised-controlled trial was set up to examine the effects of reflexology treatments on COPD . Results were qualitative and quantitative and showed that there are a number of areas of possible benefit for patients with COPD , but a larger scale study with a longer time frame is needed for a full evaluation of these effects Many specialist palliative care services are under pressure to provide therapies such as aromatherapy , acupuncture or reflexology either by paid staff or volunteers . The evidence to justify the provision of such treatment , however , remains largely anecdotal as controlled clinical trials are difficult to design . Reflexology involves the application of pressure to ` reflex ’ areas of the h and s or feet with the intention of producing specific effects elsewhere in the body . The reflexologist palpates tender or painful areas that , it is suggested , indicate functional imbalance . As well as treatment of specific conditions , it is suggested that reflexology can relax the patient , which may aid selfhealing and prevention of disease . We have therefore conducted a pilot study with a r and omized controlled design to compare reflexology with simple foot massage Integrative therapies such as massage have gained support as interventions that improve the overall patient experience during hospitalization . Cardiac surgery patients undergo long procedures and commonly have postoperative back and shoulder pain , anxiety , and tension . Given the promising effects of massage therapy for alleviation of pain , tension , and anxiety , we studied the efficacy and feasibility of massage therapy delivered in the postoperative cardiovascular surgery setting . Patients were r and omized to receive a massage or to have quiet relaxation time ( control ) . In total , 113 patients completed the study ( massage , n=62 ; control , n=51 ) . Patients receiving massage therapy had significantly decreased pain , anxiety , and tension . Patients were highly satisfied with the intervention , and no major barriers to implementing massage therapy were identified . Massage therapy may be an important component of the healing experience for patients after cardiovascular surgery The study aim ed to compare the effects of facial massage with that of foot massage on sleep induction and vital signs of healthy adults and to test a methodology that could be used by a lone research er in such a study . A r and omised within-group crossover pilot study of six healthy female volunteers was conducted . The interventions were a 20min foot and a 20min facial massage using peach-kernel base oil Prunus persica . A drop in systolic blood pressure of 8.5mmHg was recorded immediately after facial massage compared to that of 1mmHg recorded after foot massage . Both treatments were equally effective in reducing subjective levels of alertness during the interventions , with face massage marginally better at producing subjective sleepiness . A lone research er using these methods would be able objective ly to measure vital signs before and after interventions , but not during ; and would be able subjectively to measure sleep induction in non-sleep-laboratory context BACKGROUND Irritable bowel syndrome ( IBS ) is a significant problem for primary care , as treatment options are limited and it can frequently develop into a chronic condition . Complementary and alternative medicine , including reflexology , is being turned to increasingly in an attempt to manage symptoms . There are currently no studies which address the effectiveness of reflexology for IBS . Despite this , it continues to be advocated and used . AIM To provide the first evidence on the effectiveness of reflexology in the management of the core defining symptoms of IBS . DESIGN OF STUDY A single-blind trial carried out in primary care setting s. SETTING Thirty-four participants diagnosed with IBS on the basis of the Rome Criteria . METHOD Participants were allocated to receive either a reflexology foot massage or a non-reflexology foot massage control group . RESULTS On none of the three symptoms monitored -- abdominal pain , constipation/diarrhoea , and abdominal distention -- was there a statistically or clinical ly significant difference between reflexology and control groups . CONCLUSION On the basis of these results there is nothing to suggest that reflexology produces any specific benefit for patients with IBS . There is currently no evidence to support its use . However this was one ( relatively ) small scale study ; further research that , for example , assesses the impact of therapist ( professional and lay ) versus therapy , is still needed OBJECTIVE This experimental , repeated- measures , crossover design study with nursing home residents examined the efficacy of reflexology in individuals with mild-to-moderate stage dementia . Specifically , the study tested whether a weekly reflexology intervention contributed to the resident outcomes of reduced physiologic distress , reduced pain , and improved affect . SETTING The study was conducted at a large nursing home in suburban Philadelphia . SAMPLE The sample included 21 nursing home residents with mild-to-moderate stage dementia r and omly assigned to two groups . INTERVENTIONS The first group received 4 weeks of weekly reflexology treatments followed by 4 weeks of a control condition of friendly visits . The second group received 4 weeks of friendly visits followed by 4 weeks of weekly reflexology . OUTCOME MEASURES The primary efficacy endpoint was reduction of physiologic distress as measured by salivary alpha-amylase . The secondary outcomes were observed pain ( Checklist of Nonverbal Pain Indicators ) and observed affect ( Apparent Affect Rating Scale ) . RESULTS The findings demonstrate that when receiving the reflexology treatment condition , as compared to the control condition , the residents demonstrated significant reduction in observed pain and salivary alpha-amylase . No adverse events were recorded during the study period . CONCLUSIONS This study provides preliminary support for the efficacy of reflexology as a treatment of stress in nursing home residents with mild-to-moderate stage dementia OBJECTIVE To determine whether foot reflexology , a complementary therapy , has an effect greater than sham reflexology on induction of ovulation . DESIGN Sham-controlled r and omized trial with patients and statistician blinded . SETTING Infertility clinic in Plymouth , United Kingdom . PATIENT(S ) Forty-eight women attending the clinic with anovulation . INTERVENTION(S ) Women were r and omized to receive eight sessions of either genuine foot reflexology or sham reflexology with gentle massage over 10 weeks . MAIN OUTCOME MEASURE(S ) The primary outcome was ovulation detected by serum progesterone level of > 30 nmol/L during the study period . RESULT ( S ) Twenty-six patients were r and omized to genuine reflexology and 22 to sham ( one r and omized patient was withdrawn ) . Patients remained blinded throughout the trial . The rate of ovulation during true reflexology was 11 out of 26 ( 42 % ) , and during sham reflexology it was 10 out of 22 ( 46 % ) . Pregnancy rates were 4 out of 26 in the true group and 2 out of 22 in the control group . Because of recruitment difficulties , the required sample size of 104 women was not achieved . CONCLUSION ( S ) Patient blinding of reflexology studies is feasible . Although this study was too small to reach a definitive conclusion on the specific effect of foot reflexology , the results suggest that any effect on ovulation would not be clinical ly relevant . Sham reflexology may have a beneficial general effect , which this study was not design ed to detect OBJECTIVE To evaluate the effect of reflexology on symptoms of multiple sclerosis ( MS ) in a r and omized , sham-controlled clinical trial . METHODS Seventy-one MS patients were r and omized to either study or control group , to receive an 11-week treatment . Reflexology treatment included manual pressure on specific points in the feet and massage of the calf area . The control group received nonspecific massage of the calf area . The intensity of paresthesias , urinary symptoms , muscle strength and spasticity was assessed in a masked fashion at the beginning of the study , after 1.5 months of treatment , end of study and at three months of follow-up . RESULTS Fifty-three patients completed this study . Significant improvement in the differences in mean scores of paresthesias ( P = 0.01 ) , urinary symptoms ( P = 0.03 ) and spasticity ( P = 0.03 ) was detected in the reflexology group . Improvement with borderline significance was observed in the differences in mean scores of muscle strength between the reflexology group and the controls ( P = 0.06 ) . The improvement in the intensity of paresthesias remained significant at three months of follow-up ( P = 0.04 ) . CONCLUSIONS Specific reflexology treatment was of benefit in alleviating motor ; sensory and urinary symptoms in MS patients OBJECTIVE An influence on organ-associated blood flow is considered as a possible mechanism of action of reflex zone massage of the feet ( FRZM ) therapy . In the present study we investigated whether changes in intestinal blood flow can be achieved by FRZM . MATERIAL AND METHODS 32 healthy adults ( 19 women and 13 men ) were r and omly assigned to the treatment or the placebo group . Subjects of the treatment group received foot massage on the zones assigned to the intestines and those of the placebo group received massage on zones unrelated to the intestines . Before , during and after FRZM , the blood flow velocity , the peak systolic and the end diastolic velocities in the superior mesenteric artery as well as the resistive index as a parameter of vascular resistance were calculated . RESULTS During FRZM , in the subjects of the treatment group there was a significant reduction in the resistive index ( p = 0.021 ) , suggesting an increase in the blood flow in the superior mesenteric artery and the subordinate vascular system . In contrast , there were no significant changes in the resistive index in the subjects of the placebo group . CONCLUSION The reduction in the resistive index observed in the treatment group supports the assumption that FRZM improves blood flow in the organs considered to be associated with the specific foot zones , at least during the therapy process Objective : To determine whether reflexology therapy — the application of manual pressure to reflex points on the ears , h and s , and feet that somatotopically correspond to specific areas of the body — can significantly reduce premenstrual symptoms compared to placebo treatment . Methods : Thirty-five women who complained of previous distress with premenstrual syndrome ( PMS ) were r and omly assigned to be treated by ear , h and , and foot reflexology or to receive placebo reflexology . All subjects completed a daily diary , which monitored 38 premenstrual symptoms on a four-point scale . Somatic and psychological indicators of premenstrual distress were recorded each day for 2 months before treatment , for 2 months during reflexology , and for 2 months afterward . The reflexology sessions for both groups were provided by a trained reflexology therapist once a week for 8 weeks , and lasted 30 minutes each . Results : Analysis of variance for repeated measures demonstrated a significantly greater decrease in premenstrual symptoms for the women given true reflexology treatment than for the women in the placebo group . Conclusion : These clinical findings support the use of ear , h and , and foot reflexology for the treatment of PMS Critical care can be considered to be a stressful environment at both physiological and psychological levels for patients . In this article , a research study in which a five-minute foot massage was offered to 25 patients ( 68 sessions in total ) as a stress-reduction intervention is described . A quasi-experimental repeated measures design was used to collect data before , during and after the intervention . Physiological data ( heart rate , mean arterial blood pressure , respirations and peripheral oxygen saturation ) were obtained from the patient bedside monitoring system . Repeated measures analysis of variance indicated there was no significant effect from the intervention on peripheral oxygen saturation . However , a significant decrease in heart rate , blood pressure and respirations was observed during the foot massage intervention . Results indicated foot massage had the potential effect of increasing relaxation as evidence d by physiological changes during the brief intervention administered to critically ill patients in intensive care Objective Clinical experience suggests that reflexology may have beneficial effects on the symptoms occurring in menopausal women , particularly psychological symptoms . This study aims to examine that effect rigorously BACKGROUND Because of the widely presumed association between heart disease and psychological wellbeing , the use of so-called ' complementary ' therapies as adjuncts to conventional treatment modalities have been the subject of considerable debate . The present study arose from an attempt to identify a safe and effective therapeutic intervention to promote wellbe ing , which could be practicably delivered by nurses to patients in the postoperative recovery period following Output:	This systematic review found that although reflexology has been shown to have an effect on selected hemodynamic variables , the lack of method ological control for nonspecific general massage effects means that there is little convincing evidence at this time to suggest the existence of a specific treatment-related hemodynamic effect . Furthermore , the review found that few studies of reflexology controlled for nonspecific effects in order to isolate any specific active component , despite the hemodynamic cl aim being a key part of the therapeutic value of reflexology .
MS21923	*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 attributable cost of ventilator-associated pneumonia from a hospital-based cost perspective , after adjusting for potential confounders . Design Patients admitted between January 19 , 1998 , and December 31 , 1999 , were followed prospect ively for the occurrence of ventilator-associated pneumonia . Hospital costs were defined by using the hospital cost accounting data base . Setting The medical and surgical intensive care units at a suburban , tertiary care hospital . Patients Patients requiring > 24 hrs of mechanical ventilation . Interventions None . Measurements and Main Results We measured occurrence of ventilator-associated pneumonia , in-hospital mortality rate , total intensive care unit ( ICU ) and hospital lengths of stay ( LOS ) , and total hospital cost per patient . Ventilator-associated pneumonia occurred in 127 of 819 patients ( 15.5 % ) . Compared with uninfected , ventilated patients , patients with ventilator-associated pneumonia had a higher Acute Physiology and Chronic Health Evaluation II score on admission ( p < .001 ) and were more likely to require multiple intubations ( p < .001 ) , hemodialysis ( p < .001 ) , tracheostomy ( p < .001 ) , central venous catheters ( p < .001 ) , and corticosteroids ( p < .001 ) . Patients with ventilator-associated pneumonia were more likely to be bacteremic during their ICU stay ( 36 [ 28 % ] vs. 22 [3%];p < .001 ) . Patients with ventilator-associated pneumonia had significantly higher unadjusted ICU LOS ( 26 vs. 4 days;p < .001 ) , hospital LOS ( 38 vs. 13 days;p < .001 ) , mortality rate ( 64 [ 50 % ] vs. 237 [34%];p < .001 ) , and hospital costs ( $ 70,568 vs. $ 21,620 , p < .001 ) . Multiple linear regression , controlling for other factors that may affect costs , estimated the attributable cost of ventilator-associated pneumonia to be $ 11,897 ( 95 % confidence interval = $ 5,265–$26,214;p < .001 ) . Conclusions Patients with ventilator-associated pneumonia had significantly longer ICU and hospital LOS , with higher crude hospital cost and mortality rate compared with uninfected patients . After we adjusted for underlying severity of illness , the attributable cost of ventilator-associated pneumonia was approximately $ 11,897 Objective : To evaluate the effect of a method of Selective Decontamination of the Digestive Tract ( SDD ) on colonization , nosocomial infection ( NI ) , bacterial resistance , mortality and economic costs . Design : R and omized , double blind , placebo controlled study . Setting : Polyvalent intensive care unit ( ICU ) of a tertiary care hospital with 27 beds . Patients : 101 patients with > 3 days of mechanical ventilation and > 5 days of stay , without infection at the start of the study . 47 belonged to the Treated Group ( TG ) and 54 to the Placebo Group ( PG ) . Interventions : The TG was given Cefotaxime i.v . ( 6 g/day ) for the first four days and an association of Polymyxin E , Tobramycin and Amphothericin B at the oropharyngeal and gastrointestinal level throughout the whole stay . Results : In the TG , colonization by gram-negative agents at oropharyngeal , tracheal and gastrointestinal level fell significantly . There was a significant drop in the overall , respiratory and urinary NI ( 26 % vs 63%,p<0.001 ; 15 % vs 46%,p<0.001 ; 9 % vs 31%,p<0.01 ) . The overall mortality and NI related mortality was less in the TG ( 21 % vs 44%,p<0.05 ; 2 % vs 20%,p<0.01 ) . The economic costs , mechanical ventilation time and length of stay were similar . The percentage of bacterial isolations resistant to Cefotaxime and Tobramycin was greater in the TG ( 38 % vs 15 % and 38 % vs 9%,p<0.001 ) . Conclusions : colonization by gram-negative bacilli , NI and the mortality related to it can be modified by SDD . Continuous bacteriological surveillance is necessary BACKGROUND The purpose of this study was to compare the performance of heat and moisture exchanger filters with heated humidifying systems in the mechanical ventilator circuit on the incidence of ventilator-associated pneumonia ( VAP ) and bacterial colonization . METHOD Two hundred and forty-three consecutive patients who required mechanical ventilation for 48 hours or more in the adult intensive care unit were r and omized to either a heat and moisture exchanger ( HME ) or a heated humidifying breathing circuit . RESULTS The VAP rate among the group with HME was 11.4 % ; the rate among the group with heated humidifying system ( HHS ) was 15.8 % . The difference was not statistically significant . Approximately 68 % of the patients in the HME group had no pathogen isolated compared with 50 % of the patients in the HHS group . This difference was statistically significant ( P = .006 ) . However , the distribution of the pathogens among those patients who had the isolated pathogens was mostly identical in the 2 groups . CONCLUSION Even though the study did not find HME to be significantly advantageous over the HHS , in as much as VAP rate is concerned , other advantages such as reduced nurses workload , reduced financial cost , and better safety made HME a more favorable device for use in our adult intensive care unit STUDY OBJECTIVE To determine the cost-effectiveness of continuous subglottic suctioning ( CSS ) as a strategy to decrease the incidence of ventilator-associated pneumonia ( VAP ) . DESIGN Decision-model analysis of the cost and efficacy of endotracheal tubes that allow CSS at preventing VAP . The primary outcome was cases of VAP averted . Model estimates were based on data from published prospect i ve trials of CSS and other prospect i ve studies of the incidence of VAP . SETTING AND PATIENTS Hypothetical cohort of 100 patients requiring nonelective endotracheal intubation and management in an ICU . INTERVENTIONS In the model , patients were managed with either traditional endotracheal tubes ( ETs ) or ETs capable of CSS . MEASUREMENTS AND MAIN RESULTS The marginal cost-effectiveness of CSS was calculated as the savings result ing from cases of VAP averted minus the additional costs of CSS-ETs , and expressed as cost ( or savings ) per episode of VAP prevented . Sensitivity analysis of the impact of the major clinical inputs on the cost-effectiveness was performed . The base case assumed that the incidence of VAP in patients requiring > 72 h of mechanical ventilation ( MV ) was 25 % , that CSS-ETs had no impact on patients requiring MV for < 72 h , and that CSS-ETs result ed in a relative risk reduction of VAP of 30 % . Despite the higher costs of ETs capable of CSS , this tactic yielded a net savings of $ 4,992 per case of VAP prevented . For sensitivity analysis , model inputs were adjusted by 50 % individually and then simultaneously . This demonstrated the model to be only moderately sensitive to the calculated cost of VAP . With the relative risk reduction at 50 % of the base-case estimate , CSS result ed in $ 1,924 saved per case of VAP prevented . When all variables were skewed against CSS , total outlays were trivial ( approximately $ 14 per patient in the cohort ) . CONCLUSIONS CSS represents a strategy for the prevention of VAP that may result in savings . Further studies are warranted to confirm the efficacy of CSS Risk factors for the development of ventilator-associated pneumonia ( VAP ) , as identified in epidemiological studies , have provided a basis for testable interventions in r and omized trials . We describe how these results have influenced patient treatment . Single interventions in patients undergoing intubation have focused on either reducing aspiration of oropharyngeal secretions , modulation of colonization ( in either the oropharynx , the stomach , or the whole digestive tract ) , use of systemic antimicrobial prophylaxis , or ventilator circuit changes . More recently , multiple simultaneously implemented interventions have been used . In general , routine measures to decrease oropharyngeal aspiration and antibiotic-containing prevention strategies appear to be the most effective , and the latter were associated with improved rates of patient survival in recent trials . These benefits must be balanced against the widespread fear of emergence of antibiotic resistance . In hospital setting s with low baseline levels of antibiotic resistance , however , the benefits to patient outcome may outweigh this fear of resistance . In setting s with high levels of antibiotic resistance , combined approaches of non-antibiotic using strategies and education programs might be most beneficial STUDY OBJECTIVE To compare the clinical outcomes of critically ill patients developing early-onset nosocomial pneumonia ( NP ; ie , within 96 h of ICU admission ) and late-onset NP ( ie , occurring after 96 h of ICU admission ) . DESIGN Prospect i ve cohort study . SETTING A medical ICU and a surgical ICU from a university-affiliated urban teaching hospital . PATIENTS Between July 1997 and November 1998 , 3 , 668 patients were prospect ively evaluated . INTERVENTION Prospect i ve patient surveillance and data collection . RESULTS Four hundred twenty patients ( 11.5 % ) developed NP . Early-onset NP was observed in 235 patients ( 56.0 % ) , whereas 185 patients ( 44.0 % ) developed late-onset NP . Among patients with early onset NP , 114 patients ( 48 . 5 % ) spent at least 24 h in the hospital prior to ICU admission , compared to 57 patients ( 30.8 % ) with late-onset NP ( p = 0.001 ) . One hundred eighty-three patients ( 77.9 % ) with early-onset NP received antibiotics prior to the development of NP , as compared to 162 patients ( 87.6 % ) with late-onset NP ( p = 0.010 ) . The most common pathogens associated with early-onset NP were Pseudomonas aeruginosa ( 25.1 % ) , oxacillin-sensitive Staphylococcus aureus ( OSSA ; 17.9 % ) , oxacillin-resistant S aureus ( ORSA ; 17.9 % ) , and Enterobacter species ( 10.2 % ) . P aeruginosa ( 38.4 % ) , ORSA ( 21.1 % ) , Stenotrophomonas maltophilia ( 11.4 % ) , OSSA ( 10.8 % ) , and Enterobacter species ( 10.3 % ) were the most common pathogens associated with late-onset NP . The ICU length of stay was significantly longer for patients with early-onset NP ( 10.3 + /- 8.3 days ; p < 0.001 ) and late-onset NP ( 21 . 0 + /- 13.7 days ; p < 0.001 ) , as compared to patients without NP ( 3.5 + /- 3.2 days ) . Hospital mortality was significantly greater for patients with early-onset NP ( 37.9 % ; p = 0.001 ) and late-onset NP ( 41.1 % ; p = 0.001 ) compared to patients without NP ( 13.1 % ) . CONCLUSIONS Both early-onset and late-onset NP are associated with increased hospital mortality rates and prolonged lengths of stay . The pathogens associated with NP were similar for both groups . This may be due , in part , to the prior hospitalization and use of antibiotics in many patients developing early-onset NP . These data suggest that P aeruginosa and ORSA can be important pathogens associated with early-onset NP in the ICU setting . Additionally , clinicians should be aware of the common microorganisms associated with both early-onset NP and late-onset NP in their hospitals in order to avoid the administration of inadequate antimicrobial treatment Nosocomial pneumonia is the leading cause of death among all hospital-acquired infections [ 1 ] . The estimated incidence of nosocomial pneumonia in intensive care units ranges from 10 % to 65 % ; most studies [ 2 - 6 ] show case fatality rates of more than 20 % . Ventilator-associated pneumonia specifically refers to nosocomial pneumonia that develops in a mechanically ventilated patient and that was not present at the time of airway intubation [ 7 ] . Various clinical risk factors have been associated with an increased incidence of ventilator-associated pneumonia , either because they predispose the patient to bacterial colonization of the oropharynx and stomach ( for example , the administration of antacids or histamine-2-receptor antagonists ) or because they facilitate aspiration of contaminated contents from these sites ( for example , supine positioning ) [ 1 , 2 , 8 , 9 ] . Craven and colleagues [ 10 ] first showed that the frequency of ventilator circuit changes also influences the incidence of ventilator-associated pneumonia . They found that changing circuits every 24 rather than every 48 hours was independently associated with the occurrence of nosocomial p Output:	CONCLUSIONS Ventilator-associated pneumonia occurs in a considerable proportion of patients undergoing mechanical ventilation and is associated with substantial morbidity , a two-fold mortality rate , and excess cost .
MS21924	*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 : Pharmacokinetic data suggests that the intravenous form of n‐acetylcysteine ( NAC ) may be more effective than the oral formulation in preventing contrast induced nephropathy ( CIN ) . NAC owing to its anti‐oxidant properties might be beneficial for patients with acute coronary syndromes ( ACS ) who are at increased risk for CIN . The aim of this prospect i ve r and omized , single‐center , double‐blind , placebo controlled trial ( NCT00939913 ) was to assess the effect of high‐dose intravenous NAC on CIN in ACS patients undergoing coronary angiography and /or percutaneous coronary intervention ( PCI ) . Methods : We r and omized 398 ACS patients scheduled for diagnostic angiography ± PCI to an intravenous regimen of high‐dose NAC ( 1,200 mg bolus followed by 200 mg/hr for 24 hr ; n = 206 ) or placebo ( n = 192 ) . The primary end‐point was incidence of CIN defined as an increase in serum creatinine concentration ≥25 % above the baseline level within 72 hr of the administration of intravenous contrast . Results : There was no difference found for the primary end point with CIN in 16 % of the NAC group and in 13 % of the placebo group ( p = 0.40 ) . Change in serum cystatin‐C , a sensitive marker for renal function , was 0.046 ± 0.204 in the NAC group and 0.002 ± 0.260 in the control group ( p = 0.07 ) . Conclusion : In ACS patients undergoing angiography ± PCI , high‐dose intravenous NAC failed to reduce the incidence of CIN . © 2011 Wiley Periodicals , BACKGROUND Contrast-induced nephropathy ( CIN ) is a leading cause of acute renal failure and affects mortality and morbidity . We investigated the efficacy of prophylactic intravenous ( IV ) N-acetylcysteine ( NAC ) and hydration for the prevention of CIN in patients with mild to moderate renal dysfunction who are undergoing coronary angiography and /or percutaneous coronary intervention ( PCI ) . METHODS A total of 220 patients who had mild to moderate renal dysfunction with serum creatinine ( SCr ) ≥ 1.1mg/dL or creatinine clearance ≤ 60 mL/min were r and omized in 3 groups : 80 patients were assigned to IV NAC plus high-dose hydration with normal saline , 80 patients to only high-dose hydration with normal saline and 60 patients to st and ard hydration with normal saline ( control group ) . The primary end point was the alteration of SCr level . The secondary end point was the development of CIN after the procedure . RESULTS SCr levels changed the least in the NAC plus high-hydration group ( P=0.004 ) . The rate of the CIN in the NAC plus high-dose hydration group was also lower than the high-dose hydration group ( P=0.006 ) . No significant differences in the primary and secondary end points were found between high-dose hydration and control group . CONCLUSION The results of this study suggest that NAC plus high-dose hydration was superior to high-dose hydration alone as well as st and ard hydration for the protection of renal functions in patients with mild to moderate renal dysfunction who are undergoing coronary angiography and /or PCI . High-dose hydration without NAC was not better than st and ard hydration alone OBJECTIVES Prophylactic acetylcysteine along with hydration seems to be better than hydration alone in preventing the reduction in renal function induced by a contrast dye . BACKGROUND Contrast media can lead to acute renal failure that may occasionally require hemodialysis . METHODS One hundred eighty-three consecutive patients with impairment of renal function , undergoing coronary and /or peripheral angiography and /or angioplasty , were r and omly assigned to receive 0.45 % saline intravenously and acetylcysteine ( 600 mg orally twice daily ; group A , n = 92 ) or 0.45 % saline intravenously alone ( group B , n = 91 ) before and after nonionic , low-osmolality contrast dye administration . RESULTS The baseline serum creatinine concentrations were similar ( 1.5 + /- 0.4 mg/dl in group A vs. 1.5 + /- 0.4 mg/dl in group B ; p = 0.37 ) . An increase of > or = 25 % in the baseline creatinine level 48 h after the procedure occurred in 6 ( 6.5 % ) of 92 patients in group A and in 10 ( 11 % ) of 91 patients in group B ( p = 0.22 ) . In the subgroup with a low ( < 140 ml ) contrast dose , renal function deterioration occurred in 5 ( 8.5 % ) of 60 patients in group B and in 0 of 60 patients in group A ( p = 0.02 ; odds ratio [ OR ] 0.44 , 95 % confidence interval [ CI ] 0.35 to 0.54 ) . In the subgroup with a high contrast dose , no difference was found ( 5/31 vs. 6/32 patients , p = 0.78 ) . By multivariate analysis , the amount of contrast agent , but not the treatment strategy , was a predictor of the occurrence of contrast dye-associated nephrotoxicity ( OR 2.58 , 95 % CI 1.1 to 4.9 ; p = 0.035 ) . CONCLUSIONS In patients with reduced renal function undergoing angiography and /or angioplasty , the amount of contrast agent , but not the administration of prophylactic acetylcysteine , was a predictor of renal function deterioration . Prophylactic acetylcysteine might provide better protection than hydration alone , only when a small volume of contrast agent is used BACKGROUND Contrast-induced nephropathy ( CIN ) after cardiac catheterization is common in patients with preexisting renal dysfunction . Studies of oral acetylcysteine to prevent CIN have produced conflicting results . Intravenous N-acetylcysteine ( NAC ) has logistic advantages in this setting . The objective of this study was to evaluate , in a blinded , r and omized , placebo-controlled fashion , whether intravenous NAC reduced CIN in the setting of cardiac catheterization in patients with preexisting renal insufficiency . METHODS Patients with renal dysfunction undergoing cardiac catheterization were r and omly assigned to intravenous NAC 500 mg immediately before the procedure or placebo . All patients received isotonic saline ( 200 mL ) beforeh and , followed by 1.5 mL/kg per hour for 6 hours , unless contraindicated . Exclusion criteria included acute renal failure , creatinine > 400 micromol/L , concurrent dialysis , unstable clinical status , and prior NAC use . Baseline creatinine was obtained immediately before the procedure and repeated 2 to 8 days later . The primary end point was the occurrence of CIN defined as a reduction in creatinine clearance from baseline of > 5 mL/min ( Cockcroft-Gault formula ) . RESULTS The study was terminated early because of a determination of futility by the Data Safety Monitoring Committee after enrollment of 487 patients . The median baseline creatinine clearance was 44 mL/min ( interquartile range , 33 , 55 ) . Median contrast received was 120 mL ( interquartile range , 80 , 175 ) . Baseline characteristics were similar in the two groups . Altogether , 98 ( 22.0 % ) subjects had the primary end point : 23.3 % in the NAC group and 20.7 % in the placebo arm ( P = .57 ) . CONCLUSIONS In this large , r and omized trial , enrolling a high-risk group of patients with impaired renal function , intravenous NAC was ineffective in preventing CIN OBJECTIVES The aim of this r and omized , single-blind , controlled trial was to assess N-acetylcysteine effects on contrast-induced nephropathy and reperfusion injury in ST-segment elevation myocardial infa rct ion patients undergoing primary angioplasty with moderate contrast volumes . BACKGROUND High-dose N-acetylcysteine reduced the incidence of contrast-induced nephropathy in patients with high contrast volumes and reduced reperfusion injury in animal trials . METHODS Patients undergoing primary angioplasty were r and omized to either high-dose N-acetylcysteine ( 2 x 1,200 mg/day for 48 h ; n = 126 ) or placebo plus optimal hydration ( n = 125 ) . The 2 primary end points were : 1 ) the occurrence of > 25 % increase in serum creatinine level < 72 h after r and omization ; and 2 ) a reduction in reperfusion injury measured as myocardial salvage index by magnetic resonance imaging . RESULTS The median volume of an iso-osmolar contrast agent during angiography was 180 ml ( interquartile range [ IQR ] 140 to 230 ml ) in the N-acetylcysteine and 160 ml ( IQR 120 to 220 ml ) in the placebo group ( p = 0.20 ) . The primary end point contrast-induced nephropathy occurred in 14 % of the N-acetylcysteine group and in 20 % of the placebo group ( p = 0.28 ) . The myocardial salvage index was also not different between both treatment groups ( 43.5 ; IQR 25.4 to 71.9 vs. 51.5 ; IQR 29.5 to 75.3 ; p = 0.36 ) . Activated oxygen protein products and oxidized low-density lipoprotein as markers for oxidative stress were reduced by as much as 20 % in the N-acetylcysteine group ( p < 0.05 ) , whereas no change was evident in the placebo group . CONCLUSIONS High-dose intravenous N-acetylcysteine reduces oxidative stress . However , it does not provide an additional clinical benefit to placebo with respect to CIN and myocardial reperfusion injury in nonselected patients undergoing angioplasty with moderate doses of contrast medium and optimal hydration . ( Myocardial Salvage and Contrast Dye Induced Nephropathy Reduction by N-Acetylcysteine [ LIPSIA-N-ACC ] ; NCT00463749 ) CONTEXT The antioxidant acetylcysteine prevents acute contrast nephrotoxicity in patients with impaired renal function who undergo computed tomography scanning . However , its role in coronary angiography is unclear . OBJECTIVE To determine whether oral acetylcysteine prevents acute deterioration in renal function in patients with moderate renal insufficiency who undergo elective coronary angiography . DESIGN AND SETTING Prospect i ve , r and omized , double-blind , placebo-controlled trial conducted from May 2000 to December 2001 at the Grantham Hospital at the University of Hong Kong . PARTICIPANTS Two hundred Chinese patients aged mean ( SD ) 68 ( 6.5 ) years with stable moderate renal insufficiency ( creatinine clearance < 60 mL/min [ 1.00 mL/s ] ) who were undergoing elective coronary angiography with or without intervention . INTERVENTION Participants were r and omly assigned to receive oral acetylcysteine(600 mg twice per day ; n = 102 ) or matching placebo tablets ( n = 98 ) on the day before and the day of angiography . All patients received low-osmolality contrast agent . MAIN OUTCOME MEASURES Occurrence of more than a 25 % increase in serum creatinine level within 48 hours after contrast administration ; change in creatinine clearance and serum creatinine level . RESULTS Twelve control patients ( 12 % ) and 4 acetylcysteine patients ( 4 % ) developed a more than 25 % increase in serum creatinine level within 48 hours after contrast administration ( relative risk , 0.32 ; 95 % confidence interval [ CI ] , 0.10 - 0.96 ; P = .03 ) . Serum creatinine was lower in the acetylcysteine group ( 1.22 mg/dL [ 107.8 micromol/L ] ; 95 % CI , 1.11 - 1.33 mg/dL vs 1.38 mg/dL [ 122.9 micromol/L ] ; 95 % CI , 1.27 - 1.49 mg/dL ; P = .006 ) during the first 48 hours after angiography . Acetylcysteine treatment significantly increased creatinine clearance from 44.8 mL/min ( 0.75 mL/s ) ( 95 % CI , 42.7 - 47.6 mL/min ) to 58.9 mL/min ( Output:	The results of the present paper support the use of NAC in the prevention of CIN in patients undergoing CAG±PCI .
MS21925	*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 WHO recommends that adults with uncomplicated P. falciparum successfully treated with a blood schizonticide receive a single dose of primaquine ( PQ ) 45 mg as a gametocytocidal agent . An earlier pilot study suggested that 75 mg of bulaquine ( BQ ) , of which PQ is a major metabolite , may be a useful alternate to PQ . Methods In a r and omized , partial blind study , 90 hospitalized adults with Plasmodium falciparum malaria that was blood schizonticide-responsive and a gametocytemia of > 55/μl within 3 days of diagnosis were r and omized to receive single doses of either PQ 45 mg or BQ 75 mg on day 4 . We assessed gametocytemia on days 8 , 15 , 22 and 29 and gametocyte viability as determined by exflagellation ( 2 ° end point ) on day 8 . Results On day 8 , 20/31 ( 65 % ) primaquine recipients versus 19/59 ( 32 % ) bulaquine recipients showed persistence of gametocytes ( P = 0.002 ) . At day 15 and beyond , all patients were gametocyte free . On day 8 , 16/31 PQ and 7/59 BQ volunteers showed gametocyte viability ( p = 0.000065 ) . Conclusion BQ is a safe , useful alternate to PQ as a Plasmodium falciparum gametocytocidal agent and may clear gametocytemia faster than PQ Abstract The prophylactic and sporontocidal efficacy of st and ard antimalarials was studied among non-immune adult male volunteers challenged by mosquitoes heavily infected with two strains of chloroquine resistant Plasmodium falciparum from Malaya . The Poo . strain from Trengganu broke through in 12 of 15 men receiving chloroquine 300 mg . ( base ) and primaquine 45 mg . ( base ) at weekly intervals , whereas 8 weeks of this treatment protected all 3 men challenged with the Tay . strain from Kota Tinggi , Johore State . The Poo . strain broke through in 5 men given amodiaquine base 300 mg . and DDS 300 mg . weekly . Proguanil 200 mg . ( 2·1–3·2 mg . per kg . body weight ) given daily for 8 weeks after challenge provided complete suppression of the Poo . strain in 4 men ( and probably a fifth ) , and also of the Tay . strain in 4 men , nor did parasitaemia develop after completion of the prophylactic course . Pyrimethamine 25 mg . given weekly failed to protect 2 of 3 men challenged with Poo . , and the Tay . strain also broke through in both men receiving this regimen . A single dose of 45 mg . ( base ) of primaquine was gametocytocidal for both strains and , in one case of Poo . infection studied , rendered gametocytes non-infective to an efficient vector mosquito fed on the patient 24 hours later ABSTRACT The current interest in malaria elimination has led to a renewed interest in drugs that can be used for mass administration to minimize malaria transmission . Primaquine ( PQ ) is the only generally available drug with a strong activity against mature Plasmodium falciparum gametocytes , the parasite stage responsible for transmission . Despite concerns about PQ-induced hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals , a single dose of PQ may be safe and efficacious in clearing gametocytes that persist after conventional treatment . As part of a mass drug intervention , we determined the hemolytic effect of sulfadoxine-pyrimethamine ( SP ) plus artesunate ( AS ) plus a single dose of primaquine ( PQ ; 0.75 mg/kg of body weight ) in children aged 1 to 12 years . Children were r and omized to receive SP+AS+PQ or placebo ; those with a hemoglobin ( Hb ) level below 8 g/dl were excluded from receiving PQ and received SP+AS . The Hb concentration was significantly reduced 7 days after SP+AS+PQ treatment but not after placebo or SP+AS treatment . This reduction in Hb was most pronounced in G6PD-deficient ( G6PD A− ) individuals ( −2.5 g/dl ; 95 % confidence interval [ 95 % CI ] , −1.2 to −3.8 g/dl ) but was also observed in heterozygotes ( G6PD A ) ( −1.6 g/dl ; 95 % CI , −0.9 to −2.2 g/dl ) and individuals with the wild-type genotype ( G6PD B ) ( −0.5 g/dl ; 95 % CI , −0.4 to −0.6 g/dl ) . Moderate anemia ( Hb level of < 8 g/dl ) was observed in 40 % ( 6/15 individuals ) of the G6PD A− , 11.1 % ( 3/27 individuals ) of the G6PD A , and 4.5 % ( 18/399 individuals ) of the G6PD B individuals ; one case of severe anemia ( Hb level of < 5 g/dl ) was observed . PQ may cause moderate anemia when coadministered with artemisinins , and excluding individuals based on G6PD status alone may not be sufficient to prevent PQ-induced hemolysis ABSTRACT The activities of primaquine in combination with quinine or artesunate against asexual- and sexual-stage parasites were assessed in 176 adult Thai patients with uncomplicated Plasmodium falciparum malaria . Patients were r and omized to one of the six following 7-day oral treatment regimens : ( i ) quinine alone , ( ii ) quinine with tetracycline , ( iii ) quinine with primaquine at 15 mg/day , ( iv ) quinine with primaquine at 30 mg/day , ( v ) artesunate alone , or ( vi ) artesunate with primaquine . Clinical recovery occurred in all patients . There were no significant differences in fever clearance times , rates of P. falciparum reappearance , or recurrent vivax malaria between the six treatment groups . Patients treated with artesunate alone or in combination with primaquine had significantly shorter parasite clearance times ( mean ± st and ard deviation = 65± 18 versus 79 ± 21 h ) and lower gametocyte carriage rates ( 40 versus 62.7 % ) than those treated with quinine ( P ≤ 0.007 ) . Primaquine did not affect the therapeutic response ( P > 0.2 ) . Gametocytemia was detected in 98 patients ( 56 % [ 22 % before treatment and 34 % after treatment ] ) . Artesunate reduced the appearance of gametocytemia ( relative risk [ 95 % confidence interval ] = 0.34 [ 0.17 to 0.70 ] ) , whereas combinations containing primaquine result ed in shorter gametocyte clearance times ( medians of 66 versus 271 h for quinine groups and 73 versus 137 h for artesunate groups ; P≤ 0.038 ) . These results suggest that artesunate predominantly inhibits gametocyte development whereas primaquine accelerates gametocyte clearance in P. falciparum malaria Background Effective mass drug administration ( MDA ) with anti-malarial drugs can clear the human infectious reservoir for malaria and thereby interrupt malaria transmission . The likelihood of success of MDA depends on the intensity and seasonality of malaria transmission , the efficacy of the intervention in rapidly clearing all malaria parasite stages and the degree to which symptomatic and asymptomatic parasite carriers participate in the intervention . The impact of MDA with the gametocytocidal drug combination sulphadoxine-pyrimethamine ( SP ) plus artesunate ( AS ) plus primaquine ( PQ , single dose 0.75 mg/kg ) on malaria transmission was determined in an area of very low and seasonal malaria transmission in northern Tanzania . Methods In a cluster-r and omized trial in four villages in Lower Moshi , Tanzania , eight clusters ( 1,110 individuals ; cluster size 47- 209 ) were r and omized to observed treatment with SP+AS+PQ and eight clusters ( 2,347 individuals , cluster size 55- 737 ) to treatment with placebo over three days . Intervention and control clusters were 1 km apart ; households that were located between clusters were treated as buffer zones where all individuals received SP+AS+PQ but were not selected for the evaluation . Passive case detection was done for the entire cohort and active case detection in 149 children aged 1 - 10 year from the intervention arm and 143 from the control arm . Four cross-sectional surveys assessed parasite carriage by microscopy and molecular methods during a five-month follow-up period . Results The coverage rate in the intervention arm was 93.0 % ( 1,117/1,201 ) . Parasite prevalence by molecular detection methods was 2.2 - 2.7 % prior to the intervention and undetectable during follow-up in both the control and intervention clusters . None of the slides collected during cross-sectional surveys had microscopically detectable parasite densities . Three clinical malaria episodes occurred in the intervention ( n = 1 ) and control clusters ( n = 2 ) . Conclusions This study illustrates the possibility to achieve high coverage with a three-day intervention but also the difficulty in defining suitable outcome measures to evaluate interventions in areas of very low malaria transmission intensity . The decline in transmission intensity prior to the intervention made it impossible to assess the impact of MDA in the chosen study setting .Trial Registration Clinical Trials.gov : Background P. falciparum gametocytes may persist after treatment with sulphadoxine-pyrimethamine ( SP ) plus artesunate ( AS ) and contribute considerably to malaria transmission . We determined the efficacy of SP+AS plus a single dose of primaquine ( PQ , 0.75 mg/kg ) on clearing gametocytaemia measured by molecular methods . Methodology The study was conducted in Mnyuzi , an area of hyperendemic malaria in north-eastern Tanzania . Children aged 3–15 years with uncomplicated P. falciparum malaria with an asexual parasite density between 500–100,000 parasites/µL were r and omized to receive treatment with either SP+AS or SP+AS+PQ . P. falciparum gametocyte prevalence and density during the 42-day follow-up period were determined by real-time nucleic acid sequence-based amplification ( QT-NASBA ) . Haemoglobin levels ( Hb ) were determined to address concerns about haemolysis in G6PD-deficient individuals . Results 108 individuals were r and omized . Pfs25 QT-NASBA gametocyte prevalence was 88–91 % at enrolment and decreased afterwards for both treatment arms . Gametocyte prevalence and density were significantly lower in children treated with SP+AS+PQ . On day 14 after treatment 3.9 % ( 2/51 ) of the SP+AS+PQ treated children harboured gametocytes compared to 62.7 % ( 32/51 ) of those treated with SP+AS ( p<0.001 ) . Hb levels were reduced in the week following treatment with SP+AS+PQ and this reduction was related to G6PD deficiency . The Hb levels of all patients recovered to pre-treatment levels or greater within one month after treatment . Conclusions PQ clears su bmi croscopic gametocytes after treatment with SP+AS and the persisting gametocytes circulated at densities that are unlikely to contribute to malaria transmission . For individuals without severe anaemia , addition of a single dose of PQ to an efficacious antimalarial drug combination is a safe approach to reduce malaria transmission following treatment . Trial Registration Controlled-Trials.com IS RCT Background In areas of seasonal malaria transmission , treatment of asymptomatic carriers of malaria parasites , whose parasitaemia persists at low densities throughout the dry season , could be a useful strategy for malaria control . We carried out a r and omized trial to compare two drug regimens for clearance of parasitaemia in order to identify the optimum regimen for use in mass drug administration in the dry season . Methodology and Principal Findings A two-arm open-label r and omized controlled trial was conducted during the dry season in an area of distinct seasonal malaria in two villages in Gedarif State in eastern Sudan . Participants were asymptomatic adults and children aged over 6 months , with low-density P. falciparum infection detected by PCR . Participants were r and omized to receive artesunate/sulfadoxine-pyrimethamine ( AS+SP ) combination for three days with or without a dose of primaquine ( PQ ) on the fourth day . Parasitaemia detected by PCR on days 3 , 7 and 14 after the start of treatment and gametocytes detected by RT-PCR on days 7 and 14 were then recorded . 104 individuals who had low density parasitaemia at screening were r and omized and treated during the dry season . On day 7 , 8.3 % were positive by PCR in the AS+SP+PQ group and 6.5 % in the AS+SP group ( risk difference 1.8 % , 95%CI −10.3 % to + 13.8 % ) . At enrolment , 12 % ( 12/100 ) were carrying gametocytes . This was reduced to 6.4 % and 4.4 % by day 14 ( Risk Output:	Authors ' conclusions In individual patients , PQ added to malaria treatments reduces gametocyte prevalence when given in doses greater than 0.4 mg/kg . No included trials evaluated whether this policy has an impact on community malaria transmission either in low-endemic setting s approaching elimination , or in highly-endemic setting s where many people are infected but have no symptoms and are unlikely to be treated . For the currently recommended low dose regimen , there is little direct evidence to be confident that the effect of reduction in gametocyte prevalence is preserved . Most trials excluded people with G6PD deficiency , and thus there is little reliable evidence from controlled trials of the safety of PQ in single dose or short course . Overall the safety of PQ given as a single dose was poorly evaluated across all studies , so these data do not demonstrate whether the drug is safe or potentially harmful at this dosing level
MS21926	*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 Sunitinib is an oral tyrosine kinase inhibitor of VEGF , PDGF , c-KIT , and flt-3 receptors . A pediatric phase I study of sunitinib capsules identified the maximum tolerated dose as 15 mg/m2/day . This study was conducted to evaluate sunitinib given as a powder formulation . Methods Sunitinib 15 mg/m2 was administered orally daily for 4 weeks on/2 weeks off to patients < 21 years old with refractory solid tumors . Sunitinib capsules were opened , and the powder sprinkled onto applesauce or yogurt . Plasma levels of sunitinib and an active metabolite , SU12662 , were measured , and pharmacokinetic parameters were estimated . Results 12 patients , median age 13 ( range 4–21 ) years , were treated . The most common first-cycle toxicities were leucopenia ( n = 6 ) , fatigue ( n = 5 ) , neutropenia ( n = 4 ) , and hypertension ( n = 4 ) . Three patients had dose-limiting toxicities ( DLTs ) in cycle 1 ( dizziness/back pain , h and –foot syndrome , and intratumoral hemorrhage/hypoxia ) . A median peak plasma sunitinib concentration of 21 ( range 6–36 ) ng/ml was reached at a median of 4 ( range 4–8 ) h after the first dose . The median exposure ( AUC0–48 ) was 585 ( range 196–1,059 ) h ng/l . The median half-life was 23 ( range 13–36 ) h. The median trough concentration measured before day 14 dosing was 32 ( range 12–58 ) ng/ml . Conclusions The pharmacokinetic profile of sunitinib appears similar between a powder formulation and published data using capsules . The powder formulation allows patients unable to swallow capsules to receive sunitinib ABSTRACT Two multicenter , open-label , single-arm , two-phase studies evaluated single-dose pharmacokinetics and single- and multiple-dose safety of a pediatric oral famciclovir formulation ( prodrug of penciclovir ) in children aged 1 to 12 years with suspicion or evidence of herpes simplex virus ( HSV ) or varicella-zoster virus ( VZV ) infection . Pooled pharmacokinetic data were generated after single doses in 51 participants ( ∼12.5 mg/kg of body weight [ BW ] for children weighing < 40 kg and 500 mg for children weighing ≥40 kg ) . The average systemic exposure to penciclovir was similar ( 6- to 12-year-olds ) or slightly lower ( 1- to < 6-year-olds ) than that in adults receiving a 500-mg dose of famciclovir ( historical data ) . The apparent clearance of penciclovir increased with BW in a nonlinear manner , proportional to BW0.696 . An eight-step weight-based dosing regimen was developed to optimize exposure in smaller children and was used in the 7-day multiple-dose safety phases of both studies , which enrolled 100 patients with confirmed/suspected viral infections . Twenty-six of 47 ( 55.3 % ) HSV-infected patients who received famciclovir twice a day and 24 of 53 ( 45.3 % ) VZV-infected patients who received famciclovir three times a day experienced at least one adverse event . Most adverse events were gastrointestinal in nature . Exploratory analysis following 7-day famciclovir dosing regimen showed resolution of symptoms in most children with active HSV ( 19/21 [ 90.5 % ] ) or VZV disease ( 49/53 [ 92.5 % ] ) . Famciclovir formulation ( sprinkle capsules in OraSweet ) was acceptable to participants /caregivers . In summary , we present a weight-adjusted dosing schedule for children that achieves systemic exposures similar to those for adults given the 500-mg dose Background Efforts to ease administration and enhance acceptability of the oral anti-malarial artemether-lumefantrine ( A-L ) crushed tablet to infants and children triggered the development of a novel dispersible tablet of A-L. During early development of this new formulation , two studies were performed in healthy subjects , one to evaluate the palatability of three flavours of A-L , and a second one to compare the bioavailability of active principles between the dispersible tablet and the tablet ( administered crushed and intact ) . Methods Study 1 was performed in 48 healthy schoolchildren in Tanzania . Within 1 day , all subjects tasted a strawberry- , orange- and cherry-flavoured oral A-L suspension for 10 seconds ( without swallowing ) in a r and omized , single-blind , crossover fashion . The palatability of each formulation was rated using a visual analogue scale ( VAS ) . Study 2 was an open , r and omized crossover trial in 48 healthy adults given single doses of A-L ( 80 mg artemether + 480 mg lumefantrine ) with food . The objectives were to compare the bioavailability of artemether , dihydroartemisinin ( DHA ) and lumefantrine between the dispersible tablet and the tablet administered crushed ( primary objective ) and intact ( secondary objective ) . Results Study 1 showed no statistically significant difference in VAS scores between the three flavours but cherry had the highest score in several ratings ( particularly for overall liking ) . Study 2 demonstrated that the dispersible and crushed tablets delivered bioequivalent artemether , DHA and lumefantrine systemic exposure ( area under the curve [ AUC ] ) ; mean ± SD AUC0-tlast were 208 ± 113 vs 195 ± 93 h.ng/ml for artemether , 206 ± 81 vs 199 ± 84 h.ng/ml for DHA and 262 ± 107 vs 291 ± 106 h.μg/ml for lumefantrine . Bioequivalence was also shown for peak plasma concentrations ( Cmax ) of DHA and lumefantrine . Compared with the intact tablet , the dispersible tablet result ed in bioequivalent lumefantrine exposure , but AUC and Cmax values of artemether and DHA were 20 - 35 % lower . Conclusions Considering that cherry was the preferred flavour , and that the novel A-L dispersible tablet demonstrated similar pharmacokinetic performances to the tablet administered crushed , a cherry-flavoured A-L dispersible tablet formulation was selected for further development and testing in a large efficacy and safety study in African children with malaria The aim of this work was to develop indinavir pediatric anti-HIV/AIDS formulations enabling convenient dose adjustment , ease of oral administration , and improved organoleptic properties by means of the generation of drug-loaded microparticles made of a polymer that is insoluble under intake conditions and dissolves fast in the stomach in order to completely release the active agent . Indinavir-loaded microparticles made of a pH-dependent polymeric excipient soluble at pH < 5 , Eudragit E100 , were prepared using a double emulsion solvent diffusion technique and the in vitro release profiles characterized . Finally , taste masking properties were evaluated in blind r and omized sensory experiments by ten healthy human volunteers . The use of a w/o/o emulsion system result ed in indinavir loads around 90 % . Thermal analysis of the microparticles by differential scanning calorimetry revealed that indinavir appeared mainly dispersed at the molecular level . Concentrations of residual organic solvents as determined by gas chromatography were below the upper limits specified by the European Pharmacopeia for pharmaceutical oral formulations . Then , the behavior of drug-containing microparticles in aqueous media at different pH values was assessed . While they selectively dissolved in gastric-like medium , in tap water ( intake conditions ) , the matrix remained almost unchanged and efficiently prevented drug dissolution . Finally , sensoring taste tests performed by volunteers indicated that systems with indinavir loads ∼15 % displayed acceptable taste . This work explored the production of indinavir-containing microparticles based on a common pharmaceutical excipient as a means for the improvement of medicines of drugs involved in the treatment of HIV/AIDS . For systems containing about 15 % drug , taste studies confirmed the acceptability of the formulation . In pediatric regimes , this composition would require an acceptable amount of formulation ( 0.7–1.5 g ) Verrotti A , Nanni G , Agostinelli S , Tozzi Alleva E , Aloisi P , Franzoni E , Spalice A , Chiarelli F , Coppola G. Effects of the abrupt switch from solution to modified‐release granule formulation of valproate . Acta Neurol Sc and : 2012 : 125 : e14–e18 . © 2011 John Wiley & Sons Abstract Objectives : Traditional Chinese medicine ( TCM ) is popular as an alternative medicine in children with atopic dermatitis ( AD ) . A concoction of five herbs in a capsular preparation has been confirmed to be efficacious in improving the quality of life and sparing topical corticosteroid usage . We evaluated the clinical efficacy and tolerability of the same concoction in syrup form . Methods : This was a prospect i ve self-controlled trial set in the pediatric dermatology clinic of a teaching hospital . Children aged 4–7 years with moderate-to-severe AD received 20 ml of TCM syrup daily . Clinical parameters and laboratory markers were measured before and at 2 weeks , 7 weeks and 12 weeks of treatment , and at 4 weeks after completion . Disease severity was evaluated by the SCORing Atopic Dermatitis ( SCORAD ) index and quality of life by the Children 's Dermatology Life Quality Index ( CDLQI ) . Blood was obtained for a complete blood count , total IgE , eosinophil count , and biochemical studies prior to and after 3 months of TCM usage . Results : Twenty-two patients participated in the study . There were significant improvements in the objective SCORAD , pruritus and CDLQI scores 4 weeks after study completion . There was no change in sleep score or amount of topical steroid consumption . No biochemical evidence of any adverse drug reaction was observed during the study period . The TCM syrup was generally palatable and well tolerated by the children . Adverse effects were generally mild but two patients with rash withdrew during the study . Conclusion : The palatability means that further evaluations and dosage studies of the concoction will be possible in young children BACKGROUND Palatability is an important factor in medication compliance for children where the acceptability of a liquid medication and its ease of administration will be greatly affected by its taste . OBJECTIVES The objective of this study was to determine which , if any of two steroid preparations , oral dexamethasone or oral prednisolone , was more palatable to children requiring steroid treatment for asthma . METHODS A single-blind taste test of 2 different steroid suspensions , liquid prednisolone ( 1mg/ml ) versus liquid dexamethasone ( 1mg/ml ) , was conducted in children aged 5 - 12 years , presenting to the pediatric emergency department with an exacerbation of asthma requiring steroid treatment . Children received 2.5mls of either prednisolone or dexamethasone and were asked to score their impression of taste on a 10 cm visual analog scale . After cleansing of the palate they were given the other steroid and scored its taste . RESULTS Thirty-nine children ( 54 % male ) were enrolled in the study . The mean age was 7.1 years ( SD=2.0 ) . The median visual analog scale measurement for dexamethasone was 8.2 cm ( IQR= 5.2 ) whilst the median measurement for prednisolone was 5.0 cm ( IQR= 7.3 ) , p=0.03 . Male children were more likely to prefer dexamethasone than females with a median score of 9.9 cm ( IQR=3.8 ) for males vs. 5.9 cm ( IQR=9.3 ) for females , p=0.005 . There was no gender preference for prednisolone . CONCLUSIONS There was a statistically significant difference between the taste of dexamethasone and prednisolone , with dexamethasone being the preferred steroid among pediatric patients with asthma . Males were much more likely to prefer dexamethasone than females BACKGROUND Deferasirox is a once-daily , oral iron chelator that was developed out of a need for a long-acting , conveniently-administered chelator for patients with transfusional hemosiderosis . The approved mode of administration requires taking deferasirox on an empty stomach with water , apple juice , or orange juice to limit variation in bioavailability . This required administration schedule might not be palatable for patients . Additionally , approximately one-quarter of patients experience mild to moderate gastrointestinal ( GI ) symptoms , which may pose additional challenges , particularly in the younger and older age ranges . We present a trial to assess the palatability and safety of various administration modes of deferasirox in pediatric and adult patients . PROCEDURES Participants rated palatability in a 4-week run-in phase , where deferasirox was administered per label . Subsequently , patients rated several administration modes during a 3-month assessment phase . RESULTS Palatability was more favorable during the Output:	Limited evidence regarding a correlation between palatability and treatment adherence in pediatric patients was identified
MS21927	*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 : Withdrawal of life-sustaining therapy may lead to premature limitations of life-saving treatments among patients with intracranial hemorrhage , representing a self-fulfilling prophecy . We aim ed to determine whether our algorithm for the withdrawal of life-sustaining therapy decision would accurately identify patients with a high probability of poor outcome , despite aggressive treatment . Design : Retrospective analysis of prospect ively collected data . Setting : Tertiary-care Neuro-ICU . Patients : Intraparenchymal , subdural , and subarachnoid hemorrhage patients . Interventions : Baseline demographics , clinical status , and hospital course were assessed to determine the predictors of in-hospital mortality and 12-month death/severe disability among patients receiving maximal therapy . Multivariable logistic regression models developed on maximal therapy patients were applied to patients who underwent withdrawal of life-sustaining therapy to predict their probable outcome had they continued maximal treatment . A validation cohort of propensity score – matched patients was identified from the maximal therapy cohort , and their predicted and actual outcomes compared . Measurements and Main Results : Of 383 patients enrolled , there were 128 subarachnoid hemorrhage ( 33.4 % ) , 134 subdural hematoma ( 35.0 % ) , and 121 intraparenchymal hemorrhage ( 31.6 % ) . Twenty-six patients ( 6.8 % ) underwent withdrawal of life-sustaining therapy and died , 41 ( 10.7 % ) continued maximal therapy and died in hospital , and 316 ( 82.5 % ) continued maximal therapy and survived to discharge . The median predicted probability of in-hospital death among withdrawal of life-sustaining therapy patients was 35 % had they continued maximal therapy , whereas the median predicted probability of 12-month death/severe disability was 98 % . In the propensity-matched validation cohort , 16 of 20 patients had greater than or equal to 80 % predicted probability of death/severe disability at 12 months , matching the observed outcomes and supporting the strength and validity of our prediction models . Conclusions : The withdrawal of life-sustaining therapy decision may contribute to premature in-hospital death in some patients who may otherwise have been expected to survive to discharge . However , based on probability models , nearly all of the patients who underwent withdrawal of life-sustaining therapy would have died or remained severely disabled at 12 months had maximal therapy been continued . Withdrawal of life-sustaining therapy may not represent a self-fulfilling prophecy Objective : To study the impact of neurologic prognostication on the decision to withdraw life-sustaining therapies ( LST ) in comatose patients resuscitated after cardiac arrest . Methods : The authors prospect ively studied a consecutive series of post-resuscitation comatose patients referred for neurologic prognostication at a single center for 4 years . For most patients , neurologic prognostication was not sought due to early death or rapid return to consciousness . Prognostication was based on Glasgow Coma Score ( GCS ) and Brainstem Reflex Score ( BRS ) , with EEG and cortical evoked potentials ( CEP ) , which were grade d as benign , uncertain , and malignant . The outcomes were as follows : survivors ( Group S ) , brain or cardiac death ( Group D ) , and death from withdrawal of life sustaining therapy ( Group W ) . In Group W , the time interval to withdrawal of LST was analyzed by EEG and CEP grade s. Results : Of 58 patients studied , 10 were in Group S , 8 in Group D , and 40 in Group W. Initial median GCS and BRS was similar for all groups with significant improvement noted in Group S , but not in Group D or Group W. In Group W , CEP grade correlated with the median duration of continued therapy before a decision to withdraw LST : 7 days for benign CEP , 2 days for uncertain CEP , and 1 day for malignant CEP , p = 0.0004 . Conclusion : In patients with poor neurologic recovery early after resuscitation from cardiac arrest , physicians appear to use the cortical evoked potential grade to estimate prognosis . Cortical evoked potential grade correlated with the waiting time until life sustaining therapies were withdrawn after no improvement in neurologic examination was seen Background Prognostication of mortality or severe disability often prompts withdrawal of technological life support in patients following aneurysmal subarachnoid hemorrhage ( aSAH ) . We assessed admission factors impacting decisions to withdraw treatment after aSAH . Methods Prospect ively collected data of aSAH patients admitted to our institution between 1991 and 2009 were review ed . Patients given comfort care measures were identified , including early withdrawal of treatment ( < 72 h after admission ) . Independent predictors of treatment withdrawal were assessed with multivariable analysis . Results The study included 1,134 patients , of whom 72 % were female , 58 % white , and 38 % black or African-American . Mean age was 52.5 ± 14.0 years . In-hospital mortality was 18.3 % . Of the 207 patients who died , treatment was withdrawn in 72 ( 35 % ) and comfort measures instituted early in 31 ( 15 % ) . Among patients who died , WOLST was associated with older age ( 63.6 ± 14.2 years , WOLST vs. 55.6 ± 13.7 years , no WOLST , p < 0.001 ) ; GCS score < 8 ( 62 % of WOLST vs. 44 % with no WOLST , p = 0.010 ) ; HH > 3 ( 72 % of WOLST vs. 53 % with no WOLST , p = 0.008 ) ; and hydrocephalus ( 81 % of WOLST vs. 63 % with no WOLST , p = 0.009 ) . Independent predictors of WOLST were poorer Hunt and Hess grade ( AOR 1.520 , 95 % CI 1.160–1.992 , p = 0.002 ) and older age ( AOR 1.045 , 95 % CI 1.022–1.068 , p < 0.001 ) with the latter also impacting early WOLST decisions . Conclusions Older age and poor clinical grade on presentation predicted WOLST , and age predicted decisions to withdraw treatment earlier following aSAH . While based on prognosis , and in some cases patient wishes , this may also constitute a self-fulfilling prophecy in others Objective : Many intensive care unit ( ICU ) physicians have withdrawn life-support from a patient who lacked decision-making capacity and a surrogate decision-maker , yet little is known about the decision-making practice s for these patients . We sought to determine how often such patients are admitted to the ICU of a metropolitan hospital and how end-of-life decisions are made for them . Design : Prospect i ve , observational cohort study . Patients and Setting : Consecutive adult patients admitted to the medical ICU of a metropolitan West Coast hospital during a 7-month period in 2003 to 2004 . Measurements : Attending physicians completed a question naire about the decision-making process for each patient for whom they considered limiting life-support who lacked decisional capacity and a legally recognized surrogate decision-maker . Main Results : Of the 303 patients admitted during the study period , 49 ( 16 % ; 95 % confidence interval [ CI ] , 12–21 % ) lacked decision-making capacity and a surrogate during the entire ICU stay . Compared with all other ICU patients , these patients were more likely to be male ( 88 % vs. 69 % ; p = .002 ) , white ( 42 % vs. 23 % ; p = .028 ) , and ≥65 yrs old ( 29 % vs. 13 % ; p = .007 ) . Physicians considered withholding or withdrawing treatment from 37 % ( 18 ) of the 49 patients who lacked both decision-making capacity and a surrogate decision-maker . For 56 % ( 10 ) of these 18 patients , the opinion of another attending physician was obtained ; for 33 % ( 6 of 18 ) , the ICU team made the decision independently , and for 11 % ( 2 of 18 ) , the input of the courts or the hospital ethics committee was obtained . Overall , 27 % of deaths ( 13 of 49 ) during the study period were in incapacitated patients who lacked a surrogate ( 95 % CI , 15–41 % ) . Conclusions : Sixteen percent of patients admitted to the medical ICU of this hospital lacked both decision-making capacity and a surrogate decision-maker . Decisions to limit life support were generally made by physicians without judicial or institutional review . Further research and debate are needed to develop optimal decision-making strategies for these difficult cases Withdrawal of care has increased in recent years as the population older than 65 years of age has increased . We sought to investigate the impact of this decision on our mortality rate . We retrospectively review ed a prospect ively collected data base to determine the percentage of cases in which care was actively withdrawn . Neurologic injury as the cause for withdrawal , age of the patient , number of days to death , number of cases thought to be treatment failures , and the reason for failure were analyzed . Between January 2008 and December 2012 , there were 536 trauma service deaths ; 158 ( 29.5 % ) had care withdrawn . These patients were 67 ( 6 18.5 ) years old and neurologic injury was responsible in 63 per cent ( 6 5.29 % ) . Fifty-two per cent of the patients died by Day 3 ; 65 per cent by Day 5 ; and 74 per cent Day 7 . A total of 22.7 per cent ( 6 7.9 % ) could be considered a treatment failure . Accounting for cases in which care was withdrawn for futility would decrease the overall mortality rate by approximately 23 per cent . Trauma center mortality calculation does not account for care withdrawn . Treating an active , aging population , with advance directives , requires method ologies that account for such decision-making when determining mortality rates Objectives : To characterize the prevalence of withdrawal of life-sustaining treatment , as well as the time to awakening , short-term neurologic outcomes , and cause of death in comatose survivors of out-of-hospital resuscitated cardiopulmonary arrests treated with therapeutic hypothermia . Design : Single center , prospect i ve observational cohort study of consecutive patients with out-of-hospital cardiopulmonary arrests . Setting : Academic tertiary care hospital and level one trauma center in Minneapolis , MN . Patients : Adults with witnessed , nontraumatic , out-of-hospital cardiopulmonary arrests regardless of initial electrocardiographic rhythm with return of spontaneous circulation who were admitted to an ICU . Interventions : None . Measurements and Main Results : The study cohort included 154 comatose survivors of witnessed out-of-hospital cardiopulmonary arrests who were admitted to an ICU during the 54-month study period . One hundred eighteen patients ( 77 % ) were treated with therapeutic hypothermia . The mean age was 59 years , 104 ( 68 % ) were men , and 83 ( 54 % ) had an initial rhythm of ventricular tachycardia or fibrillation . Only eight of all 78 patients ( 10 % ) who died qualified as brain dead ; and 81 % of all patients ( 63 of 78 ) who died did so after withdrawal of life-sustaining treatment . Twenty of 56 comatose survivors ( 32 % ) treated with hypothermia who awoke ( as defined by Glasgow Motor Score of 6 ) and had good neurologic outcomes ( defined as Cerebral Performance Category 1–2 ) did so after 72 hours . Conclusions : Our study supports delaying prognostication and withdrawal of life-sustaining treatment to beyond 72 hours in cases treated with therapeutic hypothermia . Larger multicenter prospect i ve studies are needed to better define the most appropriate time frame for prognostication in comatose cardiac arrest survivors treated with therapeutic hypothermia . These data are also consistent with the notion that a majority of out-of-hospital cardiopulmonary arrest survivors die after a decision to withdrawal of life-sustaining treatment and that very few of these survivors progress to brain death In some intensive care units ( ICUs ) , fewer patients who die now undergo attempts at cardiopulmonary resuscitation ( CPR ) , and many more have life support actively withdrawn prior to death than did a decade ago . To determine the frequency of withdrawal of life support , we contacted every American postgraduate training program with significant clinical exposure to critical care medicine , asking them prospect ively to classify patients who died into one of five mutually exclusive categories . We received data from 131 ICUs at 110 institutions in 38 states . There were 6,303 deaths , of which 393 patients were brain dead . Of the remaining 5,910 patients who died , 1,544 ( 23 % ) received full ICU care including failed cardiopulmonary resuscitation ( CPR ) ; 1,430 ( 22 % ) received full ICU care without CPR ; 797 ( 10 % ) had life support withheld ; and 2,139 ( 38 % ) had life support withdrawn . There was wide variation in practice among ICUs , with ranges of 4 to 79 % , 0 to 83 % , 0 to 67 % , and 0 to 79 % in these four categories , respectively . Variation was not Output:	Based on several large , multicenter studies , there was a trend toward a higher frequency of limitation of LST over time . However , there is large variability between ICUs in the proportion of patients with limitations and on the proportion of deaths preceded by a limitation . Increases in the frequency of limitations of LST over time suggests changing attitudes about aggressive end-of-life-care . Limitations are more common for patients with worse premorbid health and greater ICU illness severity . While some differences in the frequency of limitations of LST may be explained by personal factors such as race , there is unexplained wide variability between units
MS21928	*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 Malaria continues to be a prominent global public health challenge . This study tested the effectiveness of two service delivery models for reducing the malaria burden , e.g. supportive supervision of community health workers ( CHW ) and community mobilization in promoting appropriate health-seeking behaviour for febrile illnesses in Odisha , India . Methods The study population comprised 120 villages from two purposively chosen malaria-endemic districts , with 40 villages r and omly assigned to each of the two treatment arms , one with both supportive supervision and community mobilization and one with community mobilization alone , as well as an observational control arm . Outcome measures included changes in the utilization of bed nets and timely care-seeking for fever from a trained provider compared to the control group . Analysis was by intention-to-treat . Results Significant improvements were observed in the reported utilization of bed nets in both intervention arms ( 84.5 % in arm A and 82.4 % in arm B versus 78.6 % in the control arm ; p < 0.001 ) . While overall rates of treatment-seeking were equal across study arms , treatment-seeking from a CHW was higher in both intervention arms ( 28 % ; p = 0.005 and 27.6 % ; p = 0.007 ) than in the control arm ( 19.2 % ) . Fever cases were significantly more likely to visit a CHW and receive a timely diagnosis of fever in the combined interventions arm than in the control arm ( 82.1 % vs. 67.1 % ; p = 0.025 ) . Care-seeking from trained providers also increased with a substitution away from untrained providers . Further , fever cases from the combined interventions arm ( 60.6 % ; p = 0.004 ) and the community mobilization arm ( 59.3 % ; p = 0.012 ) were more likely to have received treatment from a skilled provider within 24 hours than fever cases from the control arm ( 50.1 % ) . In particular , women from the combined interventions arm were more likely to have received timely treatment from a skilled provider ( 61.6 % vs. 47.2 % ; p = 0.028 ) . Conclusion A community-based intervention combining the supportive supervision of community health workers with intensive community mobilization and can be effective in improving care-seeking and preventive behaviour and may be used to strengthen the national malaria control programme Background Intermittent preventive treatment of malaria in children ( IPTc ) involves the administration of a course of anti-malarial drugs at specified time intervals to children at risk of malaria regardless of whether or not they are known to be infected . IPTc provides a high level of protection against uncomplicated and severe malaria , with monthly sulphadoxine-pyrimethamine plus amodiaquine ( SP&AQ ) and sulphadoxine-pyrimethamine plus piperaquine being the most efficacious regimens . A key challenge is the identification of a cost-effective delivery strategy . Methods A community r and omized trial was undertaken in Jasikan district , Ghana to assess IPTc effectiveness and costs using SP&AQ delivered in three different ways . Twelve villages were r and omly selected to receive IPTc from village health workers ( VHWs ) or facility-based nurses working at health centres ' outpatient departments ( OPD ) or EPI outreach clinics . Children aged 3 to 59 months-old received one IPT course ( three doses ) in May , June , September and October . Effectiveness was measured in terms of children covered and adherent to a course and delivery costs were calculated in financial and economic terms using an ingredient approach from the provider perspective . Results The economic cost per child receiving at least the first dose of all 4 courses was US$ 4.58 when IPTc was delivered by VHWs , US$ 4.93 by OPD nurses and US$ 5.65 by EPI nurses . The unit economic cost of receiving all 3 doses of all 4 courses was US$ 7.56 and US$ 8.51 when IPTc was delivered by VHWs or facility-based nurses respectively . The main cost driver for the VHW delivery was supervision , reflecting re sources used for travelling to more remote communities rather than more intense supervision , and for OPD and EPI delivery , it was the opportunity cost of the time spent by nurses in dispensing IPTc . Conclusions VHWs achieve higher IPTc coverage and adherence at lower costs than facility-based nurses in Jasikan district , Ghana . Trial Registration Clinical Trials.gov NCT00119132 Background Intermittent preventive treatment for malaria in children ( IPTc ) is a promising new intervention for the prevention of malaria but its delivery is a challenge . We have evaluated the coverage of IPTc that can be achieved by two different delivery systems in Ghana . Methods IPTc was delivered by volunteers in six villages ( community-based arm ) and by health workers at health centres or at Exp and ed Programme on Immunisation outreach clinics ( facility based ) in another six communities . The villages were selected r and omly and drugs were administered in May , June , September and October 2006 . The first dose of a three-dose regimen of amodiaquine plus sulphadoxine-pyrimethamine was administered under supervision to 3–59 month-old children ( n = 964 ) in the 12 study villages ; doses for days 2 and 3 were given to parents/guardians to administer at home . Results The proportion of children who received at least the first dose of 3 or more courses of IPTc was slightly higher in the community based arm ( 90.5 % vs 86.6 % ; p = 0.059 ) . Completion of the three dose regimen was high and similar with both delivery systems ( 91.6 % and 91.7 % respectively ) . Conclusion Seasonal IPTc delivered through community-based or facility-based systems can achieve a high coverage rate with the support and supervision of the district health management team . However , in order to maximise the impact of IPTc , both delivery systems may be needed in some setting s. Trial Registration Clinical Trials.gov 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 BACKGROUND No satisfactory strategy for reducing high child mortality from malaria has yet been established in tropical Africa . We compared the effect on under-5 mortality of teaching mothers to promptly provide antimalarials to their sick children at home , with the present community health worker approach . METHODS Of 37 tabias ( cluster of villages ) in two districts with hyperendemic to holoendemic malaria , tabias reported to have the highest malaria morbidity were selected . A census was done which included a maternity history to determine under-5 mortality . Tabias ( population 70,506 ) were paired according to under-5 mortality rates . One tabia from each pair was allocated by r and om number to an intervention group and the other was allocated to the control group . In the intervention tabias , mother coordinators were trained to teach other local mothers to recognise symptoms of malaria in their children and to promptly give chloroquine . In both intervention and control tabias , all births and deaths of under-5s were recorded monthly . FINDINGS From January to December 1997 , 190 of 6383 ( 29.8 per 1000 ) children under-5 died in the intervention tabias compared with 366 of 7294 ( 50.2 per 1000 ) in the control tabias . Under-5 mortality was reduced by 40 % in the intervention localities ( 95 % CI from 29.2 - 50.6 ; paired t test , p<0.003 ) . For every third child who died , a structured verbal autopsy was undertaken to ascribe cause of mortality as consistent with malaria or possible malaria , or not consistent with malaria . Of the 190 verbal autopsies , 13 ( 19 % ) of 70 in the intervention tabias were consistent with possible malaria compared with 68 ( 57 % ) of 120 in the control tabias . INTERPRETATION A major reduction in under-5 mortality can be achieved in holoendemic malaria areas through training local mother coordinators to teach mothers to give under-5 children antimalarial drugs Background Over thirty years have passed since the Alma-Ata Declaration on primary health care in 1978 . Many governments in the first decade following the declaration responded by developing national programmes of community health workers ( CHWs ) , but evaluations of these often demonstrated poor outcomes . As many CHW programmes have responded to the HIV/AIDS p and emic , international interest in them has returned and their role in the response to other diseases should be examined carefully so that lessons can be applied to their new roles . Over half of the deaths in African children under five years of age are due to malaria , diarrhoea and pneumonia - a situation which could be addressed through the use of cheap and effective interventions delivered by CHWs . However , to date there is very little evidence from r and omised controlled trials of the impacts of CHW programmes on child mortality in Africa . Evidence from non-r and omised controlled studies has not previously been review ed systematic ally . Methods We search ed data bases of published and unpublished studies for RCTs and non-r and omised studies evaluating CHW programmes delivering curative treatments , with or without preventive components , for malaria , diarrhoea or pneumonia , in children in sub-Saharan Africa from 1987 to 2007 . The impact of these programmes on morbidity or mortality in children under six years of age was review ed . A descriptive analysis of interventional and context ual factors associated with these impacts was attempted . Results The review identified seven studies evaluating CHWs , delivering a range of interventions . Limited descriptive data on programmes , context s or process outcomes for these CHW programmes were available . CHWs in national programmes achieved large mortality reductions of 63 % and 36 % respectively , when insecticide-treated nets and anti-malarial chemoprophylaxis were delivered , in addition to curative interventions . Conclusions CHW programmes could potentially achieve large gains in child survival in sub-Saharan Africa if these programmes were implemented at scale . Large-scale rigorous studies , including RCTs , are urgently needed to provide policymakers with more evidence on the effects of CHWs delivering these interventions Background In the rural areas of sub-Saharan Africa , the majority of young children affected by malaria have no access to formal health services . Home treatment through mothers of febrile children supported by mother groups and local health workers has the potential to reduce malaria morbidity and mortality . Methods A cluster-r and omized controlled effectiveness trial was implemented from 2002–2004 in a malaria endemic area of rural Burkina Faso . Six and seven villages were r and omly assigned to the intervention and control arms respectively . Febrile children from intervention villages were treated with chloroquine ( CQ ) by their mothers , supported by local women group leaders . CQ was regularly supplied through a revolving fund from local health centres . The trial was evaluated through two cross-sectional surveys at baseline and after two years of intervention . The primary endpoint of the study was the proportion of moderate to severe anaemia in children aged 6–59 months . For assessment of the development of drug efficacy over time , an in vivo CQ efficacy study was nested into the trial . The study is registered under http://www.controlled-trials.com ( IS RCT N 34104704 ) . Results The intervention was shown to be feasible under program conditions and a total of 1.076 children and 999 children were evaluated at baseline and follow-up time points respectively . Self-reported CQ treatment of fever episodes at home as well as referrals to health centres increased over the study period . At follow-up , CQ was detected in the blood of high proportions of intervention and control children . Compared to baseline findings , the prevalence of anaemia ( 29 % vs 16 % , p < 0.0001 ) and malaria parameters such as prevalence of P. falciparum parasitaemia , fever and palpable spleens was lower at follow-up but there were no differences between the intervention and control group . CQ efficacy decreased over the study period but this was not associated with the intervention . Discussion The decreasing prevalence of malaria morbidity including anaemia over the study period can be explained by an overall increase of malaria prevention and treatment activities in the study area . The lack of effectiveness of the intervention was likely caused by contamination , pre-existing differences in the coverage of malaria treatment in both study groups and an unexpectedly rapid increase of resistance against CQ , the first-line treatment drug at the time of the study Insecticide treatment of bed nets ( " mosquito nets " ) may be a cheap and acceptable method of reducing the morbidity and mortality caused by malaria . In a rural area of The Gambia , bed nets in villages participating in a primary health-care ( PHC ) scheme were treated with permethrin at the beginning of the malaria transmission season . Additionally , children aged 6 months to 5 years were r and omised to receive weekly either chemoprophylaxis with maloprim or a placebo throughout the malaria transmission season . We measured mortality in children in PHC villages before and after the interventions described , and compared this with mortality in villages where no interventions occurred ( non-PHC villages ) . About 92 % of children in PHC villages slept under insecticide-treated bed nets . In the year before intervention , mortality in children aged 1 - 4 years was lower in non-PHC villages . After intervention , the overall mortality and mortality attributable to malaria of children aged 1 - 4 in the intervention villages was 37 % and 30 % , respectively , of that in the non-PHC villages . Among children who Output:	However , the considerable heterogeneity was found in the impact of community-delivered models in reducing , parasitaemia and hyperparasitaemia prevalence , anaemia incidence , fever prevalence and malaria caseload . Conclusion Overall , the community-delivered model is effective in improving the coverage of malaria interventions and reducing malaria-associated mortality .
MS21929	*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 effect of hypoxia on the response to interval exercise was determined in eight elite female cyclists during two interval sessions : a sustained 3 x 10-min endurance set ( 5-min recovery ) and a repeat sprint session comprising three sets of 6 x 15-s sprints ( work-to-relief ratios were 1:3 , 1:2 , and 1:1 for the 1st , 2nd , and 3rd sets , respectively , with 3 min between each set ) . During exercise , cyclists selected their maximum power output and breathed either atmospheric air ( normoxia , 20.93 % O(2 ) ) or a hypoxic gas mix ( hypoxia , 17.42 % O(2 ) ) . Power output was lower in hypoxia vs. normoxia throughout the endurance set ( 244+/-18 vs. 226+/-17 , 234+/-18 vs. 221+/-25 , and 235+/-18 vs. 221+/-25 W for 1st , 2nd , and 3rd sets , respectively ; P < 0.05 ) but was lower only in the latter stages of the second and third sets of the sprints ( 452+/-56 vs. 429+/-49 and 403+/-54 vs. 373+/- 43 W , respectively ; P<0.05 ) . Hypoxia lowered blood O(2 ) saturation during the endurance set ( 92.9+/-2.9 vs. 95.4+/-1.5 % ; P<0.05 ) but not during repeat sprints . We conclude that , when elite cyclists select their maximum exercise intensity , both sustained ( 10 min ) and short-term ( 15 s ) power are impaired during hypoxia , which simulated moderate ( approximately 2,100 m ) altitude PURPOSE Lower barometric air pressure at altitude can affect competitive performance of athletes in some sports . Reported here are the effects of various altitudes on elite track- and -field athletes ' performance . METHODS Lifetime track- and -field performances of athletes placed in the top 16 in at least 1 major international competition between 2000 and 2009 were downloaded from the data base at tilastopaja.org . There were 132,104 performances of 1889 athletes at 794 venues . Performances were log-transformed and analyzed using a mixed linear model with fixed effects for 6 levels of altitude and r and om quadratic effects to adjust for athlete age . RESULTS Men 's and women 's sprint events ( 100 - 400 m ) showed marginal improvements of ~0.2 % at altitudes of 500 - 999 m , and above 1500 m all but the 100- and 110-m hurdles showed substantial improvements of 0.3 - 0.7 % . Some middle- and long-distance events ( 800 - 10,000 m ) showed marginal impairments at altitudes above 150 m , but above 1000 m the impairments increased dramatically to ~2 - 4 % for events > 800 m. There was no consistent trend in the effects of altitude on field events up to 1000 m ; above 1000 m , hammer throw showed a marginal improvement of ~1 % and discus was impaired by 1 - 2 % . Above 1500 m , triple jump and long jump showed marginal improvements of ~1 % . CONCLUSIONS In middle- and long-distance runners , altitudes as low as 150 to 299 m can impair performance . Higher altitudes ( ≥1000 m ) are generally required before decreases in discus performance or enhancements in sprinting , triple and long jump , or hammer throw are seen Purpose To investigate the interaction between the development of peripheral locomotor muscle fatigue , muscle recruitment and performance during repeated-sprint exercise ( RSE ) . Method In a single-blind , r and omised and cross-over design , ten male team-sport athletes performed two RSE ( fifteen 5-s cycling sprints interspersed with 25 s of rest ; power self-selected ) in normoxia and in acute moderate hypoxia ( FIO2 0.138 ) . Mechanical work , total electromyographic intensity ( summed quadriceps electromyograms , RMSsum ) and muscle ( vastus lateralis ) and pre-fontal cortex near-infrared spectroscopy ( NIRS ) parameters were calculated for every sprint . Blood lactate concentration ( [ Lac- ] ) was measured throughout the protocol . Peripheral quadriceps fatigue was assessed via changes in potentiated quadriceps twitch force ( ΔQtw , pot ) pre- versus post-exercise in response to supra-maximal magnetic femoral nerve stimulation . The central activation ratio ( QCAR ) was used to quantify completeness of quadriceps activation . Results Compared with normoxia , hypoxia reduced arterial oxygen saturation ( -13.7 % , P=0.001 ) , quadriceps RMSsum ( -13.7 % , P=0.022 ) , QCAR ( -3.3 % , P=0.041 ) and total mechanical work ( -8.3 % , P=0.019 ) . However , the magnitude of quadriceps fatigue induced by RSE was similar in the two conditions ( ΔQtw , pot : -53.5 % and -55.1 % , P=0.71 ) . The lower cycling performance in hypoxia occurred despite similar metabolic ( muscle NIRS parameters and blood [ Lac- ] ) and functional ( twitch and M-wave ) muscle states . Conclusion Results suggest that the central nervous system regulates quadriceps muscle recruitment and , thereby , performance to limit the development of muscle fatigue during intermittent , short sprints . This finding highlights the complex interaction between muscular perturbations and neural adjustments during sprint exercise , and further supports the presence of pacing during intermittent sprint exercise PURPOSE To underst and the role of O2 utilization in the sex differences of fatigue during intermittent activity , we compared the cerebral ( prefrontal lobe ) and muscle ( vastus lateralis ) oxygenation of men and women during repeated-sprint exercise ( RSE ) . METHODS Ten men and 10 women matched for initial-sprint mechanical work performed ten , 10 s cycle sprints ( with 30 s of rest ) under normoxic ( NM : 21 % FIO2 ) and acute hypoxic ( HY : 13 % FIO2 ) conditions in a r and omized single-blind and crossover design . Mechanical work was calculated and arterial O2 saturation ( SpO2 ) was estimated via pulse oximetry during every sprint . Cerebral and muscle oxy- ( O2Hb ) and deoxy-hemoglobin ( HHb ) were monitored continuously by near-infrared spectroscopy . RESULTS Compared with NM , work decrement was accentuated ( P = 0.01 ) in HY for both men ( -16.4 ± 10.3 % ) and women ( -16.8 ± 9.0 % ) . This was associated with lower SpO2 and lower cerebral Δ[O2Hb ] in both sexes ( -13.6 ± 7.5 % , P = .008 , and -134.5 ± 73.8 % , P = .003 , respectively ) . These HY-induced changes were nearly identical in these men and women matched for initial-sprint work . Muscle Δ[HHb ] increased 9-fold ( P = .009 ) and 5-fold ( P = .02 ) in men and women , respectively , and plateaued . This muscle deoxygenation was not exacerbated in HY . CONCLUSIONS Results indicate that men and women matched for initial-sprint work experience similar levels of fatigue and systemic , cerebral , and peripheral adjustments during RSE performed in NM and HY . These data suggest that cerebral deoxygenation imposes a limitation to repeated-sprint performance The study examined the influence of cerebral ( prefrontal cortex ) and muscle ( vastus lateralis ) oxygenation on the ability to perform repeated , cycling sprints . Thirteen team-sport athletes performed ten , 10-s sprints ( with 30 s of rest ) under normoxic ( FIO2 0.21 ) and acute hypoxic ( FIO2 0.13 ) conditions in a r and omised , single-blind fashion and crossover design . Mechanical work was calculated and arterial O2 saturation ( SpO2 ) was estimated via pulse oximetry for every sprint . Cerebral and muscle oxy-(O2Hb ) , deoxy-(HHb ) , and total haemoglobin ( THb ) were monitored continuously by near-infrared spectroscopy . Compared with normoxia , hypoxia induced larger decrements in SpO2 and work ( 11.6 and 7.6 % , respectively ; P < 0.05 ) . In the muscle , we observed a fairly constant level of deoxygenation across sprints , with no effect of the condition . In normoxia , regional cerebral oxygenation increased during the first two sprints and slightly fluctuated thereafter . In contrast , this initial cerebral hyper-oxygenation was attenuated in hypoxia . Changes in [ O2Hb ] and [ HHb ] occurred earlier and were larger in hypoxia compared with normoxia ( P < 0.05 ) , while regional blood volume ( Δ[THb ] ) remained unaffected by the condition . Changes in cerebral [ HHb ] and mechanical work were strongly correlated in normoxia and hypoxia ( R2 = 0.81 and R2 = 0.85 , respectively ; P < 0.05 ) , although the slope of this relationship differed ( normoxia , −351.3 ± 183.3 vs. hypoxia , −442.4 ± 227.2 ; P < 0.05 ) . The results of this NIRS study show that O2 availability influences prefrontal cortex , but not muscle , oxygenation during repeated , short sprints . By using a hypoxia paradigm , the study suggests that cerebral oxygenation contributes to the impairment of repeated-sprint ability Athletes regularly compete at 2,000–3,000 m altitude where peak oxygen consumption $ $ ( \dot{V}\hbox{\rm O}_{2{\rm peak}})$$ declines ∼10–20 % . Factors other than $ $ \dot{V}\hbox{\rm O}_{2{\rm peak}}$$ including gross efficiency ( GE ) , power output , and pacing are all important for cycling performance . It is therefore imperative to underst and how all these factors and not just $ $ \dot{V}\hbox{\rm O}_{2{\rm peak}}$$ are affected by acute hypobaric hypoxia to select athletes who can compete successfully at these altitudes . Ten well-trained , non-altitude-acclimatised male cyclists and triathletes completed cycling tests at four simulated altitudes ( 200 , 1,200 , 2,200 , 3,200 m ) in a r and omised , counter-balanced order . The exercise protocol comprised 5 × 5-min submaximal efforts ( 50 , 100 , 150 , 200 and 250 W ) to determine submaximal $ $ \dot{V}\hbox{\rm O}_{2}$$ and GE and , after 10-min rest , a 5-min maximal time-trial ( 5-minTT ) to determine $ $ \dot{V}\hbox{\rm O}_{2{\rm peak}}$$ and mean power output ( 5-minTTpower ) . $ $ \dot{V}\hbox{\rm O}_{2{\rm peak}}$$ declined 8.2 ± 2.0 , 13.9 ± 2.9 and 22.5 ± 3.8 % at 1,200 , 2,200 and 3,200 m compared with 200 m , respectively , P < 0.05 . The corresponding decreases in 5-minTTpower were 5.8 ± 2.9 , 10.3 ± 4.3 and 19.8 ± 3.5 % ( P < 0.05 ) . GE during the 5-minTT was not different across the four altitudes . There was no change in submaximal $ $ \dot{V}\hbox{\rm O}_{2}$$ at any of the simulated altitudes , however , submaximal efficiency decreased at 3,200 m compared with both 200 and 1,200 m. Despite substantially reduced power at simulated altitude , there was no difference in pacing at the four altitudes for athletes whose first trial was at 200 or 1,200 m ; whereas athletes whose first trial was at 2,200 or 3,200 m tended to mis-pace that effort . In conclusion , during the 5-minTT there was a dose – response effect of hypoxia on both $ $ \dot{V}\hbox{\rm O}_{2{\rm peak}}$$ and 5-minTTpower but no effect on GE The present study examined the effect of oxygen fraction in inspired air ( FIO2 ) on exercise performance and maximum oxygen consumption ( VO2max ) . Six national level male rowers exercised three 2500-m all-out tests on a Concept II rowing ergometer . Each subject performed one test in normoxia ( FIO2 20.9 % ) , one in simulated hyperoxia ( FIO2 62.2 % ) and one in simulated hypoxia ( FIO2 15.8 % ) in a r and om Output:	TT ( −16.2 ± 4.3 % ; 95 % CI −22.9 % to −9 % ) and TTE ( −44.5 ± 6.9 % ; 95 % CI −51.3 % to −36.7 % ) elicited a negative effect , whilst indicating a quadratic relationship between hypoxic magnitude and both TTE and TT performance . Furthermore , exercise less than 2 min exhibited no ergolytic effect from acute hypoxia . Summary / Conclusion : This review highlights the ergolytic effect of acute hypoxic exposure , which is curvilinear for TTE and TT performance with increasing hypoxic levels , but short duration intermittent and sprint exercise seem to be unaffected
MS21930	*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 Salmon , JR , Roper , JA , and Tillman , MD . Does acute whole-body vibration training improve the physical performance of people with knee osteoarthritis ? J Strength Cond Res 26(11 ) : 2983–2989 , 2012—The purpose of this study was to determine the effects of a single session of whole-body vibration training ( WBVT ) on the physical performance of individuals with knee osteoarthritis ( OA ) in 3 tests design ed to simulate activities of daily living ( ADLs ) . Fifteen individuals with symptomatic knee OA completed the Timed-Up- and -Go Test , step test , 20-m walk test , and visual analog scale ( VAS ) recordings of knee pain intensity . A main effect was detected for time to complete the step test ( F[2,28 ] = 6.243 , p = 0.006 , ) . Post hoc analyses revealed that the time to complete the step test at 5 minutes after WBVT improved significantly ( p = 0.042 ) from that of the pretest . A moderate correlation ( r = 0.465 , p = 0.001 ) was found between the VAS scores and the time to complete the step test across all trials . A main effect was found for time to complete the walk test ( F[2,28 ] = 4.370 , p = 0.022 , ) . Post hoc analyses did not indicate significant improvements from pretest seen at 5 minutes after WBVT ( p = 0.110 ) and 1 hour after WBVT ( p = 0.224 ) . The WBVT was well tolerated in nearly all the participants , and we observed that an acute bout of WBVT was effective in improving the ability of individuals with knee OA to perform a step test and 20-m walk test . Our findings suggest that WBVT may be an effective nonpharmacologic modality to treat some knee OA symptoms and improve ADLs Objective To investigate the effect on pain reduction and strengthening of the whole body vibration ( WBV ) in chronic knee osteoarthritis ( OA ) . Methods Patients were r and omly divided into two groups : the study group ( WBV with home based exercise ) and control group ( home based exercise only ) . They performed exercise and training for 8 weeks . Eleven patients in each group completed the study . Pain intensity was measured with the Numeric Rating Scale ( NRS ) , functional scales were measured with Korean Western Ontario McMaster score ( KWOMAC ) and Lysholm Scoring Scale ( LSS ) , quadriceps strength was measured with isokinetic torque and isometric torque and dynamic balance was measured with the Biodex Stability System . These measurements were performed before training , at 1 month after training and at 2 months after training . Results NRS was significantly decreased in each group , and change of pain intensity was significantly larger in the study group than in the control group after treatment . Functional improvements in KWOMAC and LSS were found in both groups , but no significant differences between the groups after treatment . Dynamic balance , isokinetic strength of right quadriceps and isometric strengths of both quadriceps muscles improved in both groups , but no significant differences between the groups after treatment . Isokinetic strength of left quadriceps did not improve in both groups after treatment . Conclusion In chronic knee OA patients , WBV reduced pain intensity and increased strength of the right quadriceps and dynamic balance performance . In comparison with the home based exercise program , WBV was superior only in pain reduction and similarly effective in strengthening of the quadriceps muscle and balance improvement The aim of this study was to investigate the effect of adding whole-body vibration ( WBV ; frequency = 35 to 40 Hz ; amplitude = 4 mm ) to squat training on the T-cell proliferative response of elderly patients with osteoarthritis ( OA ) of the knee . This study was a r and omized controlled trial in which the selected variables were assessed before and after 12 weeks of training . Twenty-six subjects ( 72 ± 5 years of age ) were divided into three groups : 1 ) squat training with WBV ( WBV , N = 8) ; 2 ) squat training without WBV ( N = 10 ) , and 3 ) a control group ( N = 8) . Women who were ≥60 years of age and had been diagnosed with OA in at least one knee were eligible . The intervention consisted of 12 uninterrupted weeks of squatting exercise training performed 3 times/week . Peripheral blood mononuclear cells were obtained from peripheral blood collected before and after training . The proliferation of TCD4 + and TCD8 + cells was evaluated by flow cytometry measuring the carboxyfluorescein succinimidyl ester fluorescence decay before and after the intervention ( Δ ) . The proliferative response of TCD4 + cells ( P = 0.02 , effect size = 1.0 ) showed a significant decrease ( 23 % ) in the WBV group compared to the control group , while there was no difference between groups regarding the proliferative response of TCD8 + cells ( P = 0.12 , effect size = 2.23 ) . The data suggest that the addition of WBV to squat exercise training might modulate T-cell-mediated immunity , minimizing or slowing disease progression in elderly patients with OA of the knee Background Osteoarthritis ( OA ) is the most common degenerative arthropathy . Load-bearing joints such as knee and hip are more often affected than spine or h and s. The prevalence of gonarthrosis is generally higher than that of coxarthrosis . Because no cure for OA exists , the main emphasis of therapy is analgesic treatment through either mobility or medication . Non-pharmacologic treatment is the first step , followed by the addition of analgesic medication , and ultimately by surgery . The goal of non-pharmacologic and non-invasive therapy is to improve neuromuscular function , which in turn both prevents formation of and delays progression of OA . A modification of conventional physiotherapy , whole body vibration has been successfully employed for several years . Since its introduction , this therapy is in wide use at our facility not only for gonarthrosis , but also coxarthrosis and other diseases leading to muscular imbalance . Methods / Design This study is a r and omized , therapy-controlled trial in a primary care setting at a university hospital . Patients presenting to our outpatient clinic with initial symptoms of gonarthrosis will be assessed against inclusion and exclusion criteria . After patient consent , 6 weeks of treatment will ensue . During the six weeks of treatment , patients will receive one of two treatments , conventional physiotherapy or whole-body-vibration exercises of one hour three times a week . Follow-up examinations will be performed immediately after treatment and after another 6 and 20 weeks , for a total study duration of 6 months . 20 patients will be included in each therapy group . Outcome measurements will include objective analysis of motion and ambulation as well as examinations of balance and isokinetic force . The Western Ontario and McMaster Universities Arthritis Index and SF-12 scores , the patients ' overall status , and clinical examinations of the affected joint will be carried out . Discussion As new physiotherapy techniques develop for the treatment of OA , it is important to investigate the effectiveness of competing strategies . With this study , not only patient-based scores , but also objective assessment s will be used to quantify patient-derived benefits of therapy . Trial registration Deutsches Register Klinischer Studien ( DRKS ) DRKS00000415 Clinical trials.gov NCT01037972EudraCT 2009 - 017617 - In this study , we investigated a new method of training for maximal strength and flexibility , which included exertion with superimposed vibration ( vibratory stimulation , VS ) on target muscles . Twenty-eight male athletes were divided into three groups , and trained three times a week for 3 weeks in one of the following conditions : ( A ) conventional exercises for strength of the arms and VS stretching exercises for the legs ; ( B ) VS strength exercises for the arms and conventional stretching exercises for the legs ; ( C ) irrelevant training ( control group ) . The vibration was applied at 44 Hz while its amplitude was 3 mm . The effect of training was evaluated by means of isotonic maximal force , heel-to-heel length in the two-leg split across , and flex- and -reach test for body flexion . The VS strength training yielded an average increase in isotonic maximal strength of 49.8 % , compared with an average gain of 16 % with conventional training , while no gain was observed for the control group . The VS flexibility training result ed in an average gain in the legs split of 14.5 cm compared with 4.1 cm for the conventional training and 2 cm for the control groups , respectively . The ANOVA revealed significant pre-post training effects and an interaction between pre-post training and ' treatment ' effects ( P < 0.001 ) for the isotonic maximal force and both flexibility tests . It was concluded that superimposed vibrations applied for short periods allow for increased gains in maximal strength and flexibility BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . OBJECTIVES The study objectives were to evaluate the effects of adding whole-body vibration to squat training on functional performance and self-report of disease in elderly individuals with knee osteoarthritis ( OA ) . DESIGN This was a prospect i ve , r and omized trial in which selected variables were evaluated at three periods : 3 weeks prior to the training , immediately prior , and after the end of the training . SUBJECTS Twenty-three ( 23 ) elderly subjects were evaluated using four functional performance tests : Berg Balance Scale ( BBS ) , Timed Get Up and Go Test ( TGUG ) , Chair St and Test ( CST ) , and 6-Minute Walk Test ( 6MWT ) , and a self-report of the status of disease ( WOMAC ) . INTERVENTIONS The intervention lasted for 12 weeks , 3 times per week . The participants were r and omized into two groups : ( 1 ) squat training with whole-body vibration , and ( 2 ) squat training without vibration . RESULTS Although there was no statistical difference in functional performance and self-report of disease status between the groups , performance in all the functional tests and in all the domains of WOMAC improved in the vibration group compared to their initial status . In the exercise group , performance improved only two tests ( BBS and 6MWT ) , and there was a reduction in self-reported pain ( WOMAC ) compared to their initial status . CONCLUSIONS Although the addition of whole-body vibration to squat training failed to result in a significant improvement in functional performance and self-reported status of knee osteoarthritis in the elderly , the intragroup results suggest that whole-body vibration may represent a feasible and effective way of improving the functionality and self-perception of disease status in older adults with knee OA The purpose of this study was to assess the effect of whole body vibration ( WBV ) exercise on muscle strength and proprioception in female patients with osteoarthritis in the knee ( knee-OA ) . A single blinded , r and omised , controlled trial was performed in an outpatient clinic on 52 female patients diagnosed with knee-OA ( mean age 60.4 years+/-9.6 ) . They were r and omly assigned to one of 3 groups : 1 . WBV-exercise on a stable platform ( VibM ; n=17 ( mean age , 61.5+/-9.2 ) ) , WBV-exercise on a balance board ( VibF ; n=18 ( mean age , 58.7+/-11.0 ) ) , or control group ( Con ; n=18 ( mean age , 61.1+/-8.5 ) ) . The WBV groups trained twice a week for 8 weeks , with a progressively increasing intensity . The WBV groups performed unloaded static WBV exercise . The following were measured : knee muscle strength ( extension/flexion ) and proprioception ( threshold for detection of passive movement ( TDPM ) ) . Self-reported disease status was measured using WOMAC . It was found that muscle strength increased significantly ( p<0.001 ) in VibM compared to Con . Isometric knee-extension significantly increased ( p=0.021 ) in VibM compared to Con . TDPM was significantly improved ( p=0.033 ) in VibF compared Output:	Whole body vibration was not associated with a signiﬁcant reduction in Western Ontario and McMaster Universities index pain and stiffness score . Conclusion : Eight-week and 12-week whole body vibration is beneficial for improving physical functions in patients with knee osteoarthritis and could be included in rehabilitation programs
MS21931	*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: Zuclopenthixol acetate — a new injectable formulation with a duration of action of 2–3 days — was compared with conventional intramuscular and oral formulations of haloperidol and zuclopenthixol in the initial treatment of acutely disturbed , psychotic patients . The patients were stratified into 3 diagnostic categories : acute psychoses ( 48 patients ) , mania ( 22 patients ) , and exacerbation of chronic psychoses ( 73 patients ) . The patients were rated on the Brief Psychiatric Rating Scale ( BPRS ) , the Bech‐Rafaelsen Mania Rating Scale ( brmas ) ( only manic patients ) and globally on the Clinical Global Impression ( CGI ) . The study was an open , r and omized multicentre trial with a 6‐day treatment period . The zuclopenthixol acetate patients received 1–4 doses , the haloperidol patients 1–26 and the zuclopenthixol patients 1–22 doses . The assessment s on the CGI showed that all 3 treatments caused a clear reduction of the severity of illness scores in all 3 diagnostic categories , with no differences between treatments . The ratings of the acute and chronic psychotic patients on the BPRS also showed significant reductions in scores with no differences between treatments . All 3 treatments caused a rapid remission of symptoms on the BRMAS . Haloperidol induced hypokinesia in significantly more patients than zuclopenthixol acetate after 24 h. Later there were no significant differences between treatments . Zuclopenthixol acetate fulfils many desires for an amended neuroleptic formulation for the initial treatment of acutely disturbed psychotic patients 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 Poor neuroleptic response is a major unresolved clinical problem . Precise data concerning the frequency of poor neuroleptic response are not available . The implementation of treatment modalities that are specifically recommended for non‐responders ( such as clozapine ) increases the desirability of such data . This study evaluated the proportion of acutely exacerbated schizophrenics who remained unimproved by consecutive administration of haloperidol , chlorpromazine and perphenazine , in r and omly determined order . The overall improvement rate was 95 % . The frequency of good responses to the first , second and third drug were 67 % , 55 % , and 67 % respectively . Differences in receptor affinity profile might explain the added beneficial effect of a second or third drug Forty acutely psychotic patients were treated either with flupenthixol drops or haloperidol drops in an open , 28-day controlled study . The flupenthixol group comprised 11 schizophrenic , 8 manic , and 1 paranoid patient and there were 10 schizophrenic , 5 manic , and 5 paranoid patients in the haloperidol group . Mean daily dosage was approximately 112 mg flupenthixol and 18 mg haloperidol . Clinical ly , both drugs showed an antipsychotic effect . In the schizophrenic patients there was a definite trend towards a more rapid relief of the psychotic symptoms after flupenthixol treatment . In contrast to haloperidol , flupenthixol showed a mood elevating effect and an effect on the negative symptoms , e.g. emotional withdrawal , motor retardation , blunted affect , and disorientation . With both drugs , the most troublesome side-effects were extrapyramidal in nature . Initially , they were more common in the flupenthixol group : later the incidence was similar The relative efficacy of 4 tranquilizers was investigated in 66 chronic schizophrenics who had been hospitalized for 10.01 years ( mean ) . The role of adding an anti-depressant was also studied . Following a 4 week placebo period , high dosage tranquilizers were given for 16 weeks and amitriptyline was added for the following 16 weeks . Statistical analyses of the various change measures revealed that patients worsened significantly on placebo , all 4 tranquilizers were significantly better than placebo for symptom reduction and maximum improvement was attained within 16 weeks of tranquilizer administration . No significant differences in efficacy were observed among the 4 tranquilizers and addition of amitriptyline did not confer any additional therapeutic advantage Subjects Thirty-four newly admitted acute schizophrenic patients were studied : they included first admissions and others undergoing acute exacerbations with a history of previous acute schizophrenic episodes . None of these patients had received tranquillizing medication for at least one month prior to admission to hospital , or electroconvulsive therapy for at least two months . They ranged in age from seventeen to fifty-four years with a mean age of thirty-four . Some preliminary . findings with the first twenty subjects in this series have already been published ( 4 ) . coefficient of variation ( CV ) than the other fifty-five patients who were receiving a variety of drugs . The procedure described here permitted a more detailed analysis of the effects of two antipsychotic agents ( quite different in chemical structure ) upon the integrated EEG measures in a more systematic comparative design of shortterm drug effects . It also permitted a comparison of effects , both clinical and EEG , over a time period ( seven days ) similar to that in which the clinician might ordinarily decide whether his patient was showing satisfactory response , leading him to continue a particular antipsychotic compound or switch to another An experimental method was utilized to compare the masking effects of two neuroleptic agents -- molindone and haloperidol -- on 18 neuroleptic-treated schizophrenic patients exhibiting operationally defined withdrawal-exacerbated tardive dyskinesia . After a week on one of these two medications at preestablished doses equivalent to that of the pre- study neuroleptic , molindone-masked total AIMS scores by significantly less ( 12 % ) than haloperidol ( 27 % ) . Similarly , during a second week when the dose of these neuroleptics was equivalent to 200 % that of the pre- study dose , molindone masked the total AIMS score significantly less ( 23 % ) as compared to haloperidol ( 53 % ) . Several interpretations of this finding are considered . This study demonstrates the feasibility of a method that may offer a model for underst and ing pharmacological differences among neuroleptic medications Remitted schizophrenic out patients were treated in order to prevent relapse with three doses of haloperidol or propericiazine for 1 year in a double-blind controlled study employing a r and omized design . The drug 's ability to prevent relapse was evaluated by counting the number of symptom-free days for each patient before any sign of relapse or over-dose appeared . Patients were r and omly assinged to the following drugs orally administered once per day at night : placebo ; haloperidol 1 mg , 3 mg , and 6 mg ; propericiazine 10 mg , 30 mg , and 60 mg . Serum prolactin levels in each patient were estimated by radioimmunoassay . All patients treated with placebo relapsed within 1 year and the relapse rate with placebo was significantly higher than with any dose of the two neuroleptics . Haloperidol increased the number of symptom-free days in a dose-dependent manner . Propericiazine at 10 mg and 30 mg also increased the number of symptom-free days dose-dependently but at 60 mg , the number decreased . It appears that propericiazine shows an inverted U-shaped dose-response curve . Prolactin levels were elevated dose-dependently by both drugs but failed to show a significant correlation with the number of symptom-free days . The present results indicate that haloperidol is superior to propericiazine from the viewpoint of the wider “ therapeutic window ” in maintenance treatment and antidopaminergic properties of neuroleptics , wherein it is important to prevent relapse even in remitted schizophrenics BACKGROUND Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia ; however , their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated . We aim ed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol , in first-episode schizophrenia . METHODS We did an open r and omised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites , in 14 countries . Eligible patients were aged 18 - 40 years , and met diagnostic criteria for schizophrenia , schizophreniform disorder , or schizoaffective disorder . 498 patients were r and omly assigned by a web-based online system to haloperidol ( 1 - 4 mg per day ; n=103 ) , amisulpride ( 200 - 800 mg per day ; n=104 ) , olanzapine ( 5 - 20 mg per day ; n=105 ) , quetiapine ( 200 - 750 mg per day ; n=104 ) , or ziprasidone ( 40 - 160 mg per day ; n=82 ) ; follow-up was at 1 year . The primary outcome measure was all-cause treatment discontinuation . Patients and their treating physicians were not blinded to the assigned treatment . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N68736636 . FINDINGS The number of patients who discontinued treatment for any cause within 12 months was 63 ( Kaplan-Meier estimate 72 % ) for haloperidol , 32 ( 40 % ) for amisulpride , 30 ( 33 % ) for olanzapine , 51 ( 53 % ) for quetiapine , and 31 ( 45 % ) for ziprasidone . Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride ( hazard ratio [ HR ] 0.37 , [ 95 % CI 0.24 - 0.57 ] ) , olanzapine ( HR 0.28 [ 0.18 - 0.43 ] ) , quetiapine ( HR 0.52 [ 0.35 - 0.76 ] ) , and ziprasidone ( HR 0.51 [ 0.32 - 0.81 ] ) . However , symptom reductions were virtually the same in all the groups , at around 60 % . INTERPRETATION This pragmatic trial suggests that clinical ly meaningful antipsychotic treatment of first-episode of schizophrenia is achievable , for at least 1 year . However , we can not conclude that second-generation drugs are more efficacious than is haloperidol , since discontinuation rates are not necessarily consistent with symptomatic improvement The schizophrenic patient 's early psychological response to neuroleptic treatment has been demonstrated to be a significant predictor of treatment response . The validity of the construct of subjective response is evaluated by comparison of two measures . Fifty-five recently admitted and unmedicated schizophrenic patients were r and omly allocated to chlorpromazine or haloperidol . Subjective responses at 24 and 48 hours as assessed by two different scales , the Van Putten & May scale and the self-administered Drug Attitude Inventory , were strongly correlated with outcome at three weeks . Early emergence of extrapyramidal symptoms was not related to subjective response , but dysphoric patients had a greater incidence of EPS by the end of treatment than did non-dysphoric patients . The two measures showed high concordance in identification of early drug dysphoria Neurochemical distinctions have been made between neuroleptic drugs that affect D-1 receptors as well as D-2 receptors , compared with those neuroleptic drugs that affect only D-2 receptors . However , a controlled double-blind study of haloperidol vs. chlorprothixene in schizophrenic patients found no significant differences BACKGRO Output:	There were no significant differences for discontinuation rates .
MS21932	*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: Two hundred Hausa primigravidae at Zaria were divided into five groups in a r and omized double-blind trial of antenatal oral antimalarial prophylaxis , and haematinic supplements . Group 1 received no active treatment . Groups 2 to 5 were given chloroquine 600 mg base once , followed by proguanil 100 mg per day . In addition , group 3 received iron 60 mg daily , group 4 folic acid 1 mg daily , and group 5 iron plus folic acid . Forty-five percent were anaemic ( haemoglobin ( Hb ) less than 11.0 g dl-1 ) at first attendance before 24 weeks of gestation , and malaria parasitaemia ( predominantly Plasmodium falciparum ) was seen in 27 % , of whom 60 % were anaemic . The mean Hb fell during pregnancy in group 1 , and seven patients in this group had to be removed from the trial and treated for severe anaemia ( packed cell volume ( PCV ) less than 0.26 ) . Only five patients in the other groups developed severe anaemia ( P = 0.006 ) , two of whom had malaria following failure to take treatment . Patients in group 1 had the lowest mean Hb at 28 and 36 weeks of gestation , and patients receiving antimalarials and iron ( groups 3 and 5 ) had the highest Hb at 28 weeks , but differences were not significant , possibly due to removal from the trial of patients with severe anaemia . Anaemia ( Hb less than 12.0 g dl-1 ) at six weeks after delivery was observed in 61 % of those not receiving active treatment ( group 1 ) , in 39 % of those protected against malaria but not receiving iron supplements ( groups 2 and 4 ) and in only 18 % of patients receiving both antimalarials and iron ( groups 3 and 5 ) . Folic acid had no significant effect on mean Hb . Proguanil was confirmed to be a highly effective causal prophylaxis . Prevention of malaria , without folic acid supplements , reduced the frequency of megaloblastic erythropoiesis from 56 % to 25 % . Folic acid supplements abolished megaloblastosis , except in three patients who were apparently not taking the treatment prescribed . Red cell folate ( RCF ) concentrations were higher in subjects with malaria , probably due to intracellular synthesis by plasmodia . Infants of mothers not receiving antimalarials appeared to have an erythroid hyperplasia . Maternal folate supplements raised infants ' serum folate and RCF . Fourteen per cent had low birth weight ( less than 2500 g ) , and the perinatal death rate was 11 % ; the greatest number were in group 1 , but not significantly . A regime is proposed for the prevention of malaria , iron deficiency , folate deficiency and anaemia in pregnancy in the guinea savanna of Nigeria To determine the effect of chloroquine chemoprophylaxis during pregnancy on birth weights , a r and omized trial was carried out in 1987 and 1988 in Banfora , Burkina Faso ( West Africa ) . Seven hundred forty-five r and omly selected women treated with chloroquine sulfate were compared to with 719 controls who received no treatment . In spite of an un question able effect of chloroquine in preventing placental infection ( 4.1 % infected placentas in the treated group versus 19.0 % in the controls ) , the mean difference in birth weights between the two groups ( 6 g ) was not significant . The difference in the proportion of low birth weight ( LBW ) newborn babies in two groups ( 16.3 % versus 16.4 % ) was also not significant . However , there was a strong relationship between placental infection and birth weight ( the mean birth weight difference between infected and uninfected placentas was 113 g , and the proportion of LBW babies was 26.0 % in infected placentas versus 14.8 % in uninfected placentas ) . The small difference in birth weights observed between the two groups may be due to the fact that the prevalence rate of placental infection is low and that prophylaxis is effective only on a portion of the subjects in the treated group . It may also indicate that malaria is only one of several risk factors responsible for LBW . The relatively small increase in birth weight , the expected poor acceptance of mass prophylaxis , and the spreading of chloroquine-resistant Plasmodium strains should be considered before extending malaria chemoprophylaxis to all pregnant women . It might be worth considering to limit prophylaxis to primigravidae BACKGROUND In areas of endemic transmission , malaria in pregnancy is associated with severe maternal anaemia and low-birthweight babies . We studied the efficacy of intermittent treatment doses of sulphadoxine-pyrimethamine in preventing malaria and severe anaemia in pregnancy in a double-blind placebo-controlled trial among primigravid women living in Kilifi District , Kenya . METHODS Between January , 1996 , and April , 1997 , 1264 primigravid women were recruited when they attended for antenatal care , and r and omly assigned sulphadoxine-pyrimethamine ( 640 ) or placebo ( 624 ) . Women received one , two , or three doses of study medication depending on the duration of gestation at enrolment . Primary outcome measures were severe anaemia ( haemoglobin < 8 g/dL ) and malaria parasitaemia , assessed at 34 weeks of gestation . Analyses were based on intention to treat among women who had study blood tests at 34 weeks . FINDINGS 30 ( 5.3 % ) of 567 women in the sulphadoxine-pyrimethamine group and 199 ( 35.3 % ) of 564 in the placebo group had peripheral parasitaemia ( protective efficacy 85 % [ 95 % CI 78 - 90 ] , p<0.0001 ) . 82 ( 14.5 % ) and 134 ( 23.7 % ) had severe anaemia ( protective efficacy 39 % [ 22 - 52 ] , p<0.0001 ) . Even women who booked late and received only one dose of sulphadoxine-pyrimethamine benefited significantly from the intervention . The effects were seen both in women who owned insecticide-treated bednets and in women who did not . INTERPRETATION Intermittent presumptive treatment with sulphadoxine-pyrimethamine is an effective , practicable strategy to decrease the risk of severe anaemia in primigravidae living in malarious areas The effectiveness of insecticide-treated bednets ( ITBN ) in preventing malaria and anaemia among primigravidae living in Kilifi District , Kenya , was assessed by a r and omized controlled trial between September 1994 and November 1995 . All residents within 28 community clusters received ITBN in July 1993 , whilst residents of another 28 clusters served as contemporaneous controls . All resident primigravid women with singleton pregnancies attending antenatal care at Kilifi District Hospital were eligible for recruitment . 503 primigravidae were recruited . 91.4 % were anaemic antenatally ( Hb < 11 g/dl ) : 91.0 % from the intervention arm and 92.0 % from the control arm . Severe anaemia ( Hb < 7 g/dl ) was found among 15.1 % of intervention women and 20.1 % of control women ( P = 0.28 ) . No significant differences were observed in reports of febrile illness or the presence of chloroquine in the serum or peripheral parasitaemia during the third trimester between the two groups . In the women delivering in hospital ( n = 130 ) , there was no association between placental malaria infection and the intervention : 77.4 % of placentas from control women had evidence of past or active infection , compared with 72.0 % of placentas from intervention women ( P = 0.76 ) . Similarly , in the women delivering in hospital , ITBN did not improve birth weight , and there were no differences in perinatal mortality between the two study groups . Despite ITBN having a great impact on paediatric severe malaria and mortality in this transmission setting , there was very little impact of ITBN on the morbidity associated with malaria infection in primigravidae . Alternative strategies are required to tackle this continued public health problem for pregnant women living in endemic areas similar to the Kenyan Coast A r and omized trial was carried out from 1991 to 1993 among women attending an antenatal clinic in Ebolowa , Cameroon where malaria is hyperendemic and transmission occurs at a high level all year round . All pregnant women attending the clinic for their first prenatal visit between October 1991 and November 1992 were alternately assigned to chloroquine ( CQ ) or control ( CT ) groups . Chloroquine was given under observation at a weekly oral dose of 300 mg . At delivery , smears from maternal , cord , and placental blood were made and stained with Giemsa for parasites . An in vivo chloroquine sensitivity investigation was carried out on women attending the postnatal consultation to evaluate the level of chloroquine resistance in the target population . The efficacy of chloroquine was moderate in placental infection ( 39.2 % infected in the CQ group versus 57.8 % in the CT group : P = 0.05 ) , probably because of a resistance to chloroquine estimated to be 10.9 % . In the CQ group , the mean birth weight was significantly higher ( P = 0.02 ) and the proportion of low birth weight newborns was lower ( 10.5 % versus 27.7 % ; P = 0.02 ) . A strong correlation between placental infection and birth weight was observed : the mean birth weight difference between infected and noninfected placentae was 359 g ( P < 0.0001 ) and the proportion of low birth weight new born babies was 35.6 % versus 5.9 % ( P = 0.0001 ) . In Cameroon , in spite of a moderate resistance to chloroquine , this drug proved to be highly effective in increasing birth weight when administered to primigravidae . We therefore think such a prophylaxis should be recommended only to primigravidae in high transmission areas To define an effective and deliverable antimalarial regimen for use during pregnancy , pregnant women at highest risk of malaria ( those in their first or second pregnancy ) in an area of Malawi with high transmission of chloroquine (CQ)-resistant Plasmodium falciparum were placed on CQ and /or sulfadoxine-pyrimethamine ( SP ) . Of 38 pregnant women who received CQ treatment followed by weekly CQ prophylaxis ( CQ/CQ ) for at least 45 days prior to delivery , 32 % had placental malaria infection , compared with 26 % of 50 pregnant women who received a treatment dose of SP followed by weekly CQ prophylaxis ( SP/CQ ) , and only 9 % of 71 pregnant women who received a two-dose SP regimen ( SP/SP ; given once during the second trimester and repeated at the beginning of the third trimester ) ( P = 0.006 , by chi-square test ) . During the peak transmission season from April to July , 47 % of the women who received CQ/CQ had placental malaria infection at delivery , as compared with 37 % of the women who received SP/CQ , and 10 % of women who received SP/SP ( P = 0.004 , by chi-square test ) . Among women in their first or second pregnancy , two treatment doses of SP were highly effective in decreasing the proportion of women with placental malaria infection at delivery A r and omized , double blind , placebo-controlled community based trial of Maloprim ( pyrimethamine 12.5 mg+dapsone 100 mg ) administered to primigravid pregnant women by Traditional Birth Attendants was carried out in a rural area of The Gambia , West Africa . Placental histology showed less malaria infection in women who received chemoprophylaxis than in those who received placebo . The birth weight of children born to women who received chemoprophylaxis was increased by an average of 153 g. Within the treatment groups , there were no significant differences in the birthweights of babies born to women who had histological evidence of malaria infection of the placenta compared to those who had no malaria infection . This study confirms the beneficial effect of malaria prophylaxis for primigravid pregnant women but questions the mechanism by which malaria affects foetal development The safety of daily application of N , N-diethyl-m-toluamide ( DEET ) ( 1.7 g of DEET/day ) in the second and third trimesters of pregnancy was assessed as part of a double-blind , r and omized , therapeutic trial of insect repellents for the prevention of malaria in pregnancy ( n = 897 ) . No adverse neurologic , gastrointestinal , or dermatologic effects were observed for women who applied a median total dose of 214.2 g of DEET per pregnancy ( range = 0 - 345.1 g ) . DEET crossed the placenta and was detected in 8 % ( 95 % confidence interval = 2.6 - 18.2 ) of cord blood sample s from a r and omly selected subgroup of DEET users ( n = 50 ) . No adverse effects on survival , growth , or development at birth , or at one year , were found . This is the first study to Output:	REVIEW ER 'S CONCLUSIONS Drugs given routinely for malaria during pregnancy reduce severe antenatal anaemia in the mother , and are associated with higher birthweight and probably reduced perinatal mortality . This effect appears to be limited to low parity women
MS21933	*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 . Few studies have investigated the efficacy of antiretroviral therapy among HIV-infected children in re source -poor setting s. This observational , retrospective analysis describes the clinical , immunologic , and virologic effects of highly active antiretroviral therapy in treatment-naive , HIV-infected children in Mombasa , Kenya . In keeping with a public health approach , all children were treated by using a simplified , nationally approved , triple-drug regimen . METHODS . Clinical data and stored plasma sample s from 29 children who were followed prospect ively between April 2003 and October 2004 were analyzed . All children received generic formulations of nevirapine , zidovudine , and lamivudine and were evaluated at baseline and at 3 , 6 , 9 , 12 , and 15 months . At each visit , weight and CD4 lymphocyte counts were measured and plasma sample s were stored for analysis . HIV RNA load was determined retrospectively at baseline and 9 months after initiation of therapy . RESULTS . The mean age of the children was 8.5 years ( range : 2–16 years ) . At baseline , the mean CD4 count ( ±SD ) was 182.3 × 106 cells per μL ( ±145.6 ) . On treatment , CD4 counts increased step-wise by a mean of 187 × 106 cells per μL at 3 months , 293 cells per μL at 6 months , 308 cells per μL at 9 months , 334 cells per μL at 12 months , and 363 cells per μL at 15 months . The mean plasma viral load decreased from a baseline level of 622 712 to 35369 copies per mL , and at 9 months was undetectable in 55 % of the patients . Mean z scores for weight for age increased from a baseline of −1.61 to −1.12 at 12 months into therapy . CONCLUSIONS . A public health approach using 1 treatment regimen in generic form showed excellent efficacy among treatment-naive , HIV-infected children in a re source -limited country . Clinical and immunologic improvement occurred in all patients , but 9 months after the start of therapy , only 55 % of the children had an undetectable viral load BACKGROUND Data are limited about the effectiveness of pediatric antiretroviral therapy ( ART ) in low-income countries . METHODS We report the outcomes of consecutively treating 236 human immunodeficiency virus type 1 (HIV-1)-infected treatment-naive children with triple ART in Port-au-Prince , Haiti , between 1 May 2003 and 30 April 2006 . RESULTS Kaplan-Meier survival analysis at follow-up demonstrated that 191 children ( 81 % ) remained in care , 21 ( 9 % ) were dead , and 24 ( 10 % ) were lost to follow-up . Independent baseline predictors of mortality were age < 18 months , CD4(+ ) T cell percentage < or = 5 % , and weight-for-age Z score ( WAZ ) less than -3 . Twelve months into ART , 56 % of tested subjects had undetectable HIV-1 RNA loads . Median CD4(+ ) T cell percentages at 12 months increased by 15 % , 11 % , and 5 % in children with baseline percentages of < or = 5 % , 6%-24 % , and > or = 25 % , respectively ( P<.01 ) . The median WAZ at 12 months increased by 1.0 , 0.6 , and 0.2 in children with baseline WAZ less than -2 , -2 to -1.1 , and -1 or more , respectively ( P<.01 ) . CONCLUSION With continuous donor support , trained providers , and the availability of pediatric antiretroviral drug formulations , it proved feasible to deliver pediatric ART in Haiti . The effectiveness of this program should encourage efforts to make ART available for HIV-infected children in poor countries Background There are limited data of immunologic and virologic failure in Asian HIV-infected children using non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy ( HAART ) . We examined the incidence rate of immunologic failure ( IF ) and virologic failure ( VF ) and the accuracy of using IF to predict VF in Thai HIV-infected children using first-line NNRTI-based HAART . Methods Antiretroviral (ART)-naïve HIV-infected children from 2 prospect i ve cohorts treated with NNRTI-based HAART during 2001 - 2008 were included . CD4 counts were performed every 12 weeks and plasma HIV-RNA measured every 24 weeks . Immune recovery was defined as CD4%≥25 % . IF was defined as persistent decline of ≥5 % in CD4 % in children with CD4%<15 % at baseline or decrease in CD4 count ≥30 % from baseline . VF was defined as HIV-RNA>1,000 copies/ml after at least 24 weeks of HAART . Clinical and laboratory parameter changes were assessed using a paired t-test , and a time to event approach was used to assess predictors of VF . Sensitivity and specificity of IF were calculated against VF . Results 107 ART-naive HIV-infected children were included , 52 % female , % CDC clinical classification N : A : B : C 4:44:30:22 % . Baseline data were median ( IQR ) age 6.2 ( 4.2 - 8.9 ) years , CD4 % 7 ( 3 - 15 ) , HIV-RNA 5.0 ( 4.9 - 5.5 ) log10copies/ml . Nevirapine ( NVP ) and efavirenz (EFV)-based HAART were started in 70 % and 30 % , respectively . At 96 weeks , none had progressed to a CDC clinical classification of AIDS and one had died from pneumonia . Overall , significant improvement of weight for age z-score ( p = 0.014 ) , height for age z-score , hemoglobin , and CD4 were seen ( all p < 0.001 ) . The median ( IQR ) CD4 % at 96 weeks was 25 (18 - 30)% . Eighty-nine percent of children had immune recovery ( CD4%≥25 % ) and 75 % of children had HIV-RNA < 1.7log10copies/ml . Thirty five ( 32.7 % ) children experienced VF within 96 weeks . Of these , 24 ( 68.6 % ) and 31 ( 88.6 % ) children had VF in the first 24 and 48 weeks respectively . Only 1 ( 0.9 % ) child experienced IF within 96 weeks and the sensitivity ( 95%CI ) of IF to VF was 4 (0.1 - 20.4)% and specificity was 100 (93.9 - 100)% . Conclusion Immunologic failure , as defined here , had low sensitivity compared to VF and should not be recommended to detect treatment failure . Plasma HIV-RNA should be performed twice , at weeks 24 and 48 , to detect early treatment failure . Trial Registration Clinical trials.gov identification BACKGROUND Nevirapine-based antiretroviral therapy is the predominant ( and often the only ) regimen available for children in re source -limited setting s. Nevirapine resistance after exposure to the drug for prevention of maternal-to-child human immunodeficiency virus ( HIV ) transmission is common , a problem that has led to the recommendation of ritonavir-boosted lopinavir in such setting s. Regardless of whether there has been prior exposure to nevirapine , the performance of nevirapine versus ritonavir-boosted lopinavir in young children has not been rigorously established . METHODS In a r and omized trial conducted in six African countries and India , we compared the initiation of HIV treatment with zidovudine , lamivudine , and either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 2 to 36 months of age who had no prior exposure to nevirapine . The primary end point was virologic failure or discontinuation of treatment by study week 24 . RESULTS A total of 288 children were enrolled ; the median percentage of CD4 + T cells was 15 % , and the median plasma HIV type 1 ( HIV-1 ) RNA level was 5.7 log(10 ) copies per milliliter . The percentage of children who reached the primary end point was significantly higher in the nevirapine group than in the ritonavir-boosted lopinavir group ( 40.8 % vs. 19.3 % ; P<0.001 ) . Among the nevirapine-treated children with virologic failure for whom data on resistance were available , more than half ( 19 of 32 ) had resistance at the time of virologic failure . In addition , the time to a protocol -defined toxicity end point was shorter in the nevirapine group ( P=0.04 ) , as was the time to death ( P=0.06 ) . CONCLUSIONS Outcomes were superior with ritonavir-boosted lopinavir among young children with no prior exposure to nevirapine . Factors that may have contributed to the suboptimal results with nevirapine include elevated viral load at baseline , selection for nevirapine resistance , background regimen of nucleoside reverse-transcriptase inhibitors , and the st and ard ramp-up dosing strategy . The results of this trial present policymakers with difficult choices . ( Funded by the National Institute of Allergy and Infectious Diseases and others ; P1060 Clinical Trials.gov number , NCT00307151 . ) Growth failure is a common problem in HIV-infected children . The extent to which this growth failure could be reversed after the children receive antiretroviral therapy ( ART ) is not known . This study assessed the incidence of growth failure in HIV-infected Thai children , impact of ART on growth , and the predictors of growth reversal after initiating ART . Growth parameters and other characteristics were extracted from the data base of a prospect i ve cohort of HIV-infected children ( age < or=15 years ) who were enrolled to initiate non-nucleoside reverse transcriptase inhibitor-based ART between August 2002 and May 2007 . Body weight and height measurements , CD4 cell counts , plasma HIV RNA levels were collected at baseline and 24-week intervals . A total of 225 HIV-infected children were included , 116 ( 51 % ) were males . The median age at baseline was 7.4 years ( interquartile range [ IQR ] 5.2 - 9.8 ) . Fifty-three percent were in Centers for Disease Control and Prevention ( CDC ) category C and 54 % had CD4 percentage 5 or less . The mean ( st and ard deviation [ SD ] ) of baseline weight-for-age ( WAZ ) and height-for-age ( HAZ ) z-scores were -2.02 ( 1.17 ) and -2.22 ( 1.51 ) . The median follow-up time was 216 weeks ( IQR 120 - 240 ) . The cumulative probability of growth reversal among the 179 subjects with growth failure at entry was 58 % ( 95 % confidence interval [ CI ] 49 - 67 ) at week 240 . In a multivariate Cox regression model , higher entry WAZ ( p < 0.001 ) and HAZ ( p < 0.001 ) , use of a nevirapine-based regimen ( compared to efavirenz , p = 0.027 ) and larger CD4 % gains to week 48 ( p < 0.001 ) were significant predictors of growth reversal after initiating ART . NNRTI-based ART leads to a substantial improvement in growth of HIV-infected children . Initiation of ART before the children developed growth failure should be encouraged OBJECTIVE To describe the outcomes of antiretroviral therapy ( ART ) in a large cohort of HIV-infected children in Thail and . METHODS The data were obtained from four collaborative referral sites around the country . Data from 2008 to March 2011 were collected prospect ively , and data before 2008 were collected retrospectively . RESULTS Of the 1139 children , 599 ( 52.6 % ) were female , and the duration of ART was a median 2.9 years ( interquartile range ( IQR ) 3.3 - 5.5 years ) . At ART initiation , the median age was 7.1 years ( IQR 3.4 - 10.0 years ) , CD4 percentage was 9.0 % ( IQR 3.0 - 17.0 % ) , and 61.3 % were in World Health Organization ( WHO ) stage 3 or 4 . Seventy-four percent were initiated on an NNRTI-based regimen . The death and lost to follow-up rates were 1.3 ( 95 % confidence interval ( CI ) 1.1 - 1.6 ) and 2.2 ( 95 % CI 1.6 - 2.6)/100 patient-years of follow-up , respectively . At the last clin Output:	Younger cohort age was associated with greater growth reconstitution . Protease inhibitor and nonnucleoside reverse-transcriptase inhibitor regimens yielded comparable growth . Supplement benefits were attenuated after adjusting for baseline cohort growth . RLS children had substantial growth deficits compared with developed setting s counterparts at ART ; growth shortfalls in RLS persisted despite reconstitution . Earlier age and nutritional supplementation at ART may improve growth outcomes .
MS21934	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To assess the impact , retention , and magnitude of effect of a required didactic and experiential palliative care curriculum on third-year medical students ' knowledge , confidence , and concerns about end-of-life care , over time and in comparison to benchmark data from a national study of internal medicine residents and faculty . DESIGN Prospect i ve study of third-year medical students prior to and immediately after course completion , with a follow-up assessment in the fourth year , and in comparison to benchmark data from a large national study . SETTING Internal Medicine Clerkship in a public accredited medical school . PARTICIPANTS Five hundred ninety-three third-year medical students , from July 2002 to December 2007 . MAIN OUTCOME MEASURES Pre- and postinstruction performance on : knowledge , confidence ( self-assessed competence ) , and concerns ( attitudes ) about end-of-life care measures , vali date d in a national study of internal medicine residents and faculty . Medical student 's reflective written comments were qualitatively assessed . INTERVENTION Required 32-hour didactic and experiential curriculum , including home hospice visits and inpatient hospice care , with content drawn from the AMA-sponsored Education for Physicians on End-of-life Care ( EPEC ) Project . RESULTS Analysis of 487 paired t tests shows significant improvements , with 23 % improvement in knowledge ( F(1,486)=881 , p<0.001 ) , 56 % improvement in self-reported competence ( F(1,486)=2,804 , p<0.001 ) , and 29 % decrease in self-reported concern ( F(1,486)=208 , p<0.001 ) . Retesting medical students in the fourth year showed a further 5 % increase in confidence ( p<0.0002 ) , 13 % increase in allaying concerns ( p<0.0001 ) , but a 6 % drop in knowledge . The curriculum 's effect size on M3 students ' knowledge ( 0.56 ) exceeded that of a national cross-sectional study comparing residents at progressive training levels ( 0.18 ) Themes identified in students ' reflective comments included perceived relevance , humanism , and effectiveness of methods used to teach and assess palliative care education . CONCLUSIONS We conclude that required structured didactic and experiential palliative care during the clinical clerkship year of medical student education shows significant and largely sustained effects indicating students are better prepared than a national sample of residents and attending physicians Background By 2013 Palliative Care will become a m and atory examination subject in the medical curriculum in Germany . There is a pressing need for effective and well- design ed curricula and assessment methods . Debates are on going as how Undergraduate Palliative Care Education ( UPCE ) should be taught and how knowledge and skills should be assessed . It is evident by this time that the development process of early curricula in the US and UK has led to a plethora of diverse curricula which seem to be partly ineffective in improving the care for the seriously ill and dying offered by newly qualified doctors , as is demonstrated in controlled evaluations . The goals of this study were to demonstrate an evidence -based approach towards developing UPCE curricula and investigate the change in medical students ’ self-perceived readiness to deal with palliative care patients and their families . Methods To evaluate the effects of the UPCE curriculum we chose a prospect i ve , controlled , quasi-experimental , pre , retrospective-pre , post study design . A total of n = 37 3rd and 4th –year medical students were assigned to the intervention group ( n = 15 ; 4th -year ) and to the control group ( n = 22 ; 3rd-year ) . Resting on the self-efficacy concept of B and ura the measurement was conducted by a refined test-battery based on two independent measurements ( the revised Collet-Lester-Fear-of-Death-Scale and the instrument of the “ Program in Palliative Care Education and Practice ” at Harvard Medical School ) including 68 items altogether in a five-point Likert-scale . These items were design ed to test elementary skills in caring for the dying and their relatives as perceived by medical undergraduates . Data sets from both groups were analysed by paired and independent two- sample t-test . The TREND statement for reporting non-r and omized evaluations was applied for reporting on this quasi-experimental study . Results Three constructs showed statistically significant differences comparing the intervention group before and after . Willingness to accompany a dying patient increased from 21.40 to 37.30 ( p < .001 ) . Self-estimation of competence in communication with dying patients and their relatives increased from 12.00 to 23.60 ( p = .001 ) . Finally , self-estimation of knowledge and skills in Palliative Care increased from 8.30 to 13.20 ( p = .001 ) . Conclusions This study is a small but systematic step towards rigorous curricular development in palliative care . Our manualised curriculum is available for scrutiny and scientific feedback to support an open and constructive process of best- practice comparison in palliative care OBJECTIVE : To assess the status of medical education in end-of-life care and identify opportunities for improvement . DESIGN : Telephone survey . SETTING : U.S. academic medical centers . PARTICIPANTS : National probability sample of 1,455 students , 296 residents , and 287 faculty ( response rates 62 % , 56 % , and 41 % , respectively ) affiliated with a r and om sample of 62 accredited U.S. medical schools . MEASUREMENTS AND MAIN RESULTS : Measurements assessed attitudes , quantity and quality of education , preparation to provide or teach care , and perceived value of care for dying patients . Ninety percent or more of respondents held positive views about physicians ’ responsibility and ability to help dying patients . However , fewer than 18 % of students and residents received formal end-of-life care education , 39 % of students reported being unprepared to address patients ’ fears , and nearly half felt unprepared to manage their feelings about patients ’ deaths or help bereaved families . More than 40 % of residents felt unprepared to teach end-of-life care . More than 40 % of respondents reported that dying patients were not considered good teaching cases , and that meeting psychosocial needs of dying patients was not considered a core competency . Forty-nine percent of students had told patients about the existence of a life-threatening illness , but only half received feedback from residents or attendings ; nearly all residents had talked with patients about wishes for end-of-life care , and 33 % received no feedback . CONCLUSIONS : Students and residents in the United States feel unprepared to provide , and faculty and residents unprepared to teach , many key components of good care for the dying . Current educational practice s and institutional culture in U.S. medical schools do not support adequate end-of-life care , and attention to both curricular and cultural change are needed to improve end-of-life care education Prompted by directives from the GMC , ‘ care of the dying ’ is identified as ‘ core curricula ’ for undergraduate medical education . However , there are many technical and interpersonal challenges faced in learning the practice of palliative medicine . Accordingly , the design and delivery of education programmes need to be both carefully considered and evaluated . Using B and ura ’s Social Cognitive Theory as a driver , appropriate methodology for evaluating a novel education programme in palliative medicine was drafted . A pre- and post-survey of an education programme and palliative care placement for fourth year medical undergraduate students from Liverpool University ( n = 216 ) was completed using a composite question naire containing ; i ) Self-efficacy in Palliative Care Scale ( SEPC ) and ii ) Thanatophobia Scale . Both scales have shown reliability and validity within the sample population . Additionally , a r and omly selected Focus Group was conducted to provide qualitative information on the students ’ experience . A total of 139 pre- and post- question naires ( 64 % ) were completed . Analysis identified significant improvements in perceived efficacy ( SEPC Communication t = −16.41 , P < 0.001 ; SEPC Patient Management t = −22.31 , P < 0.001 ; SEPC Multidisciplinary Teamwork t = −15.56 , P < 0.001 ) . Significant improvements in thanatophobia were also recorded ( z = −7.51 , P < 0.001 ) although some interesting anomalies were noted . This study demonstrates that considered and appropriately structured clinical education has been shown to significantly improve students ’ belief in their ability to practice palliative medicine and to improve their attitude towards care . In accordance with the study ’s theoretical driver , it is reasonable to propose that the engaged active learning will have a positive effect on the future care of dying patients Purpose Few studies have compared the effect of Web-based eLearning versus small-group learning on medical student outcomes . Palliative and end-of-life ( PEOL ) education is ideal for this comparison , given uneven access to PEOL experts and content nationally . Method In 2010 , the authors enrolled all third-year medical students at the University of California , Davis School of Medicine into a quasi-r and omized controlled trial of Web-based interactive education ( eDoctoring ) compared with small-group education ( Doctoring ) on PEOL clinical content over two months . Students participated in three 3-hour PEOL sessions with similar content . Outcomes included a 24-item PEOL-specific self-efficacy scale with three domains ( diagnosis/treatment [ Cronbach alpha = 0.92 ; CI : 0.91–0.93 ] , communication/prognosis [ alpha = 0.95 ; CI : 0.93–0.96 ] , and social impact/self-care [ alpha = 0.91 ; CI : 0.88–0.92 ] ) ; 8 knowledge items ; 10 curricular advantage/disadvantages ; and curricular satisfaction ( both students and faculty ) . Results Students were r and omly assigned to Web-based eDoctoring ( n = 48 ) or small-group Doctoring ( n = 71 ) curricula . Self-efficacy and knowledge improved equivalently between groups ( e.g. , prognosis self-efficacy , 19 % ; knowledge , 10%–42 % ) . Student and faculty ratings of the Web-based eDoctoring curriculum and the small-group Doctoring curriculum were equivalent for most goals , and overall satisfaction was equivalent for each , with a trend toward decreased eDoctoring student satisfaction . Conclusions Findings showed equivalent gains in self-efficacy and knowledge between students participating in a Web-based PEOL curriculum in comparison with students learning similar content in a small-group format . Web-based curricula can st and ardize content presentation when local teaching expertise is limited , but it may lead to decreased user satisfaction Purpose . To describe attitudes and practice s of end-of-life care teaching in the undergraduate medical curriculum in the United States as reported by administrative leadership and identify opportunities for improvement . Method . A telephone survey of associate deans for medical education or curricular affairs at a r and om sample of 62 accredited U.S. medical schools was conducted in 2002 . Results . Fifty-one deans participated ( 82 % response rate ) . Most ( 84 % ) described end-of-life care education as “ very important ” and supported incorporating more end-of-life care teaching into the undergraduate curriculum . Sixty-seven percent reported that insufficient time is currently given to palliative care in their curriculum . Although a majority opposed required courses ( 59 % ) or clerkships ( 70 % ) that focused on end-of-life care , they did unanimously endorse integrating teaching end-of-life care into existing courses or clerkships . Key barriers to incorporating more end-of-life care into the curriculum included lack of time in the curriculum , lack of faculty expertise , and absence of a faculty leader . Conclusion . Associate deans for medical education or curricular affairs in the United States support integrating end-of-life care content into existing courses and clerkships throughout the undergraduate medical curriculum . Successful integration will require institutional investment in faculty development , including both the development of faculty leaders to drive change efforts , and the education of all faculty who teach students and exert influence as role models and mentors . The strong support for end-of-life care education expressed by academic leaders in this study , combined with the high level of interest expressed in the authors ’ 2001 national survey of students , provide evidence of the potential for meaningful change in the undergraduate medical curriculum Aim This study evaluates the impact of an interprofessional home hospice visit ( HHV ) on third-year medical students ’ attitudes toward , and underst and ing of , end-of-life care and the visit 's effect on students ’ views of their emerging professional roles and identities . Methods All third-year medical students at Stony Brook School of Medicine in Stony Brook , New York , USA , participated in an HHV . A didactic session preceded the HHV . Subsequently , students were required to su bmi t a piece of reflective writing detailing the impact of the visit . We conducted a qualitative analysis of a r and om sample drawn from the 467 su bmi tted reflections . Results Six themes emerged from the student reflections : three were related to the students ’ direct observations during the HHV , and three were related to the reflective learning of the students based on their HHV experience . Conclusion The qualitative analysis of the reflective writings showed that the students gained a deep appreciation of the human identity of hospice patients and a humanistic underst and ing of their own role as future physicians The purpose of this study was to assess the impact of an elective geriatric palliative care course on medical students ' attitudes , knowledge , and behaviors regarding communication with terminally ill patients . Surveys were administered at the beginning and end of the elective . Despite a significant increase in knowledge about geriatric and palliative medicine ( F = 24.80 ; P < .001 ) , there were no significant changes in students ' self-reported behaviors when applying curriculum-based communication strategies . However , Output:	Results : There is greater consistency in the content being delivered as part of end-of-life care education within medical schools . The most frequently taught topics include attitudes to death and dying , communication skills , and pain management . Pediatric care and religious/cultural issues are less frequently addressed . Teaching institutions are also utilising a broader range of teaching modalities . Conclusion : There is significant progress in palliative care education within medical schools . Ongoing challenges relate to correlating our current practice in medical education to professional recommendations and the expressed needs of junior doctors to practice competent end-of-life care
MS21935	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In the Sh and ong Intervention Trial , 2 weeks of antibiotic treatment for Helicobacter pylori reduced the prevalence of precancerous gastric lesions , whereas 7.3 years of oral supplementation with garlic extract and oil ( garlic treatment ) or vitamin C , vitamin E , and selenium ( vitamin treatment ) did not . Here we report 14.7-year follow-up for gastric cancer incidence and cause-specific mortality among 3365 r and omly assigned subjects in this masked factorial placebo-controlled trial . Conditional logistic regression was used to estimate the odds of gastric cancer incidence , and the Cox proportional hazards model was used to estimate the relative hazard of cause-specific mortality . All statistical tests were two-sided . Gastric cancer was diagnosed in 3.0 % of subjects who received H pylori treatment and in 4.6 % of those who received placebo ( odds ratio = 0.61 , 95 % confidence interval = 0.38 to 0.96 , P = .032 ) . Gastric cancer deaths occurred among 1.5 % of subjects assigned H pylori treatment and among 2.1 % of those assigned placebo ( hazard ratio [ HR ] of death = 0.67 , 95 % CI = 0.36 to 1.28 ) . Garlic and vitamin treatments were associated with non-statistically significant reductions in gastric cancer incidence and mortality . Vitamin treatment was associated with statistically significantly fewer deaths from gastric or esophageal cancer , a secondary endpoint ( HR = 0.51 , 95 % CI = 0.30 to 0.87 ; P = .014 ) AIM To investigate the effects of Helicobacter pylori ( H pylori ) eradication therapy for treatment of peptic ulcer on the incidence of gastric cancer . METHODS A multicenter prospect i ve cohort study was conducted between November 2000 and December 2007 in Yamagata Prefecture , Japan . The study included patients with H pylori-positive peptic ulcer who decided themselves whether to receive H pylori eradication ( eradication group ) or conventional antacid therapy ( non-eradication group ) . Incidence of gastric cancer in the two groups was determined based on the results of annual endoscopy and question naire surveys , as well as Yamagata Prefectural Cancer Registry data , and was compared between the two groups and by results of H pylori therapy . RESULTS A total of 4133 patients aged between 13 and 91 years ( mean 52.9 years ) were registered , and 56 cases of gastric cancer were identified over a mean follow-up of 5.6 years . The sex- and age-adjusted incidence ratio of gastric cancer in the eradication group , as compared with the non-eradication group , was 0.58 ( 95 % CI : 0.28 - 1.19 ) and ratios by follow-up period ( < 1 year , 1 - 3 years , > 3 years ) were 1.16 ( 0.27 - 5.00 ) , 0.50 ( 0.17 - 1.49 ) , and 0.34 ( 0.09 - 1.28 ) , respectively . Longer follow-up tended to be associated with better prevention of gastric cancer , although not to a significant extent . No significant difference in incidence of gastric cancer was observed between patients with successful eradication therapy ( 32/2451 patients , 1.31 % ) and those with treatment failure ( 11/639 patients , 1.72 % ) . Among patients with duodenal ulcer , which is known to be more prevalent in younger individuals , the incidence of gastric cancer was significantly less in those with successful eradication therapy ( 2/845 patients , 0.24 % ) than in those with treatment failure ( 3/216 patients , 1.39 % ) . CONCLUSION H pylori eradication therapy for peptic ulcer patients with a mean age of 52.9 years at registration did not significantly decrease the incidence of gastric cancer OBJECTIVE --To investigate the association between gastric cancer and prior infection with Helicobacter pylori . DESIGN --Case-control comparison of prevalence of IgG antibodies to H pylori in blood sample s collected prospect ively , before diagnosis of gastric cancer in the cases . Presence of H pylori antibody ( greater than 10 micrograms IgG/ml ) determined by enzyme linked immunosorbent assay ( ELISA ) . SUBJECTS--29 men with a subsequent diagnosis of gastric cancer and 116 aged matched controls selected from over 22,000 middle aged men participating in two ongoing cohort studies ( the British United Provident Association study and the Caerphilly collaborative heart disease study ) , who had provided blood sample s during 1975 - 1982 . RESULTS --20 of the 29 cases ( 69 % ) and 54 of the 116 controls ( 47 % ) were positive for H pylori specific antibody . The median specific IgG concentration was significantly higher in the cases than controls ( 90 micrograms/ml v 3.6 micrograms/ml , p less than 0.01 ) . The estimated odds ratio for the risk of gastric cancer in those with a history of infection with H pylori was 2.77 ( 95 % confidence interval 1.04 to 7.97 , 2p = 0.039 ) . CONCLUSIONS --H pylori infection may be an important cause of gastric cancer ; between 35 % and 55 % of all cases may be associated with such an infection Objective Helicobacter pylori infection and overexpression of cyclo-oxygenase-2 ( COX-2 ) are associated with gastric cancer and its precursors . To evaluate the effect of a selective COX-2 inhibitor alone and combined with H pylori eradication on the evolution of precancerous gastric lesions , a r and omised , placebo-controlled trial was conducted in Linqu County , Sh and ong Province , China . Methods A total of 1024 participants aged 35–64 years with H pylori infection and advanced gastric lesions were r and omly assigned in a factorial design to two interventions or placebo : anti-H pylori treatment for 7 days , and a COX-2 inhibitor ( celecoxib ) for 24 months . The effects of the interventions were evaluated by the regression or progression of advanced gastric lesions . Results Of the 1024 participants who received anti-H pylori treatment or placebo , 919 completed a subsequent 24-month treatment with celecoxib or placebo . The H pylori eradication rate by per- protocol analysis was 78.2 % . Compared with placebo , the proportions of regression of gastric lesions significantly increased in the celecoxib treatment ( 52.8 % vs 41.2 % ) and anti-H pylori treatment ( 59.3 % vs 41.2 % ) group , and OR by per- protocol analysis was 1.72 ( 95 % CI 1.07 to 2.76 ) for celecoxib and 2.19 ( 95 % CI 1.32 to 3.64 ) for H pylori eradication . No statistically significant effect was found for H pylori eradication followed by celecoxib on the regression of advanced gastric lesions ( OR 1.48 , 95 % CI 0.91 to 2.40 ) . Conclusion This population -based intervention trial revealed that celecoxib treatment or H pylori eradication alone had beneficial effects on the regression of advanced gastric lesions . No favourable effects were seen for H pylori eradication followed by celecoxib treatment . Trial registration HARECCTR0500053 in accordance with WHO ICTRP requirements CONTEXT Although chronic Helicobacter pylori infection is associated with gastric cancer , the effect of H pylori treatment on prevention of gastric cancer development in chronic carriers is unknown . OBJECTIVE To determine whether treatment of H pylori infection reduces the incidence of gastric cancer . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , r and omized , placebo-controlled , population -based primary prevention study of 1630 healthy carriers of H pylori infection from Fujian Province , China , recruited in July 1994 and followed up until January 2002 . A total of 988 participants did not have precancerous lesions ( gastric atrophy , intestinal metaplasia , or gastric dysplasia ) on study entry . INTERVENTION Patients were r and omly assigned to receive H pylori eradication treatment : a 2-week course of omeprazole , 20 mg , a combination product of amoxicillin and clavulanate potassium , 750 mg , and metronidazole , 400 mg , all twice daily ( n = 817 ) ; or placebo ( n = 813 ) . MAIN OUTCOME MEASURES The primary outcome measure was incidence of gastric cancer during follow-up , compared between H pylori eradication and placebo groups . The secondary outcome measure was incidence of gastric cancer in patients with or without precancerous lesions , compared between the 2 groups . RESULTS Among the 18 new cases of gastric cancers that developed , no overall reduction was observed in participants who received H pylori eradication treatment ( n = 7 ) compared with those who did not ( n = 11 ) ( P = .33 ) . In a subgroup of patients with no precancerous lesions on presentation , no patient developed gastric cancer during a follow-up of 7.5 years after H pylori eradication treatment compared with those who received placebo ( 0 vs 6 ; P = .02 ) . Smoking ( hazard ratio [ HR ] , 6.2 ; 95 % confidence interval [ CI ] , 2.3 - 16.5 ; P<.001 ) and older age ( HR , 1.10 ; 95 % CI , 1.05 - 1.15 ; P<.001 ) were independent risk factors for the development of gastric cancer in this cohort . CONCLUSIONS We found that the incidence of gastric cancer development at the population level was similar between participants receiving H pylori eradication treatment and those receiving placebo during a period of 7.5 years in a high-risk region of China . In the subgroup of H pylori carriers without precancerous lesions , eradication of H pylori significantly decreased the development of gastric cancer . Further studies to investigate the role of H pylori eradication in participants with precancerous lesions are warranted Background We previously reported that eradication of Helicobacter pylori could reduce the risk of developing gastric cancer in patients with peptic ulcer diseases . In the present study , we further followed up our patient groups to identify factors associated with the development of gastric cancer . Methods Prospect i ve posteradication evaluations were conducted in 1342 consecutive patients ( 1191 men and 151 women ; mean age , 50 years ) with peptic ulcer disease who had received H. pylori eradication therapy . The patients had undergone endoscopic examination before eradication therapy to evaluate peptic ulcers , background gastric mucosa , and H. pylori infection . After confirmation of eradication , follow-up endoscopy was performed yearly . Results A total of 1131 patients were followed for up to 9.5 years ( mean , 3.9 years ) . Gastric cancer developed in 9 of 953 patients cured of infection and in 4 of 178 who had persistent infection ( P = 0.04 ) . The risk of developing gastric cancer after receiving H. pylori eradication therapy was increased according to the grade of baseline gastric mucosal atrophy ( P = 0.01 ) . In patients with peptic ulcer diseases , persistent infection of H. pylori ( hazard ratio , 3.9 ; P = 0.03 ) , the grade of baseline gastric mucosal atrophy ( 3.3 , P = 0.01 ) and age ( 2.0 , P = 0.04 ) were identified as significant risk factors for developing gastric cancer . Conclusions The grade of gastric atrophy was closely related to the development of gastric cancer after receiving H. pylori eradication therapy . Thus , eradication of H. pylori before the significant expansion of atrophy is most beneficial to prevent gastric cancer Among 2258 Helicobacter pylori-seropositive subjects r and omly assigned to receive one-time H. pylori treatment with amoxicillin-omeprazole or its placebo , we evaluated the 15-year effect of treatment on gastric cancer incidence and mortality in subgroups defined by age , baseline gastric histopathology , and post-treatment infection status . We used conditional logistic and Cox regressions for covariable adjustments in incidence and mortality analyses , respectively . Treatment was associated with a statistically significant decrease in gastric cancer incidence ( odds ratio = 0.36 ; 95 % confidence interval [ CI ] = 0.17 to 0.79 ) and mortality ( hazard ratio = 0.26 ; 95 % CI = 0.09 to 0.79 ) at ages 55 years and older and a statistically significant decrease in incidence among those with intestinal metaplasia or dysplasia at baseline ( odds ratio = 0.56 ; 95 % CI = 0.34 to 0.91 ) . Treatment benefits for incidence and mortality among Output:	H. pylori eradication is associated with a significantly lower risk of GC ; this finding has significant implication s for the prevention of this cancer . The benefit is maximized when H. pylori eradication is applied at early stages of the infection
MS21936	*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 Dana-Farber Cancer Institute ( DFCI ) acute lymphoblastic leukemia ( ALL ) Consortium Protocol 91 - 01 was design ed to improve the outcome of children with newly diagnosed ALL while minimizing toxicity . Compared with prior protocol s , post-remission therapy was intensified by substituting dexamethasone for prednisone and prolonging the asparaginase intensification from 20 to 30 weeks . Between 1991 and 1995 , 377 patients ( age , 0 - 18 years ) were enrolled ; 137 patients were considered st and ard risk ( SR ) , and 240 patients were high risk ( HR ) . Following a 5.0-year median follow-up , the estimated 5-year event-free survival ( EFS ) + /- SE for all patients was 83 % + /- 2 % , which is superior to prior DFCI ALL Consortium protocol s conducted between 1981 and 1991 ( P = .03 ) . There was no significant difference in 5-year EFS based upon risk group ( 87 % + /- 3 % for SR and 81 % + /- 3 % for HR , P = .24 ) . Age at diagnosis was a statistically significant prognostic factor ( P = .03 ) , with inferior outcomes observed in infants and children 9 years or older . Patients who tolerated 25 or fewer weeks of asparaginase had a significantly worse outcome than those who received at least 26 weeks of asparaginase ( P < .01 , both univariate and multivariate ) . Older children ( at least 9 years of age ) were significantly more likely to have tolerated 25 or fewer weeks of asparaginase ( P < .01 ) . Treatment on Protocol 91 - 01 significantly improved the outcome of children with ALL , perhaps due to the prolonged asparaginase intensification and /or the use of dexamethasone . The inferior outcome of older children may be due , in part , to increased intolerance of intensive therapy 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 For this study , 118 children with st and ard-risk acute lymphoblastic leukemia ( ALL ) were given r and omized assignments to receive native or pegylated Escherichia coli asparaginase as part of induction and 2 delayed intensification phases . Patients treated with pegaspargase had more rapid clearance of lymphoblasts from day 7 and day 14 bone marrow aspirates and more prolonged asparaginase activity than those treated with native asparaginase . In the first delayed intensification phase , 26 % of native asparaginase patients had high-titer antibodies , whereas 2 % of pegaspargase patients had those levels . High-titer antibodies were associated with low asparaginase activity in the native arm , but not in the pegaspargase arm . Adverse events , infections , and hospitalization were similar between arms . Event-free survival at 3 years was 82 % . A population pharmacodynamic model using the nonlinear mixed effects model ( NONMEM ) program was developed that closely fit the measured enzyme activity and asparagine concentrations . Half-lives of asparaginase were 5.5 days and 26 hours for pegaspargase and native asparaginase , respectively . There was correlation between asparaginase enzymatic activity and depletion of asparagine or glutamine in serum . In cerebrospinal fluid asparagine , depletion was similar with both enzyme preparations . Intensive pegaspargase for newly diagnosed ALL should be tested further in a larger population PURPOSE To improve efficacy and reduce toxicity of treatment for children with acute lymphoblastic leukemia . PATIENTS AND METHODS Patients from all risk groups , including infants and those with T-cell disease , were treated between 1987 and 1991 . St and ard-risk ( SR ) patients did not receive cranial irradiation , whereas high-risk ( HR ) and very high-risk ( VHR ) patients participated in a r and omized comparison of 18 Gy of cranial irradiation conventionally fractionated versus two fractions per day ( hyperfractionated ) . RESULTS At a median follow-up of 9.2 years , the 9-year event-free survival ( EFS + /- SE ) was 75 % + /- 2 % for all 369 patients , 77 % + /- 4 % for the 142 SR patients , and 73 % + /- 3 % for the 227 HR/VHR patients ( P = .37 comparing SR and HR/VHR ) . The CNS , with or without concomitant bone marrow involvement , was the first site of relapse in 19 ( 13 % ) of the 142 SR patients : 16 ( 20 % ) of 79 SR boys and three ( 5 % ) of 63 SR girls . This high incidence of relapses necessitated a recall of SR boys for additional therapy . CNS relapse occurred in only two ( 1 % ) of 227 HR and VHR patients . There were no outcome differences found among r and omized treatment groups . Nine-year overall survival was 84 % + /- 2 % for the entire population , 93 % + /- 2 % for SR children , and 79 % + /- 3 % for HR and VHR children ( P < .01 comparing SR and HR/VHR ) . CONCLUSION A high overall survival outcome was obtained for SR patients despite the high risk of CNS relapse for SR boys , which was presumed to be associated with eliminating cranial radiation without intensifying systemic or intrathecal chemotherapy . For HR/VHR patients , inability to salvage after relapse ( nearly all of which were in the bone marrow ) remains a significant clinical problem Background . L‐asparaginase has been a mainstay of therapy along with vincristine and prednisone in the treatment of acute lymphoblastic leukemia ( ALL ) in children for almost 30 years . Because L‐asparaginase is a foreign protein , the potential exists for severe , dose‐limiting hypersensitivity reactions . To reduce this toxicity , L‐asparaginase has been linked with polyethylene glycol ( PEG ) Background : Administration of L-asparaginase is limited by hypersensitivity reactions mediated by anti-asparaginase antibodies . To overcome this problem , native Escherichia coli L-asparaginase was conjugated to polyethylene glycol ( PEG ) to formulate PEG-L-asparaginase , a preparation with decreased immunogenicity and increased circulating half-life . In early trials , PEG-L-asparaginase was tolerated by patients known to be hypersensitive to the native E. coli product . Methods : The Pediatric Oncology Group conducted a phase II , r and omized trial to compare the efficacy and toxicity of PEG-L-asparaginase compared with native E. coli asparaginase in children with acute lymphoblastic leukemia in second bone marrow relapse . All patients ( n=76 ) received st and ard doses of vincristine and prednisone . Nonhypersensitive patients ( n=34 ) were r and omized to receive either PEG-L-asparaginase of 2500 IU/m2/dose intramuscularly on days 1 and 15 ( treatment I ) or native E. coli asparaginase of 10,000 IU/m2/dose intramuscularly on days 1 , 3 , 5 , 8 , 10 , 12 , 15 , 17 , 19 , 22 , 24 , and 26 ( treatment II ) . Patients with a clinical history of an allergic reaction to unmodified asparaginase were directly assigned to treatment with PEG-L-asparaginase ( n=42 ) . Asparaginase levels and anti-asparaginase antibody titers were monitored in all patients . Response and toxicity were scored using conventional criteria . Results : The complete response rate for the total study population was 41 % . There was no difference in complete response between patients r and omized to PEG ( 47 % ) and native asparaginase ( 41 % ) . PEG was well tolerated even in patients with prior allergic reactions to native asparaginase . PEG half-life was shorter in patients with prior allergy . Conclusions : PEG asparaginase is a useful agent in patients with allergic reactions to native asparaginase The Dana-Farber Cancer Institute ( DFCI ) Childhood ALL Consortium Protocol 95 - 01 was design ed to minimize therapy-related morbidity for children with newly diagnosed ALL without compromising efficacy . Patients participated in r and omized comparisons of ( 1 ) doxorubicin given with or without dexrazoxane , a cardioprotectant ( high-risk patients ) , ( 2 Output:	Evidence is insufficient to assess the effects on health outcomes because of the limited number and power of studies and important flaws in their design or conduct in classifying PEG-asparaginase as a superior drug or not , in the pharmacotherapy of ALL in children and adolescents . PEG-asparaginase can be used as a substitute for native E. coli L-asparaginase , demonstrating similar efficacy and safety .
MS21937	*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 Haemodialysis ( HD ) is associated with the acute loss through the dialysis membrane of biochemical factors either enhancing [ folic acid ( F ) ] or impairing [ asymmetric dimethylarginine ( ADMA ) ] arterial function . Changes in these opposing factors might explain the absence of significant modifications in arterial function during HD . We speculated that intra-HD , instead of pre-HD , F administration would provide beneficial effects on arterial wave reflections and endothelial function by preventing HD-induced F loss . METHODS Arterial wave reflections [ augmentation index ( AIx ) , pulse-wave analysis ] , endothelium-dependent vasodilation ( salbutamol-mediated changes in AIx ) and plasma concentrations of F and ADMA were measured pre-HD and end-HD in 10 patients ( age 67.7 + /- 10.3 years ) . Each subject received F 5 mg either pre-HD or intra-HD in two separate studies 2 - 4 weeks apart , in an open-label r and omized cross-over trial . RESULTS Pre-HD F administration did not prevent significant reductions in F during HD ( end-HD vs. pre-HD , -865 + /- 465 nmol l(-1 ) , P < 0.001 ) , but no significant changes in AIx ( + 1.4 + /- 5.7 % ) or salbutamol-mediated AIx modifications ( + 0.4 + /- 5.5 % ) were observed . By contrast , intra-HD F administration was associated with significant increases in F ( + 298 + /- 283 nmol l(-1 ) , P = 0.010 ) and a significant reduction of AIx ( -4.7 + /- 7.2 % , P = 0.013 ) , but no effects on salbutamol-mediated AIx changes ( + 1.5 + /- 4.4 % ) . There was a trend towards greater HD-induced reductions in plasma ADMA concentrations with intra-HD F administration ( P = 0.066 ) . CONCLUSIONS Intra-HD F administration reduces arterial wave reflections but not endothelial function during HD . Given the prognostic significance of arterial wave reflections in HD patients , the timing of F administration is important in the design of interventional trials in this cohort Background —Increased oxidative stress , elevated plasma homocysteine concentration , increased pulse pressure , and impaired endothelial function constitute risk factors for increased mortality in patients with end-stage renal failure . Methods and Results —We investigated the metabolic and hemodynamic effects of intravenous administration of acetylcysteine , a thiol-containing antioxidant , during a hemodialysis session in a prospect i ve , r and omized , placebo-controlled crossover study in 20 patients with end-stage renal failure . Under control conditions , a hemodialysis session reduced plasma homocysteine concentration to 58±22 % predialysis ( mean±SD ) , whereas in the presence of acetylcysteine , the plasma homocysteine concentration was significantly more reduced to 12±7 % predialysis ( P < 0.01 ) . The reduction of plasma homocysteine concentration was significantly correlated with a reduction of pulse pressure . A 10 % decrease in plasma homocysteine concentration was associated with a decrease of pulse pressure by 2.5 mm Hg . Analysis of the second derivative of photoplethysmogram waveform showed changes of arterial wave reflectance during hemodialysis in the presence of acetylcysteine , indicating improved endothelial function . Conclusions —Acetylcysteine-dependent increase of homocysteine removal during a hemodialysis session improves plasma homocysteine concentration , pulse pressure , and endothelial function in patients with end-stage renal failure BACKGROUND Hyperhomocysteinaemia is a putative risk factor for atherothrombotic cardiovascular disease in the haemodialysis population . High-dose vitamin B therapy does not entirely normalize elevated plasma total homocysteine ( tHcy ) levels in haemodialysis patients . Alternative therapies to reduce tHcy further are therefore required . Modifications of the dialysis regimen may result in a better removal of Hcy . We examined the effect of dialyser membrane pore size on tHcy levels in vitamin-replete chronic haemodialysis patients . METHODS Forty-five haemodialysis patients were dialysed during 4 weeks with a low-flux , a high-flux and a super-flux membrane , in r and om order . Pre-dialysis tHcy was determined at baseline and every 4 weeks . In 18 patients , plasma tHcy before and after dialysis and dialysate tHcy concentrations were measured . RESULTS Pre-dialysis tHcy decreased significantly during 4 weeks super-flux dialysis ( -14.6 + /- 2.8 % ) , whereas it remained stable during high-flux ( + 0.5 + /- 2.4 % ) and low-flux dialysis ( + 1.7 + /- 3.2 % ) . The homocysteine reduction ratio was not different for the three membranes : 0.39 + /- 0.03 for the super-flux , 0.47 + /- 0.02 for the high-flux and 0.39 + /- 0.02 for the low-flux dialyser . The amount of Hcy recovered in the dialysate during a single dialysis session was also similar : 117.5 + /- 3.6 micro mol during super-flux , 95.3 + /- 11.5 micro mol during high-flux and 116.5 + /- 11.6 micro mol during low-flux dialysis . CONCLUSION Super-flux dialysis significantly lowers tHcy in chronic haemodialysis patients . Improved removal of middle-molecule uraemic toxins with inhibitory effects on Hcy-metabolizing enzymes , rather than better dialytic clearance of Hcy itself , may explain the beneficial effect of the super-flux membrane BACKGROUND Patients with chronic kidney disease ( CKD ) have an increased risk of cardiovascular disease ( CVD ) . Preliminary evidence suggests a role for global DNA hypomethylation in the pathogenesis of atherosclerotic complications in CKD . The aims of this study in patients with stage 2 - 4 CKD were ( 1 ) to assess the association between renal function and DNA methylation , ( 2 ) to assess the association between DNA methylation and two markers of atherosclerosis [ common carotid intima-media thickness ( CCA-IMT ) ] and brachial artery endothelium-dependent , flow-mediated dilatation ( BA-FMD ) and ( 3 ) to examine the effect of a multi-step treatment strategy on DNA methylation . METHODS In the Anti-Oxidant Therapy In Chronic Renal Insufficiency study ( ATIC- study ) , 93 patients with stage 2 - 4 CKD were included . In a r and omized , double-blind , placebo-controlled design , the treatment group received pravastatin to which vitamin E was added after 6 months and homocysteine-lowering B-vitamin therapy after another 6 months . DNA methylation was assessed using t and em mass spectrometry . CCA-IMT and BA-FMD were assessed using B-mode ultrasonography . RESULTS At baseline , global DNA methylation was not associated with the estimated glomerular filtration rate ( P = 0.32 ) or with CCA-IMT ( P = 0.62 ) or BA-FMD ( P = 0.51 ) . No effect of the treatment strategy including B-vitamin on global DNA methylation was found either in the total study group or within separate strata of homocysteine concentration and renal function . CONCLUSION In patients with stage 2 - 4 CKD , global DNA methylation is not associated with renal function or with CCA-IMT or BA-FMD . A treatment strategy that includes B-vitamins did not alter global DNA methylation in these patients . These data do not support the role of DNA hypomethylation in CKD-associated vascular disease in patients with stage 2 - 4 CKD The Homocysteine Study ( HOST ) Veterans Affairs Cooperative Studies Program No. 453 , is a prospect i ve , r and omized , two arm , double blind study of patients with end stage renal disease ( ESRD ) or advanced chronic kidney disease ( ACKD , defined as an estimated creatinine clearance of 30 ml/min or less ) . Its primary objective is to determine whether administration of high doses of three vitamins , folic acid , vitamin B6 and vitamin B12 , to lower the high plasma homocysteine levels , will reduce all cause mortality . The secondary objectives are to examine whether the treatment lowers the incidence of myocardial infa rct ion , stroke , amputation of a lower extremity , a composite of death and the foregoing three events , the plasma homocysteine level , and , in ESRD patients undergoing hemodialysis , thrombosis of the vascular access . A unique feature of this trial is that after initial evaluation at enrollment and one return visit the follow up is exclusively by phone ( or , if necessary , by mail ) . The subject is contacted every three months throughout the duration of the study from a central location . The study drug is shipped to the patient from a central location rather supplied locally . In a two year enrollment period , 2006 patients are to be enrolled . The duration of the observation period is four to six years . Data will be stored and analyzed at a coordinating center . The study design has the power to detect a reduction in all cause mortality rate of 17 % . Issues related to the unique features of the design of this study are discussed BACKGROUND Considerable evidence suggests that hyperhomocysteinemia is an independent vascular risk factor that promotes atherosclerosis by inducing endothelial dysfunction . Although folic acid reduces hyperhomocysteinemia , the effect on adverse vascular events is unknown . We hypothesized that in patients with chronic renal failure , a condition associated with both hyperhomocysteinemia and atherosclerosis , treatment with folic acid would improve endothelial function . METHODS AND RESULTS In a prospect i ve , double-blind protocol , 100 patients ( mean age 62 years , 67 men ) with predialysis chronic renal failure were r and omized to 5 mg folic acid or placebo daily for 12 weeks . Endothelial function was assessed by measuring ( 1 ) endothelium-dependent dilation of the brachial artery , ( 2 ) combined serum nitrite/nitrate concentrations , and ( 3 ) plasma von Willebr and factor concentration . Baseline characteristics of the 2 groups were similar . At the end of the study , both serum and red cell folate concentrations were greater in the folic acid group than the placebo group [ mean ( 95 % CI ) 39.0 ( 29.8 to 51.0 ) versus 7.7 ( 6.6 to 8.9 ) microg/L and 739 ( 613 to 891 ) versus 220 ( 184 to 262 ) microg/L , respectively ; both P<0.001 ] . Despite a reduction in hyperhomocysteinemia in the folic acid group compared with the placebo group [ 15.1 ( 14.1 to 16.2 ) versus 20.1 ( 18.2 to 22.2 ) micromol/L ; P<0.001 ] , there were no significant differences in endothelium-dependent dilation , combined serum nitrite/nitrate concentrations , or plasma von Willebr and factor concentration between the 2 groups . CONCLUSIONS High-dose folic acid lowers but fails to normalize hyperhomocysteinemia in patients with predialysis chronic renal failure . This was not accompanied by an improvement of endothelial function and suggests that treatment with folic acid may not reduce the burden of vascular disease in uremia BACKGROUND The hyperhomocysteinemia found in most hemodialysis patients is refractory to combined oral B-vitamin supplementation featuring supraphysiological doses of folic acid ( FA ) . We evaluated whether a high-dose L-folinic acid-based regimen provided improved total homocysteine (tHcy)-lowering efficacy in chronic hemodialysis patients , as suggested by a recent uncontrolled report . METHODS We block-r and omized 48 chronic , stable hemodialysis patients based on their screening predialysis tHcy levels , sex , and dialysis center into two groups of 24 subjects treated for 12 weeks with oral FA at 15 mg/day or an equimolar amount ( 20 mg/day ) of oral L-folinic acid ( FNA ) [ L-5-formyltetrahydrofolate ] . All 48 subjects also received 50 mg/day of oral vitamin B6 and 1.0 mg/day of oral vitamin B12 . RESULTS The mean percentage ( % ) reductions ( with 95 % CIs ) in predialysis tHcy were not significantly different [ FNA = 22.1 % ( 11.8 to 31.4 % ) , FA = 20.7 % ( 11.7 to 30.5 % ) , P = 0.950 by paired t test ] . Final on-treatment values ( mean with 95 % CI ) were as follows : FNA , 15.9 micromol/L ( 14.0 to 18.0 ) ; FA , 16.9 micromol Output:	Homocysteine-lowering therapy had little or no effect on all-cause mortality or any other of this review 's secondary outcomes . Homocysteine-lowering therapies were not found to reduce mortality ( cardiovascular and all-cause ) or cardiovascular events among people with ESKD
MS21938	*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 Inflammation signaled by Janus kinases ( JAKs ) promotes progression of diabetic kidney disease ( DKD ) . Baricitinib is an oral , reversible , selective inhibitor of JAK1 and JAK2 . This study tested the efficacy of baricitinib versus placebo on albuminuria in adults with Type 2 diabetes at high risk for progressive DKD . Methods In this Phase 2 , double-blind , dose-ranging study , participants were r and omized 1:1:1:1:1 to receive placebo or baricitinib ( 0.75 mg daily ; 0.75 mg twice daily ; 1.5 mg daily ; or 4 mg daily ) , for 24 weeks followed by 4–8 weeks of washout . Results Participants ( N = 129 ) were 63±9.1 ( mean±st and ard deviation ) years of age , 27.1 % ( 35/129 ) women and 11.6 % ( 15/129 ) African-American race . Baseline hemoglobin A1c ( HbA1c ) was 7.3±1 % and estimated glomerular filtration rate was 45.0±12.1 mL/min/1.73 m2 with first morning urine albumin – creatinine ratio ( UACR ) of 820 ( 407–1632 ) ( median ; interquartile range ) mg/g . Baricitinib , 4 mg daily , decreased morning UACR by 41 % at Week 24 compared with placebo ( ratio to baseline 0.59 , 95 % confidence interval 0.38–0.93 , P = 0.022 ) . UACR was decreased at Weeks 12 and 24 and after 4–8 weeks of washout . Baricitinib 4 mg decreased inflammatory biomarkers over 24 weeks ( urine C – X – C motif chemokine 10 and urine C – C motif lig and 2 , plasma soluble tumor necrosis factor receptors 1 and 2 , intercellular adhesion molecule 1 and serum amyloid A ) . The only adverse event rate that differed between groups was anemia at 32.0 % ( 8/25 ) for baricitinib 4 mg daily versus 3.7 % ( 1/27 ) for placebo . Conclusions Baricitinib decreased albuminuria in participants with Type 2 diabetes and DKD . Further research is required to determine if baricitinib reduces DKD progression OBJECTIVE Renal dysfunction is a key risk factor for all-cause mortality in patients with type 2 diabetes ( T2D ) . Circulating tumor necrosis factor receptor 1 ( TNFR1 ) was recently suggested as a strong biomarker for end-stage renal failure in T2D . However , its relevance regarding all-cause death has yet to be conclusively established . We aim ed to assess the prognostic value of serum TNFR1 concentration for all-cause death in T2D and diabetic kidney disease ( DKD ) from the SURDIAGENE ( Survie , Diabete de type 2 et Genetique ) study . RESEARCH DESIGN AND METHODS A total of 522 T2D patients with DKD ( estimated glomerular filtration rate [ eGFR ] < 60 and /or urinary albumin-to-creatinine ratio [ uACR ] > 30 mg/mmol ) were followed for a median duration of 48 months , and 196 deaths occurred . RESULTS Incidence rate ( 95 % CI ) for death increased as quartiles of TNFR1 concentration increased ( first quartile : 4.7 % patient-years [ 3.0–6.3 % ] ; second quartile : 7.7 % [ 5.4–10.0 % ] ; third quartile : 9.3 % [ 6.7–11.9 % ] ; fourth quartile : 15.9 % [ 12.2–19.5 % ] ) . In multivariate analysis taking age , diabetes duration , HbA1c , uACR , and eGFR into account , compared with the first quartile , patients from the fourth quartile had an adjusted hazard ratio for death of 2.98 ( 95 % CI 1.70–5.23 ) . The integrated discrimination improvement index was statistically significant when adding TNFR1 concentration to the UK Prospect i ve Diabetes Study outcome equation ( P = 0.031 ) . CONCLUSIONS TNFR1 is a strong prognostic factor for all-cause mortality in T2D with renal dysfunction , and its clinical utility is suggested in addition to established risk factors for all-cause mortality Background We aim ed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)‐α ( TNFR1 and TNFR2 ) and cardiovascular outcomes in patients with stable coronary heart disease . Methods and Results CLARICOR ( Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease ) is a r and omized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease . The primary outcome was a composite of nonfatal acute myocardial infa rct ion , unstable angina pectoris , cerebrovascular disease , and all‐cause mortality . Patients were followed up for 10 years ; discovery sample , those assigned placebo ( 1204 events in n=1998 ) ; and replication sample , those assigned clarithromycin ( 1220 events in n=1979 ) . We used Cox regression adjusted for C‐reactive protein level , established cardiovascular risk factors , kidney function , and cardiovascular drugs . After adjustments , higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample ( hazard ratio per SD increase , 1.13 ; 95 % confidence interval , 1.05–1.22 ; P=0.001 for TNFR1 ; hazard ratio , 1.16 ; 95 % confidence interval , 1.08–1.24 ; P<0.001 for TNFR2 ) . The associations were similar in the replication sample . The associations with the composite outcome were mainly driven by acute myocardial infa rct ion , cardiovascular mortality , and noncardiovascular mortality . The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly ( < 1 % ) . Conclusions Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease . Yet , the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited . Clinical Trial Registration URL : https://www . clinical trials.gov . Unique identifier : NCT00121550 Abstract Cardiovascular disease ( CVD ) is the main public health problem in patients with chronic kidney disease ( CKD ) ; however , there is no established biomarker for predicting CVD morbidity and mortality in CKD . The aim of this study was to evaluate the role of circulating tumor necrosis factor receptors ( cTNFRs ) in predicting CVD risk in CKD patients . We prospect ively recruited 984 patients with CKD from 11 centers between 2006 and 2012 . The levels of cTNFR1 and cTNFR2 were determined by performing an enzyme-linked immunosorbent assay . During the mean follow-up period of 4 years , 36 patients experienced a CVD event . The median serum concentrations of cTNFR1 and cTNFR2 were 2703.4 ( 225.6–13,057.7 ) and 5661.0 ( 634.9–30,599.6 ) pg/mL , respectively , and the cTNFR1 level was closely correlated with the cTNFR2 level ( r = 0.86 , P < .0001 ) . The urinary protein-to-creatinine ratio ( UPCR ) and estimated glomerular filtration rate ( eGFR ) were significantly correlated with the cTNFR2 level ( r = 0.21 for UPCR , r = −0.67 for eGFR ; P < .001 for all ) . Similar correlations were observed for serum cTNFR1 ( r = 0.21 for UPCR , r = −0.75 for eGFR ; P < .001 for all ) . In the Cox proportional hazard analyses , cTNFR1 ( hazard ratio [ HR ] 2.506 , 95 % confidence interval [ CI ] 1.186–5.295 , P = .016 ) and cTNFR2 ( HR 4.156 , 95 % CI 1.913–9.030 , P < .001 ) predicted CVD risk even after adjustment for clinical covariates , such as UPCR , eGFR , and high-sensitivity C-reactive protein . cTNFR1 and 2 are associated with CVD and other risk factors in CKD , independently of eGFR and UPCR . Furthermore , cTNFRs could be relevant predictors of CVD in CKD patients BACKGROUND Several studies have demonstrated that levels of circulating inflammatory markers such as tumour necrosis factorα ( TNFα ) , are associated with early progression of diabetic nephropathy ( DN ) . The aim of this study was to investigate whether there is an association between circulating TNFα receptor and disease progression in patients with advanced type 2 DN and severe proteinuria . METHODS Between 2006 and 2011 , we measured levels of circulating soluble TNFα receptor 1 ( TNFR1 ) and soluble TNFα receptor 2 ( TNFR2 ) at baseline and 4 and 12 months in 101 patients included in a multicenter r and omized controlled trial to compare the effect of optimal doses of renin-angiotensin system blockers in monotherapy or in combination ( dual blockade ) to slow progression of established type 2 DN . The primary composite endpoint was a > 50 % increase in baseline serum creatinine , end-stage renal disease , or death . RESULTS The median follow-up was 32 months ( IQR , 18 - 48 ) , during which time 28 patients ( 22.7 % ) achieved the primary endpoint . The TNFR1 level , but not the TNFR2 level , was correlated with other inflammatory markers . Cox regression analysis showed that the highest TNFR1 levels ( HR , 2.60 ; 95%CI , 1.11 - 86.34 ) and baseline proteinuria ( HR 1.32 ; 95%CI 1.15 - 1.52 ) were associated with the primary endpoint . The mixed model analysis revealed that TNFR1 and the TNFR2 levels did not change after starting treatment with renin-angiotensin system blockers . CONCLUSIONS Our results show that the highest levels of TNFR1 are independently associated with progression of renal disease and death in type 2 DN . The renin angiotensin blockers have no effect on these inflammatory markers Aims /hypothesisMultiplex proteomics could improve underst and ing and risk prediction of major adverse cardiovascular events ( MACE ) in type 2 diabetes . This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes . Methods We combined data from six prospect i ve epidemiological studies of 30–77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay . Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE . We used gradient-boosted machine learning and lasso regularised Cox regression in a r and om 75 % training sub sample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25 % test sub sample . Results Of 1211 adults with type 2 diabetes ( 32 % women ) , 211 experienced a MACE over a mean ( ±SD ) of 6.4 ± 2.3 years . We replicated associations ( < 5 % false discovery rate ) between risk of MACE and eight proteins : matrix metalloproteinase (MMP)-12 , IL-27 subunit α ( IL-27a ) , kidney injury molecule (KIM)-1 , fibroblast growth factor (FGF)-23 , protein S100-A12 , TNF receptor (TNFR)-1 , TNFR-2 and TNF-related apoptosis-inducing lig and receptor (TRAIL-R)2 . Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 ( 95 % CI 0.682 , 0.689 ) to 0.748 ( 95 % CI 0.746 , 0.751 ) . A sparse model of 20 added proteins achieved a C statistic of 0.747 ( 95 % CI 0.653 , 0.842 ) in the test sample . Conclusions /interpretationWe identified eight protein biomarkers , four of which are novel , for risk of MACE in community residents with type 2 diabetes , and found improved risk prediction by combining multiplex proteomics with an Output:	The subgroup analyses and sensitivity analyses further illustrated these results of renal outcome and its robustness . Circulating TNFR-1 and TNFR-2 are independently associated with higher risk of renal disease progression , CVD events , and mortality in patients with diabetes and might contribute to the clinical risk assessment in the future
MS21939	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In a cluster r and omized trial , Kojo Yeboah-Antwi and colleagues find that integrated management of malaria and pneumonia in children under five by community health workers is both feasible and effective Background Human re source limitations are a challenge to the delivery of antiretroviral therapy ( ART ) in low-re source setting s. We conducted a cluster r and omized trial to assess the effect of community-based peer health workers ( PHW ) on AIDS care of adults in Rakai , Ug and a. Methodology /Principal Findings 15 AIDS clinics were r and omized 2∶1 to receive the PHW intervention ( n = 10 ) or control ( n = 5 ) . PHW tasks included clinic and home-based provision of counseling , clinical , adherence to ART , and social support . Primary outcomes were adherence and cumulative risk of virologic failure ( > 400 copies/mL ) . Secondary outcomes were virologic failure at each 24 week time point up to 192 weeks of ART . Analysis was by intention to treat . From May 2006 to July 2008 , 1336 patients were followed . 444 ( 33 % ) of these patients were already on ART at the start of the study . No significant differences were found in lack of adherence ( < 95 % pill count adherence risk ratio [ RR ] 0.55 , 95 % confidence interval [ CI ] 0.23–1.35 ; < 100 % adherence RR 1.10 , 95 % CI 0.94–1.30 ) , cumulative risk of virologic failure ( RR 0.81 , 95 % CI 0.61–1.08 ) or in shorter-term virologic outcomes ( 24 week virologic failure RR 0.93 , 95 % CI 0.65–1.32 ; 48 week , RR 0.83 , 95 % CI 0.47–1.48 ; 72 week , RR 0.81 , 95 % CI 0.44–1.49 ) . However , virologic failure rates ≥96 weeks into ART were significantly decreased in the intervention arm compared to the control arm ( 96 week failure RR 0.50 , 95 % CI 0.31–0.81 ; 120 week , RR 0.59 , 95 % CI 0.22–1.60 ; 144 week , RR 0.39 , 95 % CI 0.16–0.95 ; 168 week , RR 0.30 , 95 % CI 0.097–0.92 ; 192 week , RR 0.067 , 95 % CI 0.0065–0.71 ) . Conclusions / Significance A PHW intervention was associated with decreased virologic failure rates occurring 96 weeks and longer into ART , but did not affect cumulative risk of virologic failure , adherence measures , or shorter-term virologic outcomes . PHWs may be an effective intervention to sustain long-term ART in low-re source setting s. Trial Registration Clinical Trials.gov BACKGROUND African American ( AA ) women with Type 2 diabetes mellitus ( T2DM ) in the rural south experience less weight loss and poorer glycemic control in traditional diabetes management programs compared to Caucasians . This paper describes the design , rationale , and baseline characteristics from an innovative community health worker ( CHW ) delivered intervention program in this population . METHODS / DESIGN This prospect i ve trial r and omized rural AA women with uncontrolled T2DM ( HbA1c ≥ 7.0 ) to receive a behaviorally-centered , culturally-tailored lifestyle intervention during 16 contacts from a trained AA CHW or 16 approved diabetes educational mailings . Changes from baseline in glycosylated hemoglobin levels ( HbA1c ) , blood pressure ( BP ) , weight , body mass index ( BMI ) , self-reported dietary and physical activity patterns , and psychosocial measures including diabetes distress , empowerment , depression , self-care , medication adherence , and life satisfaction will be assessed at 6- and 12-months . BASELINE RESULTS Two hundred AA women ( mean age = 53.09 ± 10.89 years ) with T2DM from impoverished rural communities were enrolled . Baseline data demonstrated profoundly uncontrolled diabetes of long term duration ( mean HbA1c = 9.11 ± 1.82 ; mean BMI = 37.68 ± 8.20 ; mean BP = 134.51 ± 20.39/84.19 ± 11.68 ; 10.5 ± 0.7 years ) . Self-care behavior assessment revealed poor dietary and medication adherence and sedentary lifestyle . Most psychosocial measures ranged within normal limits . CONCLUSION The present sample of AA women from impoverished rural communities exhibited significantly uncontrolled T2DM of long duration with associated obesity and poor lifestyle behaviors . An innovative CHW led lifestyle intervention may lead to more effective strategies for T2DM management in this population OBJECTIVE Latinos with type 2 diabetes ( T2D ) face major healthcare access and disease management disparities . We examined the impact of the Diabetes Among Latinos Best Practice s Trial ( DIALBEST ) , a community health worker (CHW)–led structured intervention for improving glycemic control among Latinos with T2D . RESEARCH DESIGN AND METHODS A total of 211 adult Latinos with poorly controlled T2D were r and omly assigned to a st and ard of healthcare ( n = 106 ) or CHW ( n = 105 ) group . The CHW intervention comprised 17 individual sessions delivered at home by CHWs over a 12-month period . Sessions addressed T2D complications , healthy lifestyles , nutrition , healthy food choices and diet for diabetes , blood glucose self-monitoring , and medication adherence . Demographic , socioeconomic , lifestyle , anthropometric , and biomarker ( HbA1c , fasting blood glucose , and lipid profile ) data were collected at baseline and 3 , 6 , 12 , and 18 months ( 6 months postintervention ) . Groups were equivalent at baseline . RESULTS Participants had high HbA1c at baseline ( mean 9.58 % [ 81.2 mmol/mol ] ) . Relative to participants in the control group , CHWs had a positive impact on net HbA1c improvements at 3 months ( −0.42 % [ −4.62 mmol/mol ] ) , 6 months ( −0.47 % [ −5.10 mmol/mol ] ) , 12 months ( −0.57 % [ −6.18 mmol/mol ] ) , and 18 months ( −0.55 % [ −6.01 mmol/mol ] ) . The overall repeated- measures group effect was statistically significant ( mean difference −0.51 % [ −5.57 mmol/mol ] , 95 % CI −0.83 , −0.19 % [ −9.11 , −2.03 mmol/mol ] , P = 0.002 ) . CHWs had an overall significant effect on fasting glucose concentration that was more pronounced at the 12- and 18-month visits . There was no significant effect on blood lipid levels , hypertension , and weight . CONCLUSIONS DIALBEST is an effective intervention for improving blood glucose control among Latinos with T2D Background Early diagnosis and prompt , effective treatment of uncomplicated malaria is critical to prevent severe disease , death and malaria transmission . We assessed the impact of rapid malaria diagnostic tests ( RDTs ) by community health workers ( CHWs ) on provision of artemisinin-based combination therapy ( ACT ) and health outcome in fever patients . Methodology /Principal Findings Twenty-two CHWs from five villages in Kibaha District , a high-malaria transmission area in Coast Region , Tanzania , were trained to manage uncomplicated malaria using RDT aided diagnosis or clinical diagnosis ( CD ) only . Each CHW was r and omly assigned to use either RDT or CD the first week and thereafter alternating weekly . Primary outcome was provision of ACT and main secondary outcomes were referral rates and health status by days 3 and 7 . The CHWs enrolled 2930 fever patients during five months of whom 1988 ( 67.8 % ) presented within 24 hours of fever onset . ACT was provided to 775 of 1457 ( 53.2 % ) patients during RDT weeks and to 1422 of 1473 ( 96.5 % ) patients during CD weeks ( Odds Ratio ( OR ) 0.039 , 95 % CI 0.029–0.053 ) . The CHWs adhered to the RDT results in 1411 of 1457 ( 96.8 % , 95 % CI 95.8–97.6 ) patients . More patients were referred on inclusion day during RDT weeks ( 10.0 % ) compared to CD weeks ( 1.6 % ) . Referral during days 1–7 and perceived non-recovery on days 3 and 7 were also more common after RDT aided diagnosis . However , no fatal or severe malaria occurred among 682 patients in the RDT group who were not treated with ACT , supporting the safety of withholding ACT to RDT negative patients . Conclusions / Significance RDTs in the h and s of CHWs may safely improve early and well-targeted ACT treatment in malaria patients at community level in Africa . Trial registration Clinical Trials.gov OBJECTIVES We tested the effectiveness of a culturally tailored , behavioral theory-based community health worker intervention for improving glycemic control . METHODS We used a r and omized , 6-month delayed control group design among 164 African American and Latino adult participants recruited from 2 health systems in Detroit , Michigan . Our study was guided by the principles of community-based participatory research . Hemoglobin A1c ( HbA1c ) level was the primary outcome measure . Using an empowerment-based approach , community health workers provided participants with diabetes self-management education and regular home visits , and accompanied them to a clinic visit during the 6-month intervention period . RESULTS Participants in the intervention group had a mean HbA1c value of 8.6 % at baseline , which improved to a value of 7.8 % at 6 months , for an adjusted change of -0.8 percentage points ( P < .01 ) . There was no change in mean HbA1c among the control group ( 8.5 % ) . Intervention participants also had significantly greater improvements in self-reported diabetes underst and ing compared with the control group . CONCLUSIONS This study contributes to the growing evidence for the effectiveness of community health workers and their role in multidisciplinary teams engaged in culturally appropriate health care delivery OBJECTIVE The Northern Manhattan Diabetes Community Outreach Project evaluated whether a community health worker ( CHW ) intervention improved clinical ly relevant markers of diabetes care in adult Hispanics . RESEARCH DESIGN AND METHODS Participants were adult Hispanics , ages 35–70 years , with recent hemoglobin A1c ( A1C ) ≥8 % ( ≥64 mmol/mol ) , from a university-affiliated network of primary care practice s in northern Manhattan ( New York City , NY ) . They were r and omized to a 12-month CHW intervention ( n = 181 ) , or enhanced usual care ( educational material s mailed at 4-month intervals , preceded by phone calls , n = 179 ) . The primary outcome was A1C at 12 months ; the secondary outcomes were systolic blood pressure ( SBP ) , diastolic blood pressure , and LDL-cholesterol levels . RESULTS There was a nonsignificant trend toward improvement in A1C levels in the intervention group ( from unadjusted mean A1C of 8.77 to 8.40 % ) , as compared with usual care ( from 8.58 to 8.53 % ) ( P = 0.131 ) . There was also a nonsignificant trend toward an increase in SBP and LDL cholesterol in the intervention arm . Intervention fidelity , measured as the number of contacts in the intervention arm ( visits , phone contacts , group support , and nutritional education ) , showed a borderline association with greater A1C reduction ( P = 0.054 ) . When assessed separately , phone contacts were associated with greater A1C reduction ( P = 0.04 ) . CONCLUSIONS The trend toward A1C reduction with the CHW intervention failed to achieve statistical significance . Greater intervention fidelity may achieve better glycemic control , and more accessible treatment models , such as phone-based interventions , may be more efficacious in socioeconomically disadvantaged population Abstract Objectives : To assess the quality and safety of having community health workers ( CHWs ) in rural Zambia use rapid diagnostic tests ( RDTs ) and provide integrated management of malaria and pneumonia . Design / methods : In the context of a cluster-r and omized controlled trial of two models for community-based management of malaria and /or non-severe pneumonia in children under 5 years old , CHWs in the intervention arm were trained to use RDTs , follow a simple algorithm for classification and treat malaria with artemether – lumefantrine ( AL ) and pneumonia with amoxicillin . CHW records were review ed to assess the ability of the CHWs to appropriately classify and treat malaria Output:	Improvements were observed in perceptions of health , quality of life , knowledge , self-efficacy , self-management , and caregiver support . Nurses and CHWs play a pivotal role in community-based care . Evidence suggests community-based interventions facilitate the necessary support for stroke survivors , caregivers , families , and communities to optimize stroke recovery .
MS21940	*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 objective of this study was to determine whether a generalizable best- practice individualized behavioral intervention reduced BMI z score relative to st and ard dietetic care among overweight children . METHODS . The design consisted of an assessor-blinded , r and omized , controlled trial involving 134 overweight children ( 59 boys , 75 girls ; BMI ≥ 98th centile relative to United Kingdom 1990 reference data for children aged 5–11 years ) who were r and omly assigned to a best- practice behavioral program ( intervention ) or st and ard care ( control ) . The intervention used family-centered counseling and behavioral strategies to modify diet , physical activity , and sedentary behavior . BMI z score , weight , objective ly measured physical activity and sedentary behavior , fat distribution , quality of life , and height z score were recorded at baseline and at 6 and 12 months . RESULTS . The intervention had no significant effect relative to st and ard care on BMI z score from baseline to 6 months and 12 months . BMI z score decreased significantly in both groups from baseline to 6 and 12 months . For those who complied with treatment , there was a significantly smaller weight increase in those in the intervention group compared with control subjects from baseline to 6 months . There were significant between-group differences in favor of the intervention for changes in total physical activity , percentage of time spent in sedentary behavior , and light-intensity physical activity . CONCLUSIONS . A generalizable , best- practice individualized behavioral intervention had modest benefits on objective ly measured physical activity and sedentary behavior but no significant effect on BMI z score compared with st and ard care among overweight children . The modest magnitude of the benefits observed perhaps argues for a longer-term and more intense intervention , although such treatments may not be realistic for many health care systems OBJECTIVE : To evaluate the effectiveness of active parental involvement in a lifestyle intervention for the management of childhood obesity . DESIGN : Forty-two overweight children ( 32 girls and 10 boys ) , aged 9.2±0.2 years and with percent overweight 39.8±2.7 % , were r and omly allocated either to a child- and -parent group ( N = 23 ) or a child-alone group ( N = 19 ) . Both groups attended a 3-month multidisciplinary program extended by booster sessions during follow-up , which involved many cognitive behavioral therapy principles and assigned high self-regulation to the children , but differed in parental involvement . Percent overweight was evaluated at baseline , and at 3 , 6 , and 18 months thereafter . RESULTS : There was no significant interaction between time and group or a significant difference between groups . Percent overweight decreased by 4.9±1.4 at 18 months ( p < 0.001 ) ; the reduction occurred during the active phase of the treatment ( 0 - 3 months ) and was maintained thereafter . CONCLUSION : In the setting of the present study , the active parental involvement did not significantly modify the results of lifestyle interventions for children ’s overweight management Background Developing effective prevention and intervention programs for the formative preschool years is seen as an essential step in combating the obesity epidemic across the lifespan . The overall goal of the current project is to measure the effectiveness of a healthy eating and childhood obesity prevention intervention , the MEND ( Mind Exercise Nutrition Do It ! ) program that is delivered to parents of children aged 2 - 4 years . Methods / Design This r and omised controlled trial will be conducted with 200 parents and their 2 - 4 year old children who attend the MEND 2 - 4 program in metropolitan and regional Victoria . Parent-child dyads will attend ten 90-minute group workshops . These workshops focus on general nutrition , as well as physical activity and behaviours . They are typically held at community or maternal and child health centres and run by a MEND 2 - 4 trained program leader . Child eating habits , physical activity levels and parental behaviours and cognitions pertaining to nutrition and physical activity will be assessed at baseline , the end of the intervention , and at 6 and 12 months post the intervention . Informed consent will be obtained from all parents , who will then be r and omly allocated to the intervention or wait-list control group . Discussion Our study is the first RCT of a healthy eating and childhood obesity prevention intervention targeted specifically to Australian parents and their preschool children aged 2 - 4 years . It responds to the call by experts in the area of childhood obesity and child health that prevention of overweight in the formative preschool years should focus on parents , given that parental beliefs , attitudes , perceptions and behaviours appear to impact significantly on the development of early overweight . This is ' solution-oriented ' rather than ' problem-oriented ' research , with its focus being on prevention rather than intervention . If this is a positive trial , the MEND2 - 4 program can be implemented as a national program . Trial Registration Australian New Zeal and Clinical Trials Registry To decrease BMI in overweight and obese children , improved dietary intake and increased physical activity are key elements . Our objective was to evaluate the impact of a 1-y food and physical activity intervention on energy and macronutrient intake in overweight and obese children . A r and omized open trial was conducted with 92 overweight or obese 10.4 ± 1.08-y-old children . The intervention included 14 group sessions with different themes regarding food and physical activity . Dietary intake was assessed with diet history interviews covering 14 d at baseline and 4-d food records after 1 y and was evaluated according to national dietary recommendations . The control group participated in the same measurements as the intervention group but did not take part in group sessions . After 1 y , both groups had decreased their energy intake ( EI ) relative to total energy expenditure , but the effect was more pronounced for the intervention group than for the control group . At 1 y follow-up , a larger proportion of children in the intervention group compared with the control group met the recommended intake of refined sugar ( P = 0.019 ) . However , the groups did not differ in the proportion children who met the recommended intake of dietary fiber . Further , SFA intake relative to total EI did not differ between the groups at 1 y follow-up . In conclusion , despite a rather comprehensive intervention , only modest effects were achieved with respect to reduced EI and improved macronutrient intake 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 . Abstract Objective To identify risk factors in early life ( up to 3 years of age ) for obesity in children in the United Kingdom . Design Prospect i ve cohort study . Setting Avon longitudinal study of parents and children , United Kingdom . Participants 8234 children in cohort aged 7 years and a sub sample of 909 children ( children in focus ) with data on additional early growth related risk factors for obesity . Main outcome measures Obesity at age 7 years , defined as a body mass index 3 95th centile relative to reference data for the UK population in 1990 . Results Eight of 25 putative risk factors were associated with a risk of obesity in the final models : parental obesity ( both parents : adjusted odds ratio , 10.44 , 95 % confidence interval 5.11 to 21.32 ) , very early ( by 43 months ) body mass index or adiposity rebound ( 15.00 , 5.32 to 42.30 ) , more than eight hours spent watching television per week at age 3 years ( 1.55 , 1.13 to 2.12 ) , catch-up growth ( 2.60 , 1.09 to 6.16 ) , st and ard deviation score for weight at age 8 months ( 3.13 , 1.43 to 6.85 ) and 18 months ( 2.65 , 1.25 to 5.59 ) ; weight gain in first year ( 1.06 , 1.02 to 1.10 per 100 g increase ) ; birth weight , per 100 g ( 1.05 , 1.03 to 1.07 ) ; and short ( < 10.5 hours ) sleep duration at age 3 years ( 1.45 , 1.10 to 1.89 ) . Conclusion Eight factors in early life are associated with an increased risk of obesity in childhood Objective : The aim of the study was to compare the efficacy of group treatment stressing a health-promoting lifestyle with routine counseling in the treatment of childhood obesity . Design and subjects : Seventy obese children ( weight for height 115–182 % ) aged 7–9 years were r and omized either to routine counseling ( two appointments for children ) or to family-based group treatment ( 15 separate sessions for parents and children ) . These sessions included nutrition education , physical activity education and behavioral therapy . Outcome measures : Children 's weights and heights were measured at baseline , after the 6-month intervention and after the 6-month follow-up . The change of weight for height based on Finnish growth charts was used as the primary , and changes in body mass index ( BMI ) and BMI st and ard deviation scores ( BMI -SDS ) as secondary outcome measures . Results : Children attending the group treatment lost more weight for height ( 6.8 % ) than children receiving routine counseling ( 1.8 % ) ( P=0.001 ) . The difference was significant when the data were analyzed in four groups by the cut-off limits of 0 , −5 and −10 % for the change in weight for height . The respective decreases in BMI were 0.8 vs 0.0 ( P=0.003 ) and in BMI -SDS 0.3 vs 0.2 ( P=0.022 ) . The results remained similar in adjusted analyses . Both group and routine programs were feasible with a high , 87–99 % , participation rate in sessions and appointments and very low , 3 % or less , attrition rate from the programs . Six months after the intervention , beneficial effects were partly lost , but for changes in weight for height and BMI , the differences between the two treatment programs still were significant , and for BMI -SDS , there was a trend . Conclusions : Family-based group treatment that stresses a health-promoting lifestyle and is given separately for parents and children , offers an effective mode of therapy to treat obese school-aged children The effectiveness of a health and nutrition education programme , in changing certain chronic disease risk factors , was assessed after the 6 years intervention period was completed . The school-based intervention programme was applied to all children registered in the first grade ( age 5.5 - 6.5 years ) in 1992 in two counties of Crete , while the children from a third county served as a control group . In order to assess the effectiveness of the intervention , a variety of biological and behavioural parameters were measured before and following completion of the intervention in a r and omly selected school-based sample of 602 intervention group ( IG ) and 444 control group ( CG ) pupils . At the end of the 6-year period , it was found that biochemical indices generally improved significantly more in the IG compared with the CG ( mean change for IG v. CG was -0.27 v. -0.12 mmol/l for total cholesterol ( TC ) ; -0.07 v. + 0.24 for TC : HDL and -0.13 v. + 0.14 for LDL : HDL ) . Similarly , the changes observed in the anthropometric variables in the two groups were in favour of the IG ( + 3.68 v. + 4.28 kg/m2 for BMI ; + 2.97 v. + 4.47 mm for biceps skinfold ) . Total energy intake and consumption of total fat and saturated fat increased significantly less in the IG compared with the CG ( + 747.7 v. 1534.7 kJ ( + 178.7 v. + 366.8 kcal ) ; + 5.9 v. + 18.8 g and + 0.8 v. + 5.1 g respectively ) , while time devoted to leisure time physical activity and cardiovascular run test performance increased significantly more in the IG ( + 281 v. + 174 min/week and + 2.5 v. + 1.2 stages respectively ) . The findings of the present study underline the importance of such programmes in health promotion and disease prevention . Although the long-term effects of these programmes can only be assessed by tracking this population through to adolescence and adulthood , these programmes seem to have the potential to lead to a healthier lifestyle and thus a reduction in risk factor levels BACKGROUND & AIMS To assess the effects of a low cost behavioral prevention program in a preschool setting . METHODS 64 Kindergartens in 4 Bavarian regions were r and omly assigned as intervention or controls in a 2:1 ratio . Sample s of 1318 and 1340 children examined in the school entrance health examination at 5.7+/-2.6 and 17.6+/-2.3 months ( mean+/-st and ard deviation for first and second sample ) after the start of the program were analysed . MEASUREMENTS Main outcome measures were the prevalence of high fruit and vegetable consumption , low consumption of high caloric drinks assessed in parental question naires , overweight and obesity , and secondary , further dietary habits and results of motoric testing . RESULTS The program led to an increased proportion of children with high fruit and vegetable consumption already after 6 months , which was sustainable with adjusted odds ratios of 1.59 ( 1.26 : 2.01 ) and 1.48 ( 1.0 Output:	In effective long-term treatment studies , medium and high intensity parental involvement were identified most frequently ; whereas in prevention studies low intensity parental involvement was identified most frequently . Parenting skills , generic and specific to lifestyle behaviour , scored frequently in effective weight control interventions . We conclude that intensity of parental involvement and behaviour change techniques are important issues in the effectiveness of long-term childhood weight control interventions
MS21941	*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 Foot musculoskeletal deficits are seldom addressed by preventive medicine despite their high prevalence in patients with diabetic polyneuropathy . AIM : To investigate the effects of strengthening , stretching , and functional training on foot rollover process during gait . Methods A two-arm parallel-group r and omized controlled trial with a blinded assessor was design ed . Fifty-five patients diagnosed with diabetic polyneuropathy , 45 to 65 years-old were recruited . Exercises for foot-ankle and gait training were administered twice a week , for 12 weeks , to 26 patients assigned to the intervention group , while 29 patients assigned to control group received recommended st and ard medical care : pharmacological treatment for diabetes and foot care instructions . Both groups were assessed after 12 weeks , and the intervention group at follow-up ( 24 weeks ) . Primary outcomes involved foot rollover changes during gait , including peak pressure ( PP ) . Secondary outcomes involved time-to-peak pressure ( TPP ) and pressure – time integral ( PTI ) in six foot- areas , mean center of pressure ( COP ) velocity , ankle kinematics and kinetics in the sagittal plane , intrinsic and extrinsic muscle function , and functional tests of foot and ankle . Results Even though the intervention group primary outcome ( PP ) showed a not statistically significant change under the six foot areas , intention-to-treat comparisons yielded softening of heel strike ( delayed heel TPP , p=.03 ) , better eccentric control of forefoot contact ( decrease in ankle extensor moment , p<.01 ; increase in function of ankle dorsiflexion , p<.05 ) , earlier lateral forefoot contact with respect to medial forefoot ( TPP anticipation , p<.01 ) , and increased participation of hallux ( increased PP and PTI , p=.03 ) and toes ( increase in PTI , medium effect size ) . A slower COP mean velocity ( p=.05 ) , and an increase in overall foot and ankle function ( p<.05 ) were also observed . In most cases , the values returned to baseline after the follow-up ( p<.05 ) . Conclusions Intervention discreetly changed foot rollover towards a more physiological process , supported by improved plantar pressure distribution and better functional condition of the foot ankle complex . Continuous monitoring of the foot status and patient education are necessary , and can contribute to preserving the integrity of foot muscles and joints impaired by polyneuropathy . Trial registration Clinical Trials.gov Identifier : NCT01207284 , registered in 20th September 2010 PURPOSE To evaluate the effectiveness of home temperature monitoring to reduce the incidence of foot ulcers in high-risk patients with diabetes . METHODS In this physician-blinded , 18-month r and omized controlled trial , 225 subjects with diabetes at high risk for ulceration were assigned to st and ard therapy ( St and ard Therapy Group ) or dermal thermometry ( Dermal Thermometry Group ) groups . Both groups received therapeutic footwear , diabetic foot education , regular foot care , and performed a structured foot inspection daily . Dermal Thermometry Group subjects used an infrared skin thermometer to measure temperatures on 6 foot sites twice daily . Temperature differences > 4 degrees F between left and right corresponding sites triggered patients to contact the study nurse and reduce activity until temperatures normalized . RESULTS A total of 8.4 % ( n=19 ) subjects ulcerated over the study period . Subjects were one third as likely to ulcerate in the Dermal Thermometry Group compared with the St and ard Therapy Group ( 12.2 % vs 4.7 % , odds ratio 3.0 , 95 % confidence interval , 1.0 to 8.5 , P=.038 ) . Proportional hazards regression analysis suggested that thermometry intervention was associated with a significantly longer time to ulceration ( P=.04 ) , adjusted for elevated foot ulcer classification ( International Working Group Risk Factor 3 ) , age , and minority status . Patients that ulcerated had a temperature difference that was 4.8 times greater at the site of ulceration in the week before ulceration than did a r and om 7 consecutive-day sample of 50 other subjects that did not ulcerate ( 3.50+/-1.0 vs 0.74+/-0.05 , P=.001 ) . CONCLUSIONS High temperature gradients between feet may predict the onset of neuropathic ulceration and self-monitoring may reduce the risk of ulceration BACKGROUND Neuropathic foot ulcers are among the major health problems faced by patients with diabetes mellitus . OBJECTIVE To evaluate the preventive efficacy of a therapeutic education and protective footwear program in the incidence and recurrence of neuropathic ulcers due to diabetes . METHODS Fifty-three patients with diabetes and neuropathy from a public healthcare unit in Porto Alegre , Rio Gr and e do Sul , took part in a clinical trial for two years . The participants were r and omly allocated to an intervention group ( n=30 ) or a control group ( n=23 ) . Therapeutic education was provided in group sessions , and protective footwear was supplied in accordance with individual prescriptions . The nonparametric Mann-Whitney test was used to determine differences in incidence and recurrence of ulceration between the groups . Life-table analysis and the Kaplan-Meier method were used to measure the duration of ulcer-free survival . RESULTS In the intervention group , the ulcer incidence rate was 38.1 % compared to 51.1 % in the control group . Among the participants who presented ulcers , 83 % were in the control group and 16.7 % in the intervention group . After one year , the participants in the intervention group had a 75 % chance of being ulcer-free , compared with 61 % in the control group , and these percentages reduced to 60 % and 52 % respectively after two years . There was a tendency toward shorter survival among the control group participants . CONCLUSION Although the proposed program lowered recurrence rates and increased the duration of ulcer-free survival , it was unable to prevent occurrence and recurrence of neuropathic ulcers due to diabetes Abstract Aims /hypothesisThis observer-blind , r and omised controlled trial was design ed to determine the effect of a foot care education programme in the secondary prevention of foot ulcers . Methods People with newly healed foot ulcers attending one of three specialist clinics were allocated to receive either targeted , one-to-one education or usual care , using a computer-generated r and om allocation sequence that had been prepared in advance but which was concealed from the clinical research er . The primary outcome was ulcer incidence at 12 months . Secondary outcomes were ulcer incidence at 6 months and incidence of amputation , mood ( Hospital Anxiety and Depression Scale ) and quality of life ( Diabetic Foot Ulcer Scale ) at 6 and 12 months . Protective foot care behaviours ( Nottingham Assessment of Functional Footcare ) were assessed at 12 months . Results There were 87 ( mean [ SD ] age 63.5 [ 12.1 ] years ) patients in the intervention group and 85 control patients ( mean [ SD ] age 64.9 [ 10.9 ] years ) . The groups were comparable at baseline . No significant differences ( p > 0.05 ) were observed between groups in ulcer incidence at either 6 months ( intervention 30 % , control 21 % ) or 12 months ( intervention 41 % , control 41 % ) . Recommended foot care behaviours at 12 months were better in the intervention than in the control group ( p = 0.03 ) , but education had no significant ( p > 0.05 ) effect on mood , quality of life or amputations . Conclusions /interpretationEven though the intervention was associated with improved foot care behaviour , there was no evidence that this programme of targeted education was associated with clinical benefit in this population when compared with usual care . The usefulness and optimal delivery of education to such a high-risk group requires further evaluation . Trial registration : Clinical Trials.gov NCT00729456 Funding : Diabetes UK project grant BACKGROUND We aim ed to investigate whether a home exercise for self-care program that consists of range of motion ( ROM ) , stretching , and strengthening exercises could improve ROM for foot joints and plantar pressure distribution during walking in diabetic patients to prevent diabetic foot complications . METHODS Seventy-six diabetic patients were recruited ( 38 with neuropathy and 38 without neuropathy ) . Neuropathy and nonneuropathy groups were r and omly divided into a home exercise group ( n = 19 ) and a control group ( n = 19 ) . Exercise groups performed their own respective training programs for 4 weeks , whereas no training was done in the control group . Total contact area and plantar pressure under six foot areas before and after the exercise program were measured . Ankle and first metatarsophalangeal joint ROM were measured before and after the exercise program . RESULTS In the exercise group , there were significant improvements in ROM for the ankle and first metatarsophalangeal joints ( P < .001 ) ; static pedobarographic values showed significant reduction in right forefoot-medial pressure ( P = .010 ) ; and significant decreases were seen in dynamic pedobarographic values of peak plantar pressure at the left forefoot medial ( P = .007 ) , right forefoot lateral ( P = .018 ) , left midfoot ( P < .001 ) , and right hindfoot ( P = .021 ) after exercise . No significant positive or negative correlation was found between the neuropathy and nonneuropathy groups ( P > .05 ) . CONCLUSIONS A home exercise program could be an effective preventive method for improving ROM for foot joints and plantar pressure distribution in diabetic patients independent of the presence of neuropathy Diabetic foot ulceration poses a heavy burden on the patient and the healthcare system , but prevention thereof receives little attention . For every euro spent on ulcer prevention , ten are spent on ulcer healing , and for every r and omized controlled trial conducted on prevention , ten are conducted on healing . In this article , we argue that a shift in priorities is needed . For the prevention of a first foot ulcer , we need more insight into the effect of interventions and practice s already applied globally in many setting s. This requires systematic recording of interventions and outcomes , and well- design ed r and omized controlled trials that include analysis of cost-effectiveness . After healing of a foot ulcer , the risk of recurrence is high . For the prevention of a recurrent foot ulcer , home monitoring of foot temperature , pressure-relieving therapeutic footwear , and certain surgical interventions prove to be effective . The median effect size found in a total of 23 studies on these interventions is large , over 60 % , and further increases when patients are adherent to treatment . These interventions should be investigated for efficacy as a state-of-the-art integrated foot care approach , where attempts are made to assure treatment adherence . Effect sizes of 75 - 80 % may be expected . If such state-of-the-art integrated foot care is implemented , the majority of problems with foot ulcer recurrence in diabetes can be resolved . It is therefore time to act and to set a new target in diabetic foot care . This target is to reduce foot ulcer incidence with at least 75 % Background Diabetic foot ulcers are frequently related to elevated pressure under a bony prominence . Conservative treatment includes offloading with orthopaedic shoes and custom made orthotics or plaster casts . While casting in plaster is usually effective in achieving primary closure of foot ulcers , recurrence rates are high . Minimally invasive surgical offloading that includes correction of foot deformities has good short and long term results . The surgery alleviates the pressure under the bony prominence , thus enabling prompt ulcer healing , negating the patient ’s dependence on expensive shoes and orthotics , with a lower chance of recurrence . The purpose of this protocol is to compare offloading surgery ( percutaneous flexor tenotomy , mini-invasive floating metatarsal osteotomy or Keller arthroplasty ) to non-surgical treatment for patients with diabetic foot ulcers in a semi-crossover design ed RCT . Methods One hundred patients with diabetic neuropathy related foot ulcers ( tip of toe ulcers , ulcers under metatarsal heads and ulcers under the hallux interphalangeal joint ) will be r and omized ( 2:3 ) to a surgical offloading procedure or best available non-surgical treatment . Group 1 ( surgery ) will have surgery within 1 week . Group 2 ( controls ) will be prescribed an offloading cast applied for up to 12 weeks ( based on clinical considerations ) . Following successful offloading treatment ( ulcer closure with complete epithelization ) patients will be prescribed orthopaedic shoes and custom made orthotics . If offloading by cast for at least 6 weeks fails , or the ulcer recurs , patients will be offered surgical offloading . Follow-up will take place till 2 years following r and omization . Outcome criteria will be time to healing of the primary ulcer ( complete epithelization ) , time to healing of surgical wound , recurrence of ulcer , time to recurrence and complications . Discussion The high recurrence rate of foot ulcers and their dire consequences justify attempts to find better solutions than the non-surgical options available at present . To promote surgery , RCT level evidence of efficacy is necessary . Trial registration Israel MOH_2017–08 - 10_000719 . NIH : NCT03414216 Background Synthesis of multiple r and omized controlled trials ( RCTs ) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions . Filtering of search es is time consuming , and no single method fulfills the principal requirements of speed with accuracy . Automation of systematic review s is driven by a necessity to expedite the Output:	For the prevention of recurrent plantar foot ulcers , multiple RCTs with low risk of bias show the benefit for the use of daily foot skin temperature measurements and consequent preventative actions , as well as for therapeutic footwear that demonstrates to relieve plantar pressure and that is worn by the patient . To prevent recurrence , some evidence exists for integrated foot care when it includes a combination of professional foot treatment , therapeutic footwear and patient education ; for just a single session of patient education , no evidence exists . Surgical interventions can be effective in selected patients , but the evidence base is small . The evidence base to support the use of specific self-management and footwear interventions for the prevention of recurrent plantar foot ulcers is quite strong , but is small for the use of other , sometimes widely applied , interventions and is practically nonexistent for the prevention of a first foot ulcer and non-plantar foot ulcer
MS21942	*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 .Delirium , or acute confusional state , is a common and serious occurrence among hospitalized older persons . Current estimates suggest that delirium complicates hospital stays for more than 2.3 million older persons each year , involving more than 17.5 million hospital days and accounting for more than $ 4 billion ( 1994 dollars ) of Medicare expenditures . A 40 % reduction was recently reported in the risk for delirium among hospitalized older persons receiving a multicomponent targeted risk factor intervention ( MTI ) strategy to prevent delirium , compared with subjects receiving usual hospital care . 1 Before recommending that this preventive strategy be implemented in clinical practice , however , the cost implication s must be thoroughly examined as well . Methods .The present analysis performs net cost evaluations of the MTI for the prevention of delirium among hospitalized patients . Hospital charge and cost-to-charge ratio data are linked to a data base of 852 subjects , who were treated with MTI or usual care . Multivariable regression methods were used to help isolate the impact of MTI on hospital costs . These results were then combined with our earlier work on the impact of the MTI on delirium prevention to assess the cost effectiveness of this intervention . Results .The MTI significantly reduced nonintervention costs among subjects at intermediate risk for developing delirium , but not among subjects at high risk . When MTI intervention costs were included , MTI had no significant effect on overall health care costs in the intermediate risk cohort , but raised overall costs in the high risk group . Conclusions .Because the MTI prevented delirium in the intermediate risk group without raising costs , the conclusion reached is that it is a cost effective treatment option for patients at intermediate risk for developing delirium . In contrast , the results suggest that the MTI is not cost effective for subjects at high risk OBJECTIVE Delirium is a highly prevalent and deleterious disorder in terminally ill cancer patients . We assessed whether a multicomponent preventive intervention was effective in decreasing delirium incidence and severity among cancer patients receiving end-of-life care . METHODS A cohort of 1516 patients was followed from admission to death at seven Canadian palliative care centers . In two of these centers , routine care included a delirium preventive intervention targeting physicians ( written notice on selective delirium risk factors and inquest on intended medication changes ) , patients , and their family ( orientation to time and place , information about early delirium symptoms ) . Delirium frequency and severity were compared between patients at the intervention ( N = 674 ) and usual-care ( N = 842 ) centers based on thrice-daily symptom assessment s with the Confusion Rating Scale . RESULTS The overall rate of adherence to the intervention was 89.7 % . The incidence of delirium was 49.1 % in the intervention group , compared with 43.9 % in the usual-care group ( odds ratio [ OR ] 1.23 , P = 0.045 ) . When confounding variables were controlled for , no difference was observed between the intervention and the usual-care groups in delirium incidence ( OR 0.94 , P = 0.66 ) , delirium severity ( 1.83 vs. 1.92 ; P = 0.07 ) , total days in delirium ( 4.57 vs. 3.57 days ; P = 0.63 ) , or duration of first delirium episode ( 2.9 vs. 2.1 days ; P = 0.96 ) . Delirium-free survival was similar in the two groups . CONCLUSION A simple multicomponent preventive intervention was ineffective in reducing delirium incidence or severity among cancer patients receiving end-of-life care . Delirium prevention remains a difficult challenge in terminally ill cancer patients OBJECTIVES Delirium ( or acute confusional state ) affects 35 % to 65 % of patients after hip-fracture repair , and has been independently associated with poor functional recovery . We performed a r and omized trial in an orthopedic surgery service at an academic hospital to determine whether proactive geriatrics consultation can reduce delirium after hip fracture . DESIGN Prospect i ve , r and omized , blinded . SETTING Inpatient academic tertiary medical center . PARTICIPANTS 126 consenting patients 65 and older ( mean age 79 + /- 8 years , 79 % women ) admitted emergently for surgical repair of hip fracture . MEASUREMENTS Detailed assessment through interviews with patients and design ated proxies and review of medical records was performed at enrollment to ascertain prefracture status . Subjects were then r and omized to proactive geriatrics consultation , which began preoperatively or within 24 hours of surgery , or " usual care . " A geriatrician made daily visits for the duration of the hospitalization and made targeted recommendations based on a structured protocol . To ascertain study outcomes , all subjects underwent daily , blinded interviews for the duration of their hospitalization , including the Mini-Mental State Examination ( MMSE ) , the Delirium Symptom Interview ( DSI ) , and the Memorial Delirium Assessment Scale ( MDAS ) . Delirium was diagnosed using the Confusion Assessment Method ( CAM ) algorithm . RESULTS The 62 patients r and omized to geriatrics consultation were not significantly different ( P>.1 ) from the 64 usual-care patients in terms of age , gender , prefracture dementia , comorbidity , type of hip fracture , or type of surgical repair . Sixty-one percent of geriatrics consultation patients were seen preoperatively and all were seen within 24 hours postoperatively . A mean of 10 recommendations were made throughout the duration of the hospitalization , with 77 % adherence by the orthopedics team . Delirium occurred in 20 /62 ( 32 % ) intervention patients , versus 32 / 64 ( 50 % ) usual-care patients ( P = .04 ) , representing a relative risk of 0.64 ( 95 % confidence interval ( CI ) = 0.37 - 0.98 ) for the consultation group . One case of delirium was prevented for every 5.6 patients in the geriatrics consultation group . There was an even greater reduction in cases of severe delirium , occurring in 7/ 60 ( 12 % ) of intervention patients and 18 / 62 ( 29 % ) of usual-care patients , with a relative risk of 0.40 ( 95 % CI = 0.18 - 0.89 ) . Despite this reduction in delirium , length of stay did not significantly differ between intervention and usual-care groups ( median + /- interquartile range = 5 + /- 2 days in both groups ) , likely because protocol s and pathways predetermined length of stay . In subgroup analyses , geriatrics consultation was most effective in reducing delirium in patients without prefracture dementia or activities of daily living ( ADL ) functional impairment . CONCLUSIONS Proactive geriatrics consultation was successfully implemented with good adherence after hip-fracture repair . Geriatrics consultation reduced delirium by over one-third , and reduced severe delirium by over one-half . Our trial provides strong preliminary evidence that proactive geriatrics consultation may play an important role in the acute hospital management of hip-fracture patients BACKGROUND delirium is a clinical syndrome associated with multiple short and long-term complications and therefore prevention is an essential part of its management . This study was design ed to assess the efficacy of multicomponent intervention in delirium prevention . METHODS a total of 287 hospitalised patients at intermediate or high risk of developing delirium were r and omised to receive a non-pharmacological intervention delivered by family members ( 144 patients ) or st and ard management ( 143 patients ) . The primary efficacy outcome was the occurrence of delirium at any time during the course of hospitalisation . Three vali date d observers performed the event adjudication by using the confusion assessment method screening instrument . RESULTS there were no significant differences in the baseline characteristics between the two groups . The primary outcome occurred in 5.6 % of the patients in the intervention group and in 13.3 % of the patients in the control group ( relative risk : 0.41 ; confidence interval : 0.19 - 0.92 ; P = 0.027 ) . CONCLUSION the results of this study show that there is a benefit in the non-pharmacological prevention of delirium using family members , when compared with st and ard management of patients at risk of developing this condition BACKGROUND older people undergoing elective surgery have significant post-operative problems prolonging hospitalisation . OBJECTIVE to design , embed , and evaluate an evidence -based comprehensive geriatric assessment ( CGA ) service for at-risk older patients undergoing elective surgery . SETTING urban teaching hospital . SUBJECTS elective surgical patients aged 65 + . INTERVENTION multidisciplinary preoperative CGA service with post-operative follow-through ( proactive care of older people undergoing surgery [ ' POPS ' ] ) . METHODS observational cohort study and multilevel surveys ( development and modelling phase ) . Prospect i ve ' before and after ' comparison ( exploratory evaluation ) . RESULTS findings from the development phase showed high levels of preoperative co-morbidity , no multidisciplinary preoperative input , and multiple potentially preventable post-operative problems delaying discharge in older elective surgery patients . Comparison of 2 cohorts of elective orthopaedic patients ( pre-POPS vs POPS , N = 54 ) showed the POPS group had fewer post-operative medical complications including pneumonia ( 20 % vs 4 % [ p = 0.008 ] ) and delirium ( 19 % vs 6 % [ p = 0.036 ] ) , and significant improvements in areas reflecting multidisciplinary practice including pressure sores ( 19 % vs 4 % [ p = 0.028 ] ) , poor pain control ( 30 % vs 2 % [ p<0.001 ] ) , delayed mobilisation ( 28 % vs 9 % [ p = 0.012 ] ) and inappropriate catheter use ( 20 % vs 7 % [ p = 0.046 ] ) . Length of stay was reduced by 4.5 days . There were fewer delayed discharges relating to medical complications ( 37 % vs 13 % ) or waits for OT assessment or equipment ( 20 % vs 4 % ) . CONCLUSION a proactive evidence -based CGA service for at-risk older elective surgical patients was developed according to MRC framework for complex interventions . Pre/post comparison in elective orthopaedic patients showed improved ( within method ological limitations ) post-operative outcomes indicative of better clinical effectiveness and efficiency , and contributed to the service obtaining mainstream funding . Informed by the present study , a r and omised controlled trial is ongoing Background and aims : Delirium is a common postoperative complication in elderly patients which has a serious impact on outcome in terms of morbidity and costs . We examined whether a postoperative multi-factorial intervention program can reduce delirium and improve outcome in patients with femoral neck fractures . Methods : One hundred and ninety-nine patients , aged 70 years and over ( mean age±SD , 82±6 , 74 % women ) , were r and omly assigned to postoperative care in a specialized geriatric ward or a conventional orthopedic ward . The intervention consisted of staff education focusing on the assessment , prevention and treatment of delirium and associated complications . The staff worked as a team , applying comprehensive geriatric assessment , management and rehabilitation . Patients were assessed using the Mini Mental State Examination and the Organic Brain Syndrome Scale , and delirium was diagnosed according to DSM-IV criteria . Results : The number of days of postoperative delirium among intervention patients was fewer ( 5.0±7.1 days vs 10.2±13.3 days , p=0.009 ) compared with controls . A lower proportion of intervention patients were delirious postoperatively than controls ( 56/102 , 54.9 % vs 73/97 , 75.3 % , p=0.003 ) . Eighteen percent in the intervention ward and 52 % of controls were delirious after the seventh postoperative day ( p<0.001 ) . Intervention patients suffered from fewer complications , such as decubitus ulcers , urinary tract infections , nutritional complications , sleeping problems and falls , than controls . Total postoperative hospitalization was shorter in the intervention ward ( 28.0±17.9 days vs 38.0±40.6 days , p=0.028 ) . Conclusions : Patients with postoperative delirium can be successfully treated , result ing in fewer days of delirium , fewer other complications , and shorter length of hospitalization OBJECTIVES To investigate whether an education program and a reorganization of nursing and medical care improved the outcome for older delirious patients . DESIGN Prospect i ve intervention study . SETTING Department of General Internal Medicine , Sundsvall Hospital , Sweden . PARTICIPANTS Four hundred patients , aged 70 and older , consecutively admitted to an intervention or a control ward . INTERVENTION The intervention consisted of staff education focusing on the assessment , prevention , and treatment of delirium and on caregiver-patient interaction . Reorganization from a task-allocation care system to a patient-allocation system with individualized care . MEASUREMENTS The patients were assessed using the Organic Brain Syndrome Scale and the Mini-Mental State Examination on Days 1 , 3 , and 7 after admission . Delirium was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria . RESULTS Delirium was equally common on the day of admission at the two wards , but fewer patients remained delirious on Day 7 on the intervention ward ( n=19/6 Output:	The evidence from 19 studies that met the inclusion criteria suggests that most multicomponent interventions are effective in preventing onset of delirium in at-risk patients in a hospital setting .
MS21943	*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 determine the effect of antibiotic treatment for acute otitis media in children between 6 months and 2 years of age . Design : Practice based , double blind , r and omised , placebo controlled trial . Setting : 53 general practice s in the Netherl and s. Subjects : 240 children aged 6 months to 2 years with the diagnosis of acute otitis media . Intervention : Amoxicillin 40 mg/kg/day in three doses . Main outcome measures : Persistent symptoms at day four and duration of fever and pain or crying , or both . Otoscopy at days four and 11 , tympanometry at six weeks , and use of analgesic . Results : Persistent symptoms at day four were less common in the amoxicillin group ( risk difference 13 % ; 95 % confidence interval 1 % to 25 % ) . The median duration of fever was two days in the amoxicillin group versus three in the placebo group ( P=0.004 ) . No significant difference was observed in duration of pain or crying , but analgesic consumption was higher in the placebo group during the first 10 days ( 4.1 v 2.3 doses , P=0.004 ) . In addition , no otoscopic differences were observed at days four and 11 , and tympanometric findings at six weeks were similar in both groups . Conclusions : Seven to eight children aged 6 to 24 months with acute otitis media needed to be treated with antibiotics to improve symptomatic outcome at day four in one child . This modest effect does not justify prescription of antibiotics at the first visit , provided close surveillance can be guaranteed CONTEXT The emergence and spread of antibiotic-resistant Streptococcus pneumoniae in US communities is due , in part , to the excessive use of antibiotics for acute respiratory tract infections . OBJECTIVE To decrease total antibiotic use for uncomplicated acute bronchitis in adults . DESIGN Prospect i ve , nonr and omized controlled trial , including baseline ( November 1996-February 1997 ) and study ( November 1997-February 1998 ) periods . SETTING Four selected primary care practice s belonging to a group-model health maintenance organization in the Denver , Colo , metropolitan area . PARTICIPANTS Consecutive adults diagnosed as having uncomplicated acute bronchitis . A total of 2462 adults were included at baseline and 2027 adults were included in the study . Clinicians included 56 physicians , 28 physician assistants or nurse practitioners , and 9 registered nurses . INTERVENTION The full intervention site received household and office-based patient educational material s , as well as a clinician intervention consisting of education , practice -profiling , and academic detailing . A limited intervention site received only office-based educational material s , and control sites provided usual care . MAIN OUTCOME MEASURE Antibiotic prescriptions for uncomplicated acute bronchitis during baseline and study periods . RESULTS Antibiotic prescription rates for uncomplicated acute bronchitis were similar at all 4 sites during the baseline period . During the study period , there was a substantial decline in antibiotic prescription rates at the full intervention site ( from 74 % to 48 % [ P = .003 ] ) , but not at the control and limited intervention sites ( 78 % to 76 % [ P = .81 ] and 82 % to 77 % [ P = .68 ] , respectively ) . Compared with control sites , changes in nonantibiotic prescriptions ( inhaled bronchodilators , cough suppressants , and analgesics ) were not significantly different for intervention sites . Return office visits ( within 30 days of the incident visit ) for bronchitis or pneumonia did not change significantly for any of the sites . CONCLUSIONS Antibiotic treatment of adults diagnosed as having uncomplicated acute bronchitis can be safely reduced using a combination of patient and clinician interventions BACKGROUND Overuse of antibiotics for children 's upper respiratory infections is widespread and contributes to the emergence of antibiotic-resistant bacteria . OBJECTIVE To assess changes in knowledge and awareness regarding antibiotic resistance and appropriate antibiotic use after community-wide educational interventions to reduce inappropriate antibiotic use . DESIGN Baseline survey conducted during June through July 1997 and postintervention survey of baseline participants during June through August 1998 . SETTING Communities in northern Wisconsin . PARTICIPANTS Parents of 729 r and omly selected children < 4 years of age were called until 215 in each of the intervention and control areas were reached . Of the 430 baseline participants , 365 ( 85 % ) participated in the postintervention survey . INTERVENTION Parent-oriented activities included distribution of material s and presentations . Physician-oriented activities included formal presentations and small group meetings . OUTCOME MEASURE Change in awareness about antibiotic resistance and knowledge about antibiotic indications . RESULTS A higher proportion of parents in the intervention area ( 53 % ) were exposed to 2 or more local educational messages , compared with the control area ( 23 % ) . From the baseline to the postintervention survey , the percentage of parents with a high degree of antibiotic resistance awareness increased more in the intervention area ( 58 % to 73 % ) than in the control area ( 60 % to 65 % ) . In the intervention area , there was also a larger increase in knowledge regarding appropriate indications for antibiotic use , compared with the control area . The proportion of parents who expected an antibiotic for their child and did not receive one declined in the intervention area ( 14 % to 9 % ) , while it increased in the control area ( 7 % to 10 % ) . In addition , the percentage of parents in the intervention area who brought their child to another physician because they did not receive an antibiotic decreased ( 5 % to 2 % ) , while it increased in the control area ( 2 % to 4 % ) . CONCLUSION Parental knowledge and awareness about antibiotic indications and antibiotic resistance can be changed with educational interventions directed at parents and clinicians Abstract Objective : To assess three prescribing strategies for sore throat . Design : R and omised follow up study . Setting : 11 general practice s in the South and West region . Subjects : 716 patients aged 4 years and over with sore throat and an abnormal physical sign in the throat ; 84 % had tonsillitis or pharyngitis . Patients were r and omised to three groups : prescription for antibiotics for 10 days ( group 1 , 246 patients ) ; no prescription ( group 2 , 230 patients ) ; or prescription for antibiotics if symptoms were not starting to settle after three days ( group 3 ; 238 patients ) . Main outcome measures : Duration of symptoms ; satisfaction and compliance with and perceived efficacy of antibiotics ; time off school or work . Outcomes were documented in 582 subjects ( 81 % ) . Results : Median duration of antibiotic use differed significantly in the three groups ( 10 v 0 v 0 days , P<0.001 ) ; 69 % of patients in group 3 did not use their prescription . The proportion of patients better by day 3 did not differ significantly ( 37 % v 35 % v 30 % , P=0.28 ) , nor did the duration of illness ( median 4 v 5 v 5 days , P=0.39 ) , days off work or school ( median 2 v 2 v 1 , P=0.13 ) , or proportion of patients satisfied ( 96 % v 90 % v 93 % , P=0.09 ) , although group 1 had fewer days of fever ( median 1 v 2 v 2 days , P=0.04 ) . More patients in group 1 thought the antibiotics were effective ( 87 % v 55 % v 60 % , P<0.001 ) and intended coming to the doctor in future attacks ( 79 % v 54 % v 57 % , P<0.001 ) . “ Legitimation ” of illness — to explain to work or school ( 60 % ) or family or friends (37%)–was an important reason for consultation . Patients who were more satisfied got better more quickly , and satisfaction related strongly to how well the doctor dealt with patient 's concerns . Conclusion : Prescribing antibiotics for sore throat only marginally affects the resolution of symptoms but enhances belief in antibiotics and intention to consult in future when compared with the acceptable strategies of no prescription or delayed prescription . Psychosocial factors are important in the decision to see a general practitioner and in predicting the duration of illness . Key messages Sore throat is one of the commonest presentations of upper respiratory illness to general practitioners , and attendance is increasing Prescribing antibiotics for sore throat does not reduce the extent and duration of symptoms Prescribing antibiotics enhances belief in antibiotics and intention to consult Legitimation of illness is an important reason for attending the doctor Satisfaction predicts duration of illness and closely relates to how well concerns are dealt with — unless patients are very ill , general practitioners should consider exploring concerns and should avoid or delay prescribing OBJECTIVES To identify which children with acute otitis media are at risk of poor outcome and to assess benefit from antibiotics in these children . DESIGN Secondary analysis of r and omised controlled trial cohort . SETTING Primary care . PARTICIPANTS 315 children aged 6 months to 10 years . INTERVENTION Immediate or delayed ( taken after 72 hours if necessary ) antibiotics . MAIN OUTCOME MEASURE Predictors of short term outcome : an episode of distress or night disturbance three days after child saw doctor . RESULTS Distress by day three was more likely in children with high temperature ( adjusted odds ratio 4.5 , 95 % confidence interval 2.3 to 9.0 ) , vomiting ( 2.6,1.3 to 5.0 ) , and cough ( 2.0 , 1.1 to 3.8 ) on day one . Night disturbance by day three was more likely with high temperature 2.4 ( 1.2 to 4.8 ) , vomiting ( 2.1,1.1 to 4.0 ) , cough ( 2.3,1.3 to 4.2 ) , and ear discharge ( 2.1 , 1.2 to 3.9 ) . Among the children with high temperature or vomiting , distress by day three was less likely with immediate antibiotics ( 32 % for immediate v 53 % for delayed , chi2=4.0 ; P=0.045 , number needed to treat 5 ) as was night disturbance ( 26 % v 59 % , chi2=9.3 ; P=0.002 ; number needed to treat 3 ) . In children without higher temperature or vomiting , immediate antibiotics made little difference to distress by day three ( 15 % v 19 % , chi2=0.74 ; P=0.39 ) or night disturbance ( 20 % v 27 % , chi2=1.6 ; P=0.20 ) . Addition of cough did not significantly improve prediction of benefit . CONCLUSION In children with otitis media but without fever and vomiting antibiotic treatment has little benefit and a poor outcome is unlikely Abstract Objective : To assess the medicalising effect of prescribing antibiotics for sore throat . Setting : 11 general practice s in Engl and . Design : R and omised trial of three approaches to sore throat : a 10 day prescription of antibiotics , no antibiotics , or a delayed prescription if the sore throat had not started to settle after three days . Patients : 716 patients aged 4 and over with sore throat and an abnormal physical sign : 84 % had tonsillitis or pharyngitis . Outcome measures : Number and rate of patients making a first return with sore throat , pharyngitis , or tonsillitis . Early returns ( within two weeks ) and complications ( otitis media , sinusitis , quinsy ) . Outcomes were documented in 675 subjects ( 94 % ) . Results : Mean follow up time was similar ( antibiotic group 1.07 years , other two groups 1.03 years ) . More of those initially prescribed antibiotics initially returned to the surgery with sore throat ( 38 % v 27 % , adjusted hazard ratio for return 1.39 , 95 % confidence interval 1.03 to 1.89 ) . Antibiotics prescribed for sore throat during the previous year had an additional effect ( hazard ratio 1.69 , 1.20 to 2.37 ) . Longer duration of illness ( > 5 days ) was associated with increased return within six weeks ( hazard ratio 2.90 , 1.70 to 4.92 ) . Prior attendance with upper respiratory conditions was also associated with increased reattendance . There was no difference between groups in early return ( 13/238 ( 5.5 % ) v 27/437 ( 6 % ) ) , or complications ( 2/236 ( 0.8 % ) v3/434 ( 0.7 % ) ) . Conclusions : Complications and early return result ing from no or delayed prescribing of antibiotics for sore throat are rare . Both current and previous prescribing for sore throat increase reattendance . To avoid medicalising a self limiting illness doctors should avoid antibiotics or offer a delayed prescription for most patients with sore throat . Key messages Sore throat is one of the commonest presentations of upper respiratory illness in primary care and attendence is increasing Complications are rare with no , or delayed , antibiotic prescription Prescribing antibiotics increases reattendance for future episodes Unless patients are very ill general practitioners should consider exploring concerns , explain the natural history , and avoid or delay prescribing Abstract Objective Output:	CONCLUSION The consistent reduction in antibiotic usage in the five controlled trials included in this review suggests that delayed prescription is an effective means of reducing antibiotic usage for acute respiratory infections .
MS21944	*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: Benzydamine hydrochloride rinse was shown to prevent oral mucositis in radiation therapy . Prevention of mucositis allows reduction in morbidity of one of the therapy limiting complications of radiotherapy for cancer therapy OBJECTIVE To assess the microbiological effects of an antiseptic , non-alcohol based mouth-rinse containing chlorhexidine and cetylpyridinium chloride , in patients undergoing radiation therapy for head- and -neck cancer . STUDY DESIGN This was a parallel , double-blind , prospect i ve , r and omized clinical trial , including patients irradiated as part of the therapy of head- and -neck cancer , aged 18 - 75 , with at least 10 teeth , and willing to sign an informed consent . Cancer patients were r and omly assigned to one of the two treatments ( test mouth-rinse or a placebo ) . Three visits were scheduled ( baseline , 14 and 28 days ) . Microbiological findings were evaluated in tongue , mucosa and subgingival sample s , by means of culture . Microbiological variables were assessed by means of the Mann-Whitney , Wilcoxon and chi-square tests . RESULTS 70 patients were screened and 36 were included . The detection of C and ida species in mucosa and tongue sample s showed significant reductions in the test group . Total bacterial counts decreased in both groups from baseline to the 2-week visit , while minor changes occurred between 2 and 4 weeks ( effects on P. gingivalis , P. intermedia , C. rectus , E. corrodens ) . CONCLUSIONS Within the limitations of the small sample size , this study suggests that the use of the tested mouth-rinse may lead to improvements in microbiological parameters in patients irradiated for head- and -neck cancer Patients receiving cytotoxic antineoplastic therapy often have treatment-associated stomatitis . A 0.12 % chlorhexidine digluconate mouthrinse was evaluated ( 15 ml , three times a day ) in a prospect i ve , double-blind r and omized trial as prophylaxis against cytotoxic therapy-induced damage to oral soft tissues . Seventy subjects , forty in patients receiving high-dose chemotherapy and thirty out patients receiving high-dose head and neck radiation therapy , were evaluated . Chlorhexidine mouthrinse significantly reduced the incidence of oral mucositis in the chemotherapy group on day 14 ( p less than 0.02 ) and at 1 week follow-up on day 28 ( p less than 0.002 ) . Mucositis in the patients undergoing chemotherapy who received chlorhexidine also resolved more rapidly . Mucositis severity was significantly less compared to the control chemotherapy group on day 14 ( p less than 0.03 ) , day 21 ( p less than 0.04 ) , and on 1 week follow-up ( p less than 0.02 ) . Concomitant trends in the reduction in oral streptococci and yeast were noted in the chemotherapy group receiving chlorhexidine mouthrinse . Although no differences were observed in oral mucositis between the control and chlorhexidine groups of patients undergoing high-dose radiotherapy , similar reductions of oral microflora to those seen in the chemotherapy population were also noted for patients undergoing radiation therapy who received chlorhexidine . Although generally not significant , some increase in gram-negative bacilli was noted in the chlorhexidine-treated patients in both the chemotherapy and radiotherapy groups , but there was no correlation with increased systemic infection . Prophylactic chlorhexidine mouthrinse reduces oral mucositis and microbial burden in patients with cancer undergoing intensive chemotherapy Oral mucosal ulceration complicating bone marrow transplantation interferes with patients ' comfort , nutrition and may lead to systemic infection derived from the mouth . The mucosal injury results from epithelial damage due to the cytotoxic effects of chemotherapy and radiation conditioning as well as from superficial oropharyngeal infection . Because chlorhexidine gluconate is a broad spectrum topical antimicrobial which has been demonstrably effective in preventing oral infection and gingivitis , we performed a r and omized , placebo controlled , double-blind trial of chlorhexidine as a mouth rinse in BMT recipients to study the severity of oral mucositis and both oral and systemic infectious complications . One hundred patients were r and omly assigned to receive either chlorhexidine gluconate 0.12 % mouth rinse or placebo three times daily from the initiation ( day -8 ) of chemoradiotherapy conditioning until day + 35 post-BMT . Chlorhexidine use result ed in a trend toward improved oral hygiene index ( reduced dental plaque ) ( p = 0.06 ) but did not modify the oral mucositis . Patients using chlorhexidine developed a maximum ulceration of 18 + /- 22 % of their oral mucosa , while placebo patients ulcerated 25 + /- 31 % of the mouth . Ulcerative mucositis was significantly worse in adults compared with children , in individuals who received methotrexate for graft-versus-host disease prophylaxis , and was most prominent on non-keratinized epithelium . Overall , there was no clinical ly demonstrable additional therapeutic advantage to the use of chlorhexidine in either reducing the mucositis , controlling oral pain , facilitating oral nutrition , shortening hospital stay , or reducing oral infection with herpes simplex virus . There was a trend toward diminished oral c and idiasis in chlorhexidine users ( p = 0.06 ) . ( ABSTRACT TRUNCATED AT 250 WORDS PURPOSE To determine whether a chlorhexidine mouthwash could alleviate radiation-induced oral mucositis . PATIENTS AND METHODS Patients scheduled to receive radiation therapy to include greater than one third of the oral cavity mucosa were selected for study . Following stratification , they were r and omized in a double-blind manner to receive a chlorhexidine mouthwash or a placebo mouthwash . Both groups were then similarly evaluated for mucositis and mouthwash toxicity . RESULTS Twenty-five patients were r and omized to receive the chlorhexidine mouthwash , while 27 received the placebo mouthwash . Treatment arms were well balanced . There was a trend for more mucositis and there was substantially more toxicity ( eg , mouthwash-induced discomfort , taste alteration , and teeth staining ) on the chlorhexidine arm . CONCLUSION In contrast to the pre study hypothesis that a chlorhexidine mouthwash might provide benefit for patients receiving radiation therapy to the oral mucosa , this study provides strong evidence suggesting that a chlorhexidine mouthwash is detrimental in this clinical situation PURPOSE / OBJECTIVES To test the effectiveness of a nurse-initiated systematic oral hygiene teaching program-PRO-SELF : Mouth Aware (PSMA)-in conjunction with two mouthwashes ( 0.12 % chlorhexidine or sterile water ) in preventing chemotherapy-induced oral mucositis . DESIGN R and omized , double-blind , placebo-controlled , clinical trial . SETTING S 23 outpatient clinics and office practice s in California . SAMPLE 222 patients who were starting a cycle of mucositis-inducing chemotherapy . METHOD Participants were followed over three chemotherapy cycles . All patients were provided the PSMA program . R and om assignment to a mouthwash occurred prior to the development of oral mucositis . Research ers used the Oral Assessment Guide to assess the patients oral cavities monthly ( with the patients cycles of chemotherapy ) and when patients reported any oral changes between cycles . MAIN RESEARCH VARIABLES Type of mouthwash , incidence , days to onset , and severity of chemotherapy-induced oral mucositis . FINDINGS No significant differences existed between the two mouthwashes in regard to incidence , days to onset , and severity of mucositis . CONCLUSIONS Because chlorhexidine ( S20 per pint ) was no more effective than water , a substantial cost savings can be realized by rinsing with water . Interestingly , the PSMA program appeared to reduce the incidence of mucositis from on a prior estimate of 44 % to less than 26 % . IMPLICATION S FOR NURSING PRACTICE A nursing prescription of a systematic oral hygiene program using water as a mouth rinse is cost efficient and may be effective in preventing oral mucositis The goal of reducing oral complications during chemotherapy and bone marrow transplantation has received attention at several centers . The current r and omized study of 86 adults with leukemia treated with chemotherapy or bone marrow transplantation assessed the potential role of chlorhexidine , nystatin , and saline solution rinses to reduce the findings of oral mucositis , gingivitis , and oral infection . The results of this study did not show a reduction in mucositis with the use of these rinses . However , potential bacterial and fungal pathogens were identified less frequently in the patients using chlorhexidine rinse OBJECTIVE To assess the effects of an antiseptic , non-alcohol based mouth-rinse containing chlorhexidine and cetylpyridinium chloride , in preventing the oral complications associated to radiation therapy in head- and -neck cancer patients . STUDY DESIGN This was a parallel , double blind , prospect i ve , r and omized clinical trial . Cancer patients were r and omly assigned to one of the two treatments ( test mouth-rinse or a placebo ) . Three visits were scheduled ( baseline , 14 and 28 days ) . Different outcome variables were evaluated : mucositis , plaque and gingival indices , stimulated saliva and salivary pH. RESULTS 70 patients were screened and 36 were included . The presence and the degree of mucositis significantly increased in both groups and no significant differences were detected between groups , although the median increase in the placebo group ( 1.81 ) at 2 weeks was higher than in the test group ( 1.20 ) . CONCLUSIONS Within the limitations of the small sample size , this study suggests that the use of the tested mouth-rinse may lead to some improvements in clinical parameters in patients irradiated for head- and -neck cancer AIMS The present study was done to assess the effect of three alcohol-free mouthwashes on radiation-induced oral mucositis in patients with head and neck malignancies . MATERIAL S AND METHODS Eighty patients with head and neck malignancies , scheduled to undergo curative radiotherapy , were r and omly assigned to receive one of the three alcohol-free test mouthwashes ( 0.12 % chlorhexidine , 1 % povidone-iodine , or salt/soda ) or a control . The patients were instructed to rinse with 10 ml of the mouthwash , twice a day , for a period of 6 weeks . Mucositis was assessed at baseline and at weekly intervals during radiation therapy , using the World Health Organization criteria for grading of mucositis . The baseline demography of the four groups was matched for age , sex , stage of cancer , and whether the patient had cancer of oral or extraoral regions . A post hoc test for repeated measures was used to find the difference of mean mucositis scores between the groups at various week intervals . RESULTS Among the 76 patients who completed the study , patients in the povidone-iodine group had significantly lower mucositis scores when compared to the control group from the first week of radiotherapy . Their scores were also significantly lower when compared to the salt/soda and chlorhexidine groups from the fourth and fifth week , respectively , after radiotherapy . CONCLUSIONS This study demonstrates that use of alcohol-free povidone-iodine mouthwash can reduce the severity and delay the onset of oral mucositis due to antineoplastic radiotherapy Conditioning chemoradiotherapy damages the mucosal barrier of the mouth and throat and often produces severe oral inflammation and infection . In a prospect i ve , double-blind , r and omized study , we examined the use of a chlorhexidine digluconate mouthrinse for prophylaxis against oral mucosal complications in 51 bone marrow transplant patients . Use of chlorhexidine mouthrinse produced significant reductions in the incidence and severity of oral mucositis . Mucositis also resolved more quickly in patients receiving chlorhexidine . Concomitant reductions in total oral streptococci ( p less than 0.02-p less than 0.001 ) and oral c and ida ( p less than 0.004 ) were seen in patients using chlorhexidine . Persistent clinical oral c and idiasis ( thrush ) was observed in 15 to 27 control group patients ( 56 % ) , but only transiently in two ( 8 % ) of 24 patients who used chlorhexidine rinse ( p less than 0.001 ) . Five of 27 control group patients ( 19 % ) had c and idemia , while no c and idemia was observed in the chlorhexidine group ( p less than 0.03 ) . Three deaths from disseminated c and idiasis occurred in the placebo group ; none occurred in patients who received chlorhexidine . Prophylactic use of chlorhexidine mouthrinse produces reductions in oral soft tissue disease and oral microbial burden in patients undergoing bone marrow transplantation . The reductions in mucositis and in oral c and ida infections observed with prophylactic chlorhexidine mouthrinse represent a significant advantage for patients undergoing marrow transplantation Mucositis induced by irradiation is the Output:	CONCLUSIONS This systematic review found that chlorhexidine is not significantly effective in reducing the severity of mucositis ( moderate quality of evidence ) nor in preventing the incidence of mucositis ( low quality of evidence ) .
MS21945	*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: Migraine is associated with stimulus hypersensitivity , increased evoked cortical responses , and abnormal 5-HT levels in peripheral blood . We studied cortical auditory evoked potentials ( AEPs ) between attacks in 35 patients suffering from migraine without aura ( MO , n = 25 ) or with aura ( MA , n = 10 ) and in 25 healthy volunteers . Binaural tones were delivered at 40 , 50 , 60 , and 70 dB sensation level ( SL ) in a pseudor and omized order . The intensity dependence of the auditory Nl-P2 component was significantly greater in MO ( p = 0.003 ) and MA ( p = 0.02 ) patients than in healthy controls , result ing in a much steeper amplitudeistimulus intensity function slope . When three sequential blocks of 40 averaged responses were analyzed at the 40- and 70-dB SL intensities , N1–P2 amplitude decreased in second and third blocks at both intensities in controls , but increased in migraineurs , a difference that was significant in both blocks for the 70-dB SL stimulus . The strong interictal dependence of AEPs on stimulus intensity may thus be due to potentiation ( instead of habituation ) of the response during repetition of the high-intensity stimulation . In concordance with previous studies of visual evoked potentials , these results confirm that migraine is characterized between attacks by an abnormality of cortical information processing , which might be a consequence of low 5-HT transmission and favor cortical energy dem and Purpose The tracer 123I-2-([2-({dimethylamino}methyl)phenyl]thio)-5-iodophenylamine ( [123I]ADAM ) has been developed to image serotonin transporters ( SERTs ) with SPECT . Pre clinical studies have shown that [123I]ADAM binds selectively to SERTs . Moreover , initial human studies have shown that [123I]ADAM binding could be blocked by selective serotonin reuptake inhibitors ( SSRIs ) . However , in humans it has not been proven that [123I]ADAM binds selectively to SERTs . Methods We examined the in vivo availability of SERTs in 12 healthy young volunteers 5 h after bolus injection of [123I]ADAM . To evaluate the selectivity of binding , four participants were pretreated ( double-blinded design ) with placebo , four with paroxetine ( 20 mg ) and four with the dopamine/norepinephrine blocker methylpheni date ( 20 mg ) . SPECT studies were performed on a brain-dedicated system ( Neurofocus ) , and the SPECT images were coregistered with individual MR scans of the brain . ADAM binding in SERT-rich brain areas and cerebellar cortex ( representing non-specific binding ) was assessed by drawing regions of interest ( ROIs ) on the individual MR images . Specific to non-specific ratios were used as the outcome measure . Results We found that specific to non-specific ratios were statistically significantly lower in paroxetine-pretreated participants than in placebo- or methylpheni date -pretreated participants . No such difference was found between groups pretreated with placebo or methylpheni date . Conclusion Our preliminary findings suggest that [123I]ADAM binds selectively to SERTs in human brain Identification of a biomarker that can inform on extracellular serotonin ( 5-HT ) levels in the brains of living humans would enable greater underst and ing of the way brain circuits are modulated by serotonergic neurotransmission . Substantial evidence from studies in animals and humans indicates an inverse relationship between central 5-HT tonus and 5-HT type 4 receptor ( 5-HT4R ) density , suggesting that 5-HT4R receptor density may be a biomarker marker for 5-HT tonus . Here , we investigated whether a 3-week administration of a selective serotonin reuptake inhibitor , expected to increase brain 5-HT levels , is associated with a decline in brain 5-HT4R binding . A total of 35 healthy men were studied in a placebo-controlled , r and omized , double-blind study . Participants were assigned to receive 3 weeks of oral dosing with placebo or fluoxetine , 40 mg per day . Brain 5-HT4R binding was quantified at baseline and at follow-up with [11C]SB207145 positron emission tomography ( PET ) . Three weeks of intervention with fluoxetine was associated with a 5.2 % reduction in brain 5-HT4R binding ( P=0.017 ) , whereas placebo intervention did not change 5-HT4R binding ( P=0.52 ) . Our findings are consistent with a model , wherein the 5-HT4R density adjusts to changes in the extracellular 5-HT tonus . Our data demonstrate for the first time in humans that the imaging of central 5-HT4R binding may be used as an in vivo biomarker of the central 5-HT tonus Objective : The 5-HT1B/D agonists ( triptans ) are specific headache medications that have no effect on pain as such . Although they are routinely used in the treatment of acute migraine attacks , the underlying mechanisms of action are still a matter of debate . Methods : Forty-three healthy participants underwent fMRI while receiving trigemino-nociceptive stimulation and control stimuli in a st and ardized fMRI paradigm . Using a crossover , double-blind , placebo-controlled design , 21 participants ( 10 women , mean age 26.9 , range 20–37 years ) received sumatriptan and 22 participants ( 11 women , mean age 25.5 , range 22–32 years ) received acetylsalicylic acid ( ASA ) . Administration of medication and saline was r and omized between participants of each group result ing in half of the participants receiving saline and the other half receiving the respective medication during the first fMRI data acquisition . Results : While mean pain intensity ratings did not differ significantly between control and medication nor between medications , we found a significant blood oxygen level – dependent signal increase in the trigeminal nuclei and the thalamus after sumatriptan treatment compared with placebo or ASA . In addition , we specifically looked for the pharmacologic modulation of functional coupling between trigeminal nuclei and higher brain areas , i.e. , trigemino-cortical pathways , and found a strong coupling during the saline condition , which was altered by sumatriptan but not after ASA administration . Conclusion : These data suggest that a specific functional inhibition of trigemino-cortical projections is one of the reasons that triptans , unlike pain killers , act highly specifically on headache and migraine but not pain as such Background : Altered serotonin ( 5-HT ) neurotransmission has been implicated in the pathophysiology of migraine headache . Objectives : To test this hypothesis in migraine patients in vivo using PET and α-[11C]methyl-l-tryptophan as a surrogate marker of brain 5-HT synthetic rate during different phases of their migraine attack and after acute antimigraine therapy with sumatriptan , and to compare them with normal controls . Methods : Six patients were scanned 1 ) within 6 hours after the onset of a spontaneous migraine attack , 2 ) 2 hours after subcutaneous sumatriptan , and 3 ) interictally when migraine free for at least 3 days . Head pain was rated before each scan , and before and every 15 minutes after sumatriptan . Results : Brain 5-HT synthesis was highest during attacks , lowest after sumatriptan , and intermediate when patients were migraine free . All states were statistically different from the others in virtually all brain regions examined . 5-HT synthetic rates in patients during migraine attacks did not differ from those of age- and sex-matched controls , whereas they were significantly lower after sumatriptan in a majority of regions . Interictally , global brain 5-HT synthetic rate was slightly , albeit not significantly , lower ( −14 % ) in migraine patients than in controls , with specific cortical areas exhibiting proportionally more severe reductions ( −28 % to 31 % ) . Conclusions : These findings point to a low cortical serotonergic tone in migraine patients interictally . Further , they demonstrate widespread increases in brain serotonin ( 5-HT ) synthetic rate in migraine patients during attacks , and that triptans exert a negative feedback regulation of brain 5-HT synthesis concurrently with modulation of pain pathways Objective .—To investigate the effects of fluoxetine in migraine prophylaxis on habituation of visually evoked potentials Abstract Objective : Triptans are highly effective in the treatment of migraine . Both central and peripheral mechanisms of action have been suggested . Until now , firm data about the passage of triptans into the CNS in humans have been lacking . The aim of the current study was to evaluate , using positron emission tomography ( PET ) , the uptake and distribution of zolmitriptan into the CNS after intranasal administration . Subjects and methods : Eight healthy volunteers , five males and three females ( mean ages 23 and 26 years , respectively ) , were included . Radioactive [carbonyl-11C]zolmitriptan was infused intravenously for 5 minutes on two occasions : once alone , and once 30–40 minutes after intranasal administration of unlabelled zolmitriptan 5 mg . PET was used to measure the concentration of labelled zolmitriptan in the brain , from the start of the tracer infusion for 90 minutes . Regional cerebral blood volume was determined with [15O]carbon monoxide . In addition , an MRI scan was performed to obtain anatomical information . The PET images were analysed quantitatively for different areas of the brain , generating [11C]zolmitriptan time-activity data corrected for circulating tracer activity . The rate of uptake of intranasal zolmitriptan into the CNS was estimated by kinetic modelling using the PET data . Results : PET data from this study demonstrate a rapid dose-proportional uptake of [11C]zolmitriptan into the brain . Significant concentrations of [11C]zolmitriptan were found in all brain regions studied . Calculated CNS concentrations after intranasal zolmitriptan administration showed a gradual increase , reaching about 2nM ( 0.5 μg/L ) 30 minutes after administration and 3.5nM ( 1.0 μg/L ) , or one-fifth of the plasma concentration , 1 hour after administration . Five minutes after zolmitriptan administration , the mean CNS concentration had already reached 0.5nM , which is higher than in vitro values for initiation of the agonistic action on 5-HT1B/1D receptors . Conclusion : This study demonstrates by direct measurements that zolmitriptan enters the brain parenchyma in humans , achieving an uptake rate and concentration compatible with a central mode of action As shown in animal studies , 5HT1B/1D agonists can inhibit activity in the trigeminal nucleus caudalis , which may be advantageous for their antimigraine effect . To demonstrate a possible central nervous system ( CNS ) action of these compounds in man we studied their effect on the intensity dependence of the cortical auditory evoked potentials ( IDAPs ) , thought to be inversely related to central serotonergic transmission . An amplitude/stimulus intensity function ( ASF ) slope was computed in healthy volunteers and migraine patients between attacks before and 2 h after oral 311C90 ( zolmitriptan “ Zomig ” ) 10 mg ( n=14 ) , 311C90 5 mg ( n=7 ) , sumatriptan 100 mg ( n=14 ) , dexfenfluramine 15 mg ( n=4 ) , lorazepam 1.25 mg ( n=4 ) and placebo ( n=14 ) . 311C90 10 mg and , to a lesser degree , 5 mg significantly increased the mean ASF slope ( p=0.007 and 0.05 vs placebo ) . There was a significant positive correlation between plasma levels of 311C90 and ASF slope changes . Sumatriptan and lorazepam had little effect , but dexfenfluramine produced a significant ASF slope decrease . 311C90 is able to modify a CNS activity that is modulated by serotonin , i.e. the IDAP . This effect is probably the consequence of its super or lipophilicity compared to sumatriptan and of activation of prejunctional 5HT1B/1D autoreceptors , which lowers central serotonin release and thus the preactivation level of sensory cortices Background : Migraine is frequently associated with nonheadache symptoms before , during , and after the headache . Premonitory symptoms occurring before the attack have not been rigorously studied . Should these symptoms accurately predict headache , there are considerable implication s for the pathophysiology and management of migraine . Methods : Electronic diaries were used in a 3-month multicenter study to record nonheadache symptoms before , during , and after migraine . The authors recruited subjects who reported nonheadache symptoms in at least two of three attacks that they believed predicted headache . Symptoms were entered in the diaries by patient initiation and through prompted entries at r and om times daily . Entries could not be altered retrospectively . Data recorded included nonheadache symptoms occurring during all three phases of the migraine , prediction of the attack from premonitory symptoms , general state of health , and action taken to prevent the headache . Results : One hundred twenty patients were recruited : 97 provided usable data . Patients correctly predicted migraine headaches from 72 % of diary entries with premonitory symptoms . A range of cognitive and physical symptoms was reported at a similar rate through all three phases Output:	The review ed papers collectively support the notion that migraine patients have alterations in serotonergic neurotransmission . Most likely , migraine patients have a low cerebral serotonin level between attacks , which elevates during a migraine attack .
MS21946	*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: Little information is available about the effects of inspiratory muscle training in patients with cystic fibrosis ( CF ) . In this study the effects of inspiratory-threshold loading in patients with CF on strength and endurance of the inspiratory muscles , pulmonary function , exercise capacity , dyspnoea and fatigue were evaluated . Sixteen patients were assigned to one of two groups using the minimization method : eight patients in the training group and eight patients in the control group . The training was performed using an inspiratory-threshold loading device . Patients were instructed to use the threshold trainer 20 min a day , 5 days a week for 6 weeks . Patients in the training group trained at inspiratory threshold loads up to 40 % of maximal static inspiratory pressure ( Pimax ) and patients in the control group got ' sham ' training at a load of 10 % of Pimax . No significant differences were found among the two groups in gender , age , weight , height , pulmonary function , exercise capacity , inspiratory-muscle strength and inspiratory-muscle endurance before starting the training programme . Mean ( SD ) age in the control group was 19 ( 5.5 ) years , mean ( SD ) age in the training group was 17 ( 5.2 ) years . Mean FEV1 in both groups was 70 % predicted , mean inspiratory-muscle strength in both groups was above 100 % predicted . All patients except one , assigned to the training group , completed the programme . After 6 weeks of training , mean inspiratory-muscle endurance ( % Pimax ) in the control group increased from 50 % to 54 % ( P = 0.197 ) ; in the training group mean inspiratory muscle endurance ( % Pimax ) increased from 49 % to 66 % ( P = 0.003 ) . Statistical analysis showed that the change in inspiratory-muscle endurance ( % Pimax ) in the training group was significantly higher than in the control group ( P = 0.012 ) . After training , in the training group there was a tendency of improvement in Pimax with an increase from 105 to 123 % predicted , which just fell short of statistical significance ( P = 0.064 ) . After training no significant differences were found in changes from baseline in pulmonary function , exercise capacity , dyspnoea and fatigue . It is concluded that low-intensity inspiratory-threshold loading at 40 % of Pimax was sufficient to elicit an increased inspiratory-muscle endurance in patients with CF We examined the effects of ventilatory muscle endurance training on resting breathing pattern in 12 C6-C7 traumatic quadriplegics at least 1 year post-injury . All subjects had complete motor loss below the lesion level . Subjects were r and omly assigned to a training ( N = 6 ) , or a control group ( N = 6 ) . Baseline tests included measurement of resting ventilation and breathing pattern using mercury in rubber strain gauges for 20 minutes in a seated position ; maximum inspiratory mouth pressure ( MIP ) at FRC , and sustainable inspiratory mouth pressure for 10 minutes ( SIP ) ; lung volumes , and arterial blood gases ( ABG 's ) . The training protocol consisted of breathing through an inspiratory resistor equivalent to 85 % SIP for 15 minutes twice daily , 5 days a week for 8 weeks . Both trainers and controls attended the lab every 2 weeks for re assessment of MIP and SIP and the inspiratory resistance was increased in the training group as SIP increased . At the end of 8 weeks , baseline tests were repeated . All subjects had normal ABG 's . There was a significant increase in mean MIP and SIP in both the control group ( 30 % ± 19 % and 31 % ± 18 % respectively ) , and in the training group ( 42 % ± 24 % and 78 % ± 49 % respectively ) . Although the absolute values for both MIP and SIP were greater in the training group than in the control group , the differences were not significant . The alterations in resting breathing pattern were also the same in both groups . Mean frequency decreased significantly in the control group ( 20.2/minute to 16.9/minute ) and , while insignificant , the change in frequency in the training group was the same , 19.4/minute to 16.4/minute . Mean tidal volume ( Vt ) increased 18.2 % of baseline Vt in the control group and 17.0 % baseline in the trainers , result ing in no change in minute ventilation . As MIP and SIP increased similarly in both groups , the data from the control and trainers was pooled and timing changes re-evaluated pre- and post- study . A significant decrease in mean Ti/Ttot was observed , while no change in Vt/ Ti was found . We concluded that the testing procedure itself provided the stimulus result ing in a significant increase in MIP and SIP . The addition of training did not increase MIP and SIP further . The increased MIP and SIP result ed in a slower and deeper breathing pattern and a significantly shorter Ti/Ttot in both trainers and control subjects Whether , and to what extent , beta 2-agonists protect against respiratory muscle overloading and breathlessness during bronchoconstriction remains to be defined in patients with asthma . In a double blind placebo-controlled study , 100 micrograms of fenoterol were administered to six stable asthmatics before a bronchial provocation test , performed by inhaling doubling concentrations of histamine from a Devilbiss 646 nebulizer . We recorded breathing pattern ( tidal volume VT , inspiratory time TI , total time of the respiratory cycle TTOT ) , inspiratory capacity ( IC ) , dynamic pleural pressure swing ( Pplsw ) , total lung resistance ( RL ) and FEV1 . VT was expressed both in actual values and as % of IC . Changes in VT ( % IC ) during histamine inhalation reflected changes in dynamic end-inspiratory lung volume ( EILV ) . Pplsw was expressed as % of maximal ( the most negative in sign ) pleural pressure , obtained under control conditions during a sniff manoeuvre ( Pplsn ) . Pplsw ( % Pplsn ) is an index of inspiratory muscle effort . The test ended when the concentration of histamine which caused a decrease in FEV1 of > or = 40 % post-saline was reached . Dyspnoea rating was scored by a modified Borg scale . At the ultimate degree of bronchoconstriction ( UDB ) with histamine : ( i ) decrease in FEV1 was similar after placebo and fenoterol , while increase in RL was lower after fenoterol ( P < 0.005 ) ; ( ii ) VT(%IC ) increased less after fenoterol ( P < 0.027 ) ; ( iii ) increases in Pplsw ( % Pplsn ) was lower after fenoterol ( P < 0.001 ) ; ( iv ) delta Borg ( from saline ) was lower ( P < 0.01 ) after fenoterol ; ( v ) differences in delta Borg , from placebo to fenoterol , related to concurrent changes in VT(%IC ) ( r2 = 0.67 ) . In conclusion , at UDB 100 micrograms of fenoterol produced a beneficial effect on the degree of inspiratory muscle loading and breathlessness , an effect greater than it would be expected from measuring FEV1 alone BACKGROUND Men and women respond differently to asthma . PATIENTS AND METHODS Maximal inspiratory mouth pressure ( P(Imax ) ) , beta(2)-agonist consumption , and perception of dyspnea ( POD ) were measured in 22 women and 22 men with mild persistent-to-moderate asthma . Next , the women were r and omized into two groups : those who received inspiratory muscle training and those who received sham training . The training ended when the P(Imax ) of the training group was equal to that of the male subjects . POD was then measured once again . RESULTS Baseline P(Imax ) was significantly lower ( p < 0.01 ) while POD and mean daily beta(2)-agonist consumption were significantly higher in the female subjects . P(Imax ) reached the level of the male subjects at the end of the 20th week of training . The increase in the P(Imax ) was associated with a statistically significant decrease in mean daily beta(2)-agonist use and in POD to a similar level as in male subjects . CONCLUSIONS POD and mean daily beta(2)-agonist consumption in asthmatic women are significantly higher , and the P(Imax ) significantly lower , than that of their male counterparts . When the P(Imax ) of female subjects following training is equal to that in male subjects , the differences in POD and mean daily beta(2)-agonist consumption disappear BACKGROUND It is well documented that the perception of dyspnea ( POD ) , subjectively reported by patients , is related to the activity and strength of the inspiratory muscles , and influences the use of ' as needed ' beta2-agonists . STUDY OBJECTIVE To investigate the relationship among the increase in inspiratory muscle strength after specific inspiratory muscle training , beta2-agonist consumption and the POD in patients with persistent , mild to moderate asthma . METHODS Inspiratory muscle strength , daily beta2-agonist consumption and the POD were measured in 30 patients with mild to moderate asthma . Patients were then r and omly assigned to two groups : one group received specific inspiratory muscle training until an increase of more than 20 cm H2O was reached , and one group was a control group and received sham training . Inspiratory muscle strength , the POD and daily beta2-agonist consumption were assessed during and after the training period . RESULTS There was no good correlation between the baseline maximal inspiratory pressure and the POD , or between the baseline maximal inspiratory pressure and the mean daily beta2-agonist consumption . However , there was a significant correlation between the POD and the mean daily beta2-agonist consumption . The increase in inspiratory muscle strength after the inspiratory muscle training was closely correlated with the decrease in the POD ( P<0.001 ) and the decrease in beta2-agonist consumption ( P<0.001 ) . CONCLUSIONS The present study shows that , in patients with mild to moderate , persistent asthma , there is a correlation between the POD and the mean daily beta2-agonist consumption . When the inspiratory muscles are strengthened , there is a significant decrease in the POD and in beta2-agonist consumption In patients with asthma , the respiratory muscles have to overcome the increased resistance while they become progressively disadvantaged by hyperinflation . We hypothesized that increasing respiratory muscle strength and endurance with specific inspiratory muscle training ( SIMT ) would result in improvement in asthma symptoms in patients with asthma . Thirty patients with moderate to severe asthma were recruited into 2 groups ; 15 patients received SIMT ( group A ) and 15 patients were assigned to the control group ( group B ) and got sham training in a double-blind group-comparative trial . The training was performed using a threshold inspiratory muscle trainer . Subjects of both groups trained five times a week , each session consisted of 1/2-h training , for six months . Inspiratory muscle strength , as expressed by the PImax at RV , increased significantly , from 84.0 + /- 4.3 to 107.0 + /- 4.8 cm H2O ( p < 0.0001 ) and the respiratory muscle endurance , as expressed by the relationship between Pmpeak and PImax from 67.5 + /- 3.1 percent to 93.1 + /- 1.2 percent ( p < 0.0001 ) , in patients of group A , but not in patients of group B. This improvement was associated with significant improvements compared with baseline for asthma symptoms ( nighttime asthma , p < 0.05 ; morning tightness , p < 0.05 ; daytime asthma , p < 0.01 ; cough , p < 0.005 ) , inhaled B2 usage ( p < 0.05 ) , and the number of hospital ( p < 0.05 ) and sick-leave ( p < 0.05 ) days due to asthma . Five patients were able to stop taking oral/IM corticosteroids while on training and one in the placebo group . We conclude that SIMT , for six months , improves the inspiratory muscle strength and endurance , and results in improvement in asthma symptoms , hospitalizations for asthma , emergency department contact , absence from school or work , and medication consumption in patients with asthma BACKGROUND It has been known for many years that there are variations between asthmatic patients in terms of their perception of breathlessness during airway obstruction . STUDY OBJECTIVE To investigate the relationship between beta(2)-agonist consumption and the score of perception of dyspnea , in mild asthmatics , and the relationship between the effect of specific inspiratory muscle training ( SIMT ) on the score of perception of dyspnea and beta(2)-agonist consumption in " high perceivers . " METHODS Daily beta(2)-agonist consumption was assessed during a 4-week run-in period in 82 patients with mild asthma . Patients with a mean beta(2)-agonist consumption of > 1 puff/d ( " high consumers " ) then were r and omized into two groups : one group of patients received SIMT for 3 months ; the other group of patients was assigned as a control group and received sham training . Inspiratory muscle strength and perception of dyspnea were assessed before patients entered the study , following the 4-week run-in period , and after completing the training period . RESULTS Following the 4-week run-in period , 23 high-consumer patients ( mean [ + /- SEM ] beta(2)-agonist consumption , 2.7 + /- 0.4 puffs/d ) were detected . The mean Borg score during breathing against resistance was significantly higher ( p < 0.05 ) in the patients with high beta(2)-agonist consumption than in the subjects with low mean beta(2)-agonist consumption . Following SIMT , the mean maximal inspiratory pressure increased significantly from 94.1 + /- 5.1 to 109.7 + /- 5.2 cm H(2)O ( Output:	Therefore it is not possible to confirm whether this increase seen with PI(max ) translates into any measurable clinical benefit . REVIEW ER 'S CONCLUSIONS Currently there is insufficient evidence to suggest that inspiratory muscle training provides any clinical benefit to patients with asthma .
MS21947	*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 — Heart failure has an annual mortality rate ranging from 5 % to 75 % . The purpose of the study was to develop and vali date a multivariate risk model to predict 1- , 2- , and 3-year survival in heart failure patients with the use of easily obtainable characteristics relating to clinical status , therapy ( pharmacological as well as devices ) , and laboratory parameters . Methods and Results — The Seattle Heart Failure Model was derived in a cohort of 1125 heart failure patients with the use of a multivariate Cox model . For medications and devices not available in the derivation data base , hazard ratios were estimated from published literature . The model was prospect ively vali date d in 5 additional cohorts totaling 9942 heart failure patients and 17 307 person-years of follow-up . The accuracy of the model was excellent , with predicted versus actual 1-year survival rates of 73.4 % versus 74.3 % in the derivation cohort and 90.5 % versus 88.5 % , 86.5 % versus 86.5 % , 83.8 % versus 83.3 % , 90.9 % versus 91.0 % , and 89.6 % versus 86.7 % in the 5 validation cohorts . For the lowest score , the 2-year survival was 92.8 % compared with 88.7 % , 77.8 % , 58.1 % , 29.5 % , and 10.8 % for scores of 0 , 1 , 2 , 3 , and 4 , respectively . The overall receiver operating characteristic area under the curve was 0.729 ( 95 % CI , 0.714 to 0.744 ) . The model also allowed estimation of the benefit of adding medications or devices to an individual patient 's therapeutic regimen . Conclusions — The Seattle Heart Failure Model provides an accurate estimate of 1- , 2- , and 3-year survival with the use of easily obtained clinical , pharmacological , device , and laboratory characteristics Background — An increase in troponin I soon after high-dose chemotherapy ( HDC ) is a strong predictor of poor cardiological outcome in cancer patients . This finding has important clinical implication s and provides a rationale for the development of prophylactic strategies for preventing cardiotoxicity . Angiotensin-converting enzyme inhibitors slow the progression of left ventricular dysfunction in different clinical setting s , but their role in the prevention of cardiotoxicity has never been investigated . Methods and Results — Of the 473 cancer patients evaluated , 114 ( 72 women ; mean age , 45±12 years ) who showed a troponin I increase soon after HDC were r and omized to receive ( angiotensin-converting enzyme inhibitor group ; 20 mg/d ; n=56 ) or not to receive ( control subjects ; n=58 ) enalapril . Treatment was started 1 month after HDC and continued for 1 year . Cardiological evaluation was performed at baseline and at 1 , 3 , 6 , and 12 months after HDC . The primary end point was an absolute decrease > 10 percent units in left ventricular ejection fraction , with a decline below the normal limit value . A significant reduction in left ventricular ejection fraction and an increase in end-diastolic and end-systolic volumes were observed only in untreated patients . According to the Kaplan-Meier analysis , the incidence of the primary end point was significantly higher in control subjects than in the angiotensin-converting enzyme inhibitor group ( 43 % versus 0 % ; P<0.001 ) . Conclusions — In high-risk , HDC-treated patients , defined by an increased troponin I value , early treatment with enalapril seems to prevent the development of late cardiotoxicity PURPOSE We investigated the incidence of cardiac adverse events in patients with early breast cancer in the Herceptin Adjuvant ( HERA ) trial who were treated with 1 year of trastuzumab after completion of (neo)adjuvant chemotherapy . PATIENTS AND METHODS The HERA trial is a three-group , r and omized trial that compared 1 year or 2 years of trastuzumab with observation in women with human epidermal growth factor receptor-2 ( HER2 ) -positive early breast cancer . Eligible patients had normal left ventricular ejection fraction ( LVEF ; > or= 55 % ) after completion of (neo)adjuvant chemotherapy with or without radiotherapy . Cardiac function was monitored throughout the trial . This analysis considers patients r and omly assigned to 1 year of trastuzumab treatment or observation . RESULTS There were 1,698 patients r and omly assigned to observation and 1,703 r and omly assigned to 1 year of trastuzumab treatment ; 94.1 % of patients had been treated with anthracyclines . The incidence of discontinuation of trastuzumab because of cardiac disorders was low ( 5.1 % ) . At a median follow-up of 3.6 years , the incidence of cardiac end points remained low , though it was higher in the trastuzumab group than in the observation group ( severe CHF , 0.8 % v 0.0 % ; confirmed significant LVEF decreases , 3.6 % v 0.6 % ) In the trastuzumab group , 59 of 73 patients with a cardiac end point reached acute recovery ; of these 59 patients , 52 were considered by the cardiac advisory board ( CAB ) to have a favorable outcome from the cardiac end point . CONCLUSION The incidence of cardiac end points remains low even after longer-term follow-up . The cumulative incidence of any type of cardiac end point increases during the scheduled treatment period of 1 year , but it remains relatively constant thereafter 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 The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy . PATIENTS AND METHODS The Herceptin Adjuvant ( HERA ) trial is a three-group , multicenter , open-label r and omized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2-positive breast cancer . Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction ( LVEF > or = 55 % ) were eligible . A repeat LVEF assessment was performed in case of cardiac dysfunction . RESULTS Data were available for 1,693 patients r and omly assigned to 1 year trastuzumab and 1,693 patients r and omly assigned to observation . The incidence of trastuzumab discontinuation due to cardiac disorders was low ( 4.3 % ) . The incidence of cardiac end points was higher in the trastuzumab group compared with observation ( severe congestive heart failure [ CHF ] , 0.60 % v 0.00 % ; symptomatic CHF , 2.15 % v 0.12 % ; confirmed significant LVEF drops , 3.04 % v 0.53 % ) . Most patients with cardiac dysfunction recovered in fewer than 6 months . Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin ( 287 mg/m(2 ) v 257 mg/m(2 ) ) or epirubicin ( 480 mg/m(2 ) v 422 mg/m(2 ) ) and had a lower screening LVEF and a higher body mass index . CONCLUSION Given the clear benefit in disease-free survival , the low incidence of cardiac adverse events , and the suggestion that cardiac dysfunction might be reversible , adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria BACKGROUND Trastuzumab , a recombinant monoclonal antibody against HER2 , has clinical activity in advanced breast cancer that overexpresses HER2 . We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy . METHODS This international , multicenter , r and omized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy . RESULTS Data were available for 1694 women r and omly assigned to two years of treatment with trastuzumab , 1694 women assigned to one year of trastuzumab , and 1693 women assigned to observation . We report here the results only of treatment with trastuzumab for one year or observation . At the first planned interim analysis ( median follow-up of one year ) , 347 events ( recurrence of breast cancer , contralateral breast cancer , second nonbreast malignant disease , or death ) were observed : 127 events in the trastuzumab group and 220 in the observation group . The unadjusted hazard ratio for an event in the trastuzumab group , as compared with the observation group , was 0.54 ( 95 percent confidence interval , 0.43 to 0.67 ; P<0.0001 by the log-rank test , crossing the interim analysis boundary ) , representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points . Overall survival in the two groups was not significantly different ( 29 deaths with trastuzumab vs. 37 with observation ) . Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab . CONCLUSIONS One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer . ( Clinical Trials.gov number , NCT00045032 . OBJECTIVES The aim of this study was to determine the protective effect of carvedilol in anthracycline (ANT)-induced cardiomyopathy ( CMP ) . BACKGROUND Despite its broad effectiveness , ANT therapy is associated with ANT-induced CMP . Recent animal studies and experimental observations showed that carvedilol prevented development of CMP due to chemotherapeutics . However , there is no placebo-controlled clinical trial concerning prophylactic carvedilol use in preventing ANT-induced CMP . METHODS Patients in whom ANT therapy was planned were r and omized to administration of carvedilol or placebo . We enrolled 25 patients in carvedilol and control groups . In the carvedilol group , 12.5 mg once-daily oral carvedilol was given during 6 months . The patients were evaluated with echocardiography before and after chemotherapy . Left ventricular ejection fraction ( EF ) and systolic and diastolic diameters were calculated . RESULTS At the end of 6 months of follow-up , 1 patient in the carvedilol group and 4 in the control group had died . Control EF was below 50 % in 1 patient in the carvedilol group and in 5 in the control group . The mean EF of the carvedilol group was similar at baseline and control echocardiography ( 70.5 vs. 69.7 , respectively ; p = 0.3 ) , but in the control group the mean EF at control ech Output:	By following these recommendations the incidence of heart failure is reduced to approximately five per cent of treated patients . CONCLUSION In summary , the favourable effects of trastuzumab are convincing , but cardiotoxicity is a significant challenge in treatment .
MS21948	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE The aim of this study was to investigate the effect of time on pharmacokinetic ( PK ) parameters of mycophenolic acid ( MPA ) in the early post-transplant period in kidney recipients . MPA is the active metabolite of mycophenolate mofetil ( MMF ) , which was introduced into clinical practice ten years ago . METHOD Mycophenolate mofetil was co-administered with cyclosporin ( CsA ) in a subgroup of 23 patients and with tacrolimus ( Tac ) in a subgroup of 10 patients . MPA plasma concentration profiles were measured by a vali date d high performance liquid chromatography method 1 week , 2 and 3 months after transplantation . RESULTS Despite a comparable MMF dose , a large inter-patient variability in both MPA area under the curve ( AUC ) from 0 to 12 h ( range 10.03 - 135.4 microg h/mL ) and in predose concentrations ( 0.31 - 6.09 microg/mL ) was observed . Patients with AUC > 35 microg h/mL showed better ( P < 0.1 ) renal function than patients with AUC < 20 microg h/mL ( mean creatinine concentration 1.48 + /- 0.12 vs. 3.35 + /- 0.4 mg/dL respectively ) . The total MPA trough and AUC did not correlate with biochemical parameters : leucocyte cell count and haematocrit . A higher trough level of the metabolite MPA glucuronide ( MPAG ) in the 1 week after transplantation was found when compared with the 3-month level ( mean 150.1 + /- 146.7 ; range 17.1 to 560 vs. 75.8 + /- 40.0 ; range 27.3 to 174.2 microg/mL ) . The concentration of MPA , and MPA AUC values were significantly lower in patients receiving MMF and CsA than those receiving MMF and Tac during all three periods studied ( P < 0.02 ) . The influence of C(0 ) and MPA AUC values on the risk of graft rejection was investigated using receiver operating characteristic ( ROC ) curve analysis . The area under the ROC curve for AUC was 0.847 , whereas that of C(0 ) was 0.632 . CONCLUSIONS The MPA AUC(0 - 12h ) appeared to be the more effective PK parameter for predicting acute rejection . We recommend that routine MPA and MPAG therapeutic drug level monitoring should be an important part of MMF therapy The pharmacokinetics of mycophenolic acid ( MPA ) was studied after oral administration of mycophenolate mofetil ( MMF ) in 8 liver transplant patients . The mean ( + /- SD ) maximum MPA plasma concentration of 10.6 ( + /- 7.5 ) mg/ml was achieved within 0.5 to 5 hours . The mean ( + /- SD ) steady-state area under the plasma concentration versus time curve ( AUC(0 - 12 ) ) was 40 ( + /- 30.9 ) mg/ml/h . The mean ( + /- SD ) half-life was 5.8 ( + /- 3.8 ) hours . There was poor correlation between trough blood concentrations of tacrolimus ( r = -0.004 ) or serum creatinine ( r = 0.689 ) with MPA AUC , while the serum bilirubin concentrations correlated ( r = 0.743 ) well with MPA AUC , suggesting impairment in MPA conjugation in patients with liver dysfunction . The mean ( + /- SD ) ratio of the AUC of mycophenolic acid glucuronide ( MPAG ) to MPA was 64 ( + /- 84 ) , which correlated significantly with serum creatinine ( r = 0.72 ) but not with serum bilirubin concentrations ( r = 0.309 ) , indicating accumulation of MPAG in patients with renal dysfunction . In 7 primary liver transplant patients on the same dose of MMF , the trough plasma concentrations of MPA during the first week of therapy ranged from < 0.3 to 1.5 microg/ml . The MPA concentrations increased by several folds during the next few weeks , which correlates well with increases in serum albumin concentrations . Changes in albumin appear to partially contribute to the variations in the pharmacokinetics of MPA in liver transplant patients BACKGROUND Significant relationships between the mycophenolic acid ( MPA ) area under the concentration-time curve ( AUC(0 - 12h ) ) and the risks for acute rejection and side effects have been reported . We developed a practical method for estimation of MPA AUCs . Regression equations were developed using repeated cross-validation for r and omly chosen subsets , characterized statistically , and verified for acceptable performance . METHODS Twenty-one renal transplant patients receiving 0.5 or 1.0 g of mycophenolate mofetil twice daily and concomitant tacrolimus provided a total of 50 pharmacokinetic profiles . MPA concentrations were measured by a vali date d HPLC method in 12 plasma sample s collected at predose and at 30 and 60 min ; 2 , 3 , 4 , 6 , 8 , 9 , 10 , 11 , and 12 h ; 1 and 2 weeks ; and 3 months after transplantation . Twenty-six 1- , 2- , or 3- sample estimation models were fit ( r(2 ) = 0.341 - 0.862 ) to a r and omly selected subset of the profiles using linear regression and were used to estimate AUC(0 - 12h ) for the profiles not included in the regression fit , comparing those estimates with the corresponding AUC(0 - 12h ) values , calculated with the linear trapezoidal rule , including all 12 timed MPA concentrations . The 3- sample models were constrained to include no sample s past 2 h. RESULTS The model using c(0h ) , c(0.5h ) , and c(2h ) was superior to all other models tested ( r(2 ) = 0.862 ) , minimizing prediction error for the AUC(0 - 12h ) values not included in the fit ( i.e. , the cross-validation error ) . The regression equation for AUC estimation that gave the best performance for this model was : 7.75 + 6.49c(0h ) + 0.76c(0.5h ) + 2.43c(2h ) . When we applied this model to the full data set , 41 of the 50 ( 82 % ) estimated AUC values were within 15 % of the value of AUC(0 - 12h ) calculated using all 12 concentrations . CONCLUSIONS This limited sampling strategy provides an effective approach for estimation of the full MPA AUC(0 - 12h ) in renal transplant patients receiving concomitant tacrolimus therapy Mycophenolate mofetil ( MMF ) is a prodrug immunosuppressant with a high oral bioavailability . Enterohepatic cycling of a glucuronide derivative of MMF contributes substantially to the bioavailability , but is dependent on bacterial deglucuronidation by intestinal flora . This study aims to determine whether an antibiotic regimen with activity against such organisms reduces the bioavailability of MMF by impairing enterohepatic cycling . In a prospect i ve trial , 6 liver transplant recipients were administered MMF and a 21-day antibiotic regimen for selective bowel decontamination ( SBD ) . Time-concentration profiles of the pharmacologically active metabolite , mycophenolic acid ( MPA ) , were obtained during and after the SBD regimen . The bioavailability of MPA was reduced during compared with after the regimen ( 14.5 + /- 3.5 v 21.1 + /- 9.8 mg . h/mL ; P = .07 ) . The most pronounced contribution to this reduction was observed from 6 hours onward ( 2.4 + /- 1.4 v 5.6 + /- 4.4 mg . h/mL ; P < .05 ) . The presence of secondary maxima in the time-concentration profiles of MPA after , but not during , SBD indicates that enterohepatic cycling may be inhibited during SBD and restored afterward . Enterohepatic cycling may contribute 7 % to 54 % ( mean , 29 % ) of the bioavailability of MPA . We conclude that the bioavailability of MMF may be reduced when SBD is used , and the reduction is likely to result from the interruption of enterohepatic cycling . This mechanism should be taken into consideration not only during SBD , but in any clinical setting combining MMF and broad-spectrum antibiotics BACKGROUND Mycophenolate mofetil ( MMF ) is an effective posttransplantation immunosuppressive agent used in combination with cyclosporin A ( CsA ) or tacrolimus ( Tc ) . An increase in plasma mycophenolic acid ( MPA ) has been shown in patients receiving Tc-MMF combination therapy compared with CsA-MMF combination therapy at the same dose of MMF . The aim of this prospect i ve study was to assess the pharmacokinetic/pharmacodynamic ( PK/PD ) relationship for MPA in kidney transplant patients receiving low-dose MMF ( 500 mg twice a day ) in combination with Tc . METHODS Adult kidney transplant recipients ( n = 51 ) were included . MPA-PK profiles ( blood sampling at 0 , 0.5 , 1 , 2 , 4 , 6 , and 12 h after MMF oral dose ) were obtained within the first 2 weeks after transplantation , 3 months after grafting , and at every adverse clinical event [ side effect or acute rejection ( AR ) ] . All patients received Tc , MMF ( 500 mg twice a day ) , and steroids . RESULTS Thirty patients ( 59 % ) had uneventful outcomes , and 21 patients had 33 episodes of MPA-related side effects ; only 3 patients had AR . A total of 78 MPA-PK profiles were obtained . The following PK parameters were increased in the side-effects group compared with the non-side effects group : mean MPA c(min ) , 2.63 + /- 1.58 vs 1.75 + /- 0.82 mg/L ( P = 0.016 ) ; mean c(30 ) , 10.47 + /- 6.27 vs 7.66 + /- 8.95 mg/L ( P = 0.009 ) ; mean c(60 ) , 9.67 + /- 5.42 vs 5.83 + /- 2.6 mg/L ( P = 0.0002 ) ; mean area under the MPA time-concentration curve from 0 to 12 h [ MPA-AUC((0 - 12 ) ) ] , 48.38 + /- 18.5 vs 36.04 + /- 10.82 mg . h/L ( P = 0.0006 ) ; mean dose-normalized MPA-AUC , 0.16 + /- 0.05 vs 0.12 + /- 0.04 ( mg . h/L)/(mg/m(2 ) ) ( P = 0.0015 ) . For the three AR patients , MPA concentrations obtained at the time of AR revealed MPA c(min ) values of 1.86 , 1.76 , and 3.83 mg/L , respectively , and MPA-AUC((0 - 12 ) ) values of 37.7 , 24.9 , and 104.9 mg . h/L. The threshold of toxicity was 3 mg/L ( sensitivity , 38.7 % ; specificity , 91.5 % ) for c(min ) , 8.09 mg/L for maximum MPA concentration during the first hour ( sensitivity , 77.8 % ; specificity , 67.4 % ) , and 37.6 mg . h/L for MPA-AUC((0 - 12 ) ) ( sensitivity , 83.3 % ; specificity , 59.6 % ) . CONCLUSIONS These results demonstrate the relationship between plasma MPA concentrations and toxicity . High c(min ) , c(30 ) , and c(60 ) values as well as AUC((0 - 12 ) ) are associated with increased risk for side effects . These values may have an importance in a routine monitoring program BACKGROUND HPLC is currently the preferred method for accurate measurement of mycophenolic acid ( MPA ) . This study was design ed to vali date the Emit compared with HPLC in relation to clinical outcome measurements . METHODS Pediatric renal-transplant recipients ( n = 50 ) on an immunosuppressive triple regimen consisting of cyclosporin A , prednisone , and mycophenolate mofetil ( 600 mg/m(2 ) twice per day ) were investigated in an open-label prospect i ve study . Pharmacokinetic profiles over 12 h were obtained at 1 week , 3 weeks , 3 months , and 6 months posttransplant . Plasma MPA was measured by both reversed-phase HPLC and the Emit immunoassay . RESULTS There was an association between the risk of acute rejection episodes and low area under the curve values from t(0 ) to t(12h ) ( AUC(0 - 12 ) ) for MPA ( MPA-AUC(0 Output:	RESULTS The majority of studies are retrospective in nature , demonstrating good correlation between the full total MPA area-under-the-curve and the risk of acute rejection , but not toxicity . Free MPA levels may better predict toxicity . Single-point parameters , in particular trough levels , show poor correlation with the risk of acute rejection and toxicity , and in prospect i ve studies do not improve clinical outcomes . Limited sampling strategies using sample s from the first few hours postdose allow good prediction of the full area-under-the-curve , and monitoring using these strategies may improve clinical outcomes .
MS21949	*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 VENTURE-AF is the first prospect i ve r and omized trial of uninterrupted rivaroxaban and vitamin K antagonists ( VKAs ) in patients with non-valvular atrial fibrillation ( NVAF ) undergoing catheter ablation ( CA ) . Methods and results Trial size was administratively set at 250 , the protocol -specified target . Events were independently and blindly adjudicated . We r and omly assigned 248 NVAF patients to uninterrupted rivaroxaban ( 20 mg once-daily ) or to an uninterrupted VKA prior to CA and for 4 weeks afterwards . The primary endpoint was major bleeding events after CA . Secondary endpoints included thromboembolic events ( composite of stroke , systemic embolism , myocardial infa rct ion , and vascular death ) and other bleeding or procedure-attributable events . Patients were 59.5 ± 10 years of age , 71 % male , 74 % paroxysmal AF , and had a CHA2DS2-VASc score of 1.6 . The average total heparin dose used to manage activated clotting time ( ACT ) was slightly higher ( 13 871 vs. 10 964 units ; P < 0.001 ) and the mean ACT level attained slightly lower ( 302 vs. 332 s ; P < 0.001 ) in rivaroxaban and VKA arms , respectively . The incidence of major bleeding was low ( 0.4 % ; 1 major bleeding event ) . Similarly , thromboembolic events were low ( 0.8 % ; 1 ischemic stroke and 1 vascular death ) . All events occurred in the VKA arm and all after CA . The number of any adjudicated events ( 26 vs. 25 ) , any bleeding events ( 21 vs. 18 ) , and any other procedure-attributable events ( 5 vs. 5 ) were similar . Conclusion In patients undergoing CA for AF , the use of uninterrupted oral rivaroxaban was feasible and event rates were similar to those for uninterrupted VKA therapy . Name of the Trial Registry Clinical trials.gov trial registration number is NCT01729871 OBJECTIVES The purpose of this study was to evaluate the feasibility and safety of periprocedural dabigatran during atrial fibrillation ( AF ) ablation . BACKGROUND AF ablation requires optimal periprocedural anticoagulation for minimizing bleeding and thromboembolic complications . The safety and efficacy of dabigatran as a periprocedural anticoagulant for AF ablation are unknown . METHODS We performed a multicenter , observational study from a prospect i ve registry including all consecutive patients undergoing AF ablation in 8 high-volume centers in the United States . All patients receiving dabigatran therapy who underwent AF ablation on periprocedural dabigatran , with the dose held on the morning of the procedure , were matched by age , sex , and type of AF with an equal number of patients undergoing AF ablation with uninterrupted warfarin therapy over the same period . RESULTS A total of 290 patients , including 145 taking periprocedural dabigatran and an equal number of matched patients taking uninterrupted periprocedural warfarin , were included in the study . The mean age was 60 years with 79 % being male and 57 % having paroxysmal AF . Both groups had a similar CHADS(2 ) score , left atrial size , and left ventricular ejection fraction . Three thromboembolic complications ( 2.1 % ) occurred in the dabigatran group compared with none in the warfarin group ( p = 0.25 ) . The dabigatran group had a significantly higher major bleeding rate ( 6 % vs. 1 % ; p = 0.019 ) , total bleeding rate ( 14 % vs. 6 % ; p = 0.031 ) , and composite of bleeding and thromboembolic complications ( 16 % vs. 6 % ; p = 0.009 ) compared with the warfarin group . Dabigatran use was confirmed as an independent predictor of bleeding or thromboembolic complications ( odds ratio : 2.76 , 95 % confidence interval : 1.22 to 6.25 ; p = 0.01 ) on multivariate regression analysis . CONCLUSIONS In patients undergoing AF ablation , periprocedural dabigatran use significantly increases the risk of bleeding or thromboembolic complications compared with uninterrupted warfarin therapy INTRODUCTION Stroke can be a life-threatening complication of atrial fibrillation ( AF ) catheter ablation . Uninterrupted warfarin treatment contributes to minimizing the risk of stroke complications . METHODS AND RESULTS This was a prospect i ve , open-label , r and omized , multicenter study assessing the safety and efficacy of apixaban for the prevention of cerebral thromboembolism complicating AF catheter ablation . Two hundred patients with drug-resistant AF were equally assigned to take either apixaban ( 5 mg or 2.5 mg twice daily ) or warfarin ( target international normalized ratio , 2 - 3 ) for at least 1 month before AF ablation . Neither drug regimen was interrupted throughout the operative period . Diffusion-weighted magnetic resonance imaging was performed for all patients to detect silent cerebral infa rct ion ( SCI ) after the ablation . Primary outcomes were defined as the occurrence of stroke , transient ischemic attack , SCI , or major bleeding that required intervention . The secondary outcome was minor bleeding . The groups did not statistically differ in patients ' background s or procedural parameters . During AF ablation , the apixaban group required administration of more heparin to maintain an activated clotting time > 300 seconds than the warfarin group ( apixaban , 14,000 ± 4,000 units ; warfarin , 9,000 ± 3,000 units ) . Three primary outcome events occurred in each group ( apixaban , 2 SCI and 1 major bleed ; warfarin , 3 SCI , P = 1.00 ) , and 3 and 4 secondary outcome events occurred in the apixaban and warfarin groups ( P = 0.70 ) , respectively . CONCLUSION Apixaban has similar safety and effectiveness to warfarin for the prevention of cerebral thromboembolism during the periprocedural period of AF ablation Background Systemic thromboembolism and bleeding remain the two most common and serious complications of catheter ablation of atrial fibrillation . A variety of periprocedure anticoagulation strategies have been proposed to mitigate these risks . Although operators are now routinely administering dabigatran for anticoagulation in this setting , its relative safety and effectiveness compared to warfarin are unknown . Methods and results A total of 202 patients received dabigatran as part of their periprocedural anticoagulation regimen at the time of initial or redo catheter ablation for symptomatic atrial fibrillation . A comparison group of 202 patients treated with warfarin was r and omly selected from patients undergoing atrial fibrillation ( AF ) ablation during the same time period . AF types were paroxysmal in 223 patients , persistent in 158 patients , and longst and ing persistent in 13 patients . Mean age was 60.0 ± 10.5 years , 55 % had a history of hypertension , and mean CHADS-VASc score was 1.7 ± 1.3 . “ Continuous ” warfarin or dabigatran was administered in 80 and 32 % of patients , respectively . Time to first dose of dabigatran post-procedure was 12.2 ± 10.3 h. Two dabigatran and no warfarin-treated patients had systemic thromboembolism ( p = NS ) ; five dabigatran and three warfarin-treated patients had bleeding complications ( p = NS , combined endpoint p = 0.116 ) . One dabigatran patient had severe pericardial bleeding ( 3 L blood loss ) . Conclusions In a retrospective pilot trial comparing the risks of systemic thromboembolism or bleeding complications in patients treated with warfarin or dabigatran anticoagulation , the outcomes were similar . A prospect i ve trial is warranted OBJECTIVES The purpose of this study was to evaluate the feasibility and safety of uninterrupted rivaroxaban therapy during atrial fibrillation ( AF ) ablation . BACKGROUND Optimal periprocedural anticoagulation strategy is essential for minimizing bleeding and thromboembolic complications during and after AF ablation . The safety and efficacy of uninterrupted rivaroxaban therapy as a periprocedural anticoagulant for AF ablation are unknown . METHODS We performed a multicenter , observational , prospect i ve study of a registry of patients undergoing AF ablation in 8 centers in North America . Patients taking uninterrupted periprocedural rivaroxaban were matched by age , sex , and type of AF with an equal number of patients taking uninterrupted warfarin therapy who were undergoing AF ablation during the same period . RESULTS A total of 642 patients were included in the study , with 321 in each group . Mean age was 63 ± 10 years , with 442 ( 69 % ) males and 328 ( 51 % ) patients with paroxysmal AF equally distributed between the 2 groups . Patients in the warfarin group had a slightly higher mean HAS- BLED ( hypertension , abnormal renal/liver function , stroke , bleeding history or predisposition , labile international normalized ratio , elderly , drugs/alcohol concomitantly ) score ( 1.70 ± 1.0 vs. 1.47 ± 0.9 , respectively ; p = 0.032 ) . Bleeding and embolic complications occurred in 47 ( 7.3 % ) and 2 ( 0.3 % ) patients ( both had transient ischemic attacks ) respectively . There were no differences in the number of major bleeding complications ( 5 [ 1.6 % ] vs. 7 [ 1.9 % ] , respectively ; p = 0.772 ) , minor bleeding complications ( 16 [ 5.0 % ] vs. 19 [ 5.9 % ] , respectively ; p = 0.602 ) , or embolic complications ( 1 [ 0.3 % ] vs. 1 [ 0.3 % ] , respectively ; p = 1.0 ) between the rivaroxaban and warfarin groups in the first 30 days . CONCLUSIONS Uninterrupted rivaroxaban therapy appears to be as safe and efficacious in preventing bleeding and thromboembolic events in patients undergoing AF ablation as uninterrupted warfarin therapy Advances in antithrombotic therapy , along with an early invasive strategy , have reduced the incidence of recurrent ischemic events and death in patients with acute coronary syndromes ( ACS ; unstable angina , non – ST-segment – elevation myocardial infa rct ion [ MI ] , and ST-segment – elevation MI).1,–,4 However , the combination of multiple pharmacotherapies , including aspirin , platelet P2Y12 inhibitors , heparin plus glycoprotein IIb/IIIa inhibitors , direct thrombin inhibitors , and the increasing use of invasive procedures , has also been associated with an increased risk of bleeding . Editorial see p 2664 Bleeding complications have been associated with an increased risk of subsequent adverse outcomes , including MI , stroke , stent thrombosis , and death , in patients with ACS and in those undergoing percutaneous coronary intervention (PCI),5,–,10 as well as in the long-term antithrombotic setting .11,12 Thus , balancing the anti-ischemic benefits against the bleeding risk of antithrombotic agents and interventions is of paramount importance in assessing new therapies and in managing patients . Prior r and omized trials comparing antithrombotic agents suggest that a reduction in bleeding events is associated with improved survival.13,14 Because prevention of major bleeding may represent an important step in improving outcomes by balancing safety and efficacy in the contemporary treatment of ACS , bleeding events have been systematic ally identified as a crucial end point for the assessment of the safety of drugs during the course of r and omized clinical trials , and are an important aspect of the evaluation of new devices and interventional therapies.15 Unlike ischemic clinical events ( eg , cardiac death , MI , stent thrombosis ) , for which there is now general consensus on end-point definitions,16,17 there is substantial heterogeneity among the many bleeding definitions currently in use . Lack of st and ardization makes it difficult to optimally organize key clinical trial processes such as adjudication , and even more difficult to interpret relative Purpose Left atrial catheter ablation for patients with atrial fibrillation ( AF ) requires periprocedural anticoagulation to minimize thromboembolic complications . High rates of major bleeding complications using dabigatran etexilate for periprocedural anticoagulation have been reported , raising concerns regarding its safety during left atrial catheter ablation . We sought to evaluate the safety and efficacy of a dabigatran use strategy versus warfarin , at a single high-volume AF ablation center . Methods We performed a retrospective analysis on consecutive patients undergoing left atrial ablation at V and erbilt Medical Center from January 2011 through August 2012 with a minimum follow-up of 3 months . Patient cohorts were divided into two groups , those utilizing dabigatran etexilate pre- and post-ablation and those undergoing ablation on Output:	Conclusion An uninterrupted DOACs strategy for CA of NVAF appears to be as safe as uninterrupted VKA without a significantly increased risk of minor or major bleeding events . There was a trend favouring DOACs in terms of major bleeding .
MS21950	*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 —Certain proton pump inhibitors ( PPIs ) interfere with clopidogrel metabolism , potentially attenuating P2Y12 receptor inhibition . Previous observational and r and omized trials report conflicting results regarding the clinical significance of this pharmacological interaction . We examined the interaction between concomitant administration of PPI and clopidogrel on platelet reactivity and clinical outcomes in the large-scale , prospect i ve Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents study . Methods and Results —On-treatment P2Y12 platelet reactivity testing was performed using the VerifyNow assay after clopidogrel loading and successful drug-eluting stent implantation at 11 sites in the United States and Germany . PPIs were prescribed at the discretion of treating physicians ; patients were followed for 2 years . High platelet reactivity was defined as P2Y12 reactivity units > 208 . Of 8582 enrolled patients , 2697 ( 31.4 % ) were taking a PPI at the time of coronary intervention . After adjustment for differences in baseline characteristics , PPI use was independently associated with high platelet reactivity ( odds ratio , 1.38 : 95 % confidence interval , 1.25–1.52 , P=0.0001 ) . A total of 2162 ( 25.2 % ) patients were prescribed a PPI at hospital discharge . In a propensity-adjusted multivariable analysis , discharge PPI use was independently associated with increased risk for postdischarge major adverse cardiac events ( cardiac death , myocardial infa rct ion , or ischemia-driven target lesion revascularization ) at 2-year follow-up ( hazard ratio , 1.21 ; 95 % confidence interval , 1.04–1.42 , P=0.02 ) . Conclusions —In patients treated with clopidogrel after successful drug-eluting stents implantation , the concomitant administration of PPI was associated with high platelet reactivity and a greater rate of adverse outcomes during long-term follow-up . Additional studies are warranted to determine the risk – benefit ratio of PPIs in patients with drug-eluting stents treated with clopidogrel . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00433966 BACKGROUND Omeprazole , usually used in the antiplatelet therapy during percutaneous coronary intervention ( PCI ) in acute coronary syndrome ( ACS ) , has been reported to increase ischemic events in retrospective studies . However , other clinical trials gave paradoxical results . The aim of this study was to assess the effects of omeprazole on clopidogrel efficacy and clinical events . METHODS All patients ( n = 172 ) received aspirin ( loading dose 300 mg and maintenance dose 100 mg/d ) and clopidogrel ( loading dose 600 mg and maintenance dose 75 mg/d ) during the therapy . They were r and omized to receive omeprazole ( 20 mg/d ) or placebo for 30 days . Residual platelet activities in the adenosine 5'-diphosphate ( ADP ) pathway were detected on the fifth day after PCI with thrombelastography (TEG)-mapping . The clinical events were recorded after one month . RESULTS According to the five levels of platelet activities , the frequency distributions of the inhibition rates were significantly different ( P = 0.0062 ) . However , no significant change was seen in the distribution among the highest or the lowest inhibiting levels ( > 95 % and < 30 % inhibition rate ) . And there were no significant differences ( P > 0.05 ) in events incidence , while gastro-intestinal bleeding decreased in co-administration of omeprazole . CONCLUSIONS Omeprazole significantly blunts clopidogrel efficacy while not exacerbates ischemic events in ACS undergoing PCI . Omeprazole even can decrease gastro-intestinal bleeding in those patients Background — The clinical significance of the interaction between clopidogrel and proton pump inhibitors ( PPIs ) remains unclear . Methods and Results — We examined the relationship between PPI use and 1-year cardiovascular events ( cardiovascular death , myocardial infa rct ion , or stroke ) in patients with acute coronary syndrome r and omized to clopidogrel or ticagrelor in a prespecified , nonr and omized subgroup analysis of the Platelet Inhibition and Patient Outcomes ( PLATO ) trial . The primary end point rates were higher for individuals on a PPI ( n=6539 ) compared with those not on a PPI ( n=12 060 ) at r and omization in both the clopidogrel ( 13.0 % versus 10.9 % ; adjusted hazard ratio [ HR ] , 1.20 ; 95 % confidence interval [ CI ] , 1.04–1.38 ) and ticagrelor ( 11.0 % versus 9.2 % ; HR , 1.24 ; 95 % CI , 1.07–1.45 ) groups . Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI ( PPI versus non-PPI gastrointestinal treatment : clopidogrel , HR , 0.98 ; 95 % CI , 0.79–1.23 ; ticagrelor , HR , 0.89 ; 95 % CI , 0.73–1.10 ) . In contrast , patients on no gastric therapy had a significantly lower primary end point rate ( PPI versus no gastrointestinal treatment : clopidogrel , HR , 1.29 ; 95 % CI , 1.12–1.49 ; ticagrelor , HR , 1.30 ; 95 % CI , 1.14–1.49 ) . Conclusions — The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel . However , a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment . Therefore , in the PLATO trial , the association between PPI use and adverse events may be due to confounding , with PPI use more of a marker for , than a cause of , higher rates of cardiovascular events . Clinical Trial Registration — http://www . clinical trials.gov . Unique identifier : NCT00391872 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 BACKGROUND It remains unclear whether concomitant use of omeprazole attenuates platelet function as compared with that of famotidine in patients with acute coronary syndromes ( ACS ) who receive clopidogrel . METHODS AND RESULTS In this prospect i ve study , 130 ACS patients treated with aspirin and clopidogrel who underwent stent implantation were r and omly assigned to receive a Japanese st and ard dose of omeprazole 10 mg daily or famotidine 20 mg daily for at least 4 weeks . Between 14 and 28 days after enrollment , there was no significant difference in the platelet reactivity index ( PRI ) measured with vasodilator-stimulated phosphoprotein phosphorylation assay between the omeprazole group ( n=65 ) and famotidine group ( n=65 ) ( 55±17 % vs. 51±19 % ; P=0.26 ) . The cumulative rate of adverse cardiovascular events at 12 months was similar in the groups ( 13 % vs. 17 % ; P=0.81 ) . The PRI was similar ( 54.9±17.9 % vs. 54.0±17.8 % ; P=0.83 ) in the omeprazole group ( n=33 ) and the famotidine group ( n=39 ) among patients with ST-elevation myocardial infa rct ion ( STEMI ) . However , there was a trend toward a higher PRI ( 55.2±15.9 % vs. 46.4±19.4 % ; P=0.06 ) in the omeprazole group ( n=32 ) as compared with the famotidine group ( n=26 ) among patients without persistent ST-segment elevation ACS . CONCLUSIONS As compared with famotidine , concomitant use of low-dose omeprazole does not significantly attenuate the antiplatelet effects of clopidogrel in patients with ACS , especially in those with STEMI BACKGROUND Gastrointestinal complications are an important problem of antithrombotic therapy . Proton-pump inhibitors ( PPIs ) are believed to decrease the risk of such complications , though no r and omized trial has proved this in patients receiving dual antiplatelet therapy . Recently , concerns have been raised about the potential for PPIs to blunt the efficacy of clopidogrel . METHODS We r and omly assigned patients with an indication for dual antiplatelet therapy to receive clopidogrel in combination with either omeprazole or placebo , in addition to aspirin . The primary gastrointestinal end point was a composite of overt or occult bleeding , symptomatic gastroduodenal ulcers or erosions , obstruction , or perforation . The primary cardiovascular end point was a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , revascularization , or stroke . The trial was terminated prematurely when the sponsor lost financing . RESULTS We planned to enroll about 5000 patients ; a total of 3873 were r and omly assigned and 3761 were included in analyses . In all , 51 patients had a gastrointestinal event ; the event rate was 1.1 % with omeprazole and 2.9 % with placebo at 180 days ( hazard ratio with omeprazole , 0.34 , 95 % confidence interval [ CI ] , 0.18 to 0.63 ; P<0.001 ) . The rate of overt upper gastrointestinal bleeding was also reduced with omeprazole as compared with placebo ( hazard ratio , 0.13 ; 95 % CI , 0.03 to 0.56 ; P = 0.001 ) . A total of 109 patients had a cardiovascular event , with event rates of 4.9 % with omeprazole and 5.7 % with placebo ( hazard ratio with omeprazole , 0.99 ; 95 % CI , 0.68 to 1.44 ; P = 0.96 ) ; high-risk subgroups did not show significant heterogeneity . The two groups did not differ significantly in the rate of serious adverse events , though the risk of diarrhea was increased with omeprazole . CONCLUSIONS Among patients receiving aspirin and clopidogrel , prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding . There was no apparent cardiovascular interaction between clopidogrel and omeprazole , but our results do not rule out a clinical ly meaningful difference in cardiovascular events due to use of a PPI . ( Funded by Cogentus Pharmaceuticals ; Clinical Trials.gov number , NCT00557921 . ) BACKGROUND Proton pump inhibitors ( PPIs ) are frequently prescribed in combination with clopidogrel , but conflicting data exist as to whether PPIs diminish the efficacy of clopidogrel . We assessed the association between PPI use and clinical outcomes for patients treated with percutaneous coronary intervention ( PCI ) and dual-antiplatelet therapy ( DAPT ) with clopidogrel plus aspirin . METHODS AND RESULTS In the PRODIGY trial , 1,970 patients were r and omized to 6- or 24-month DAPT at 30 days from index procedure . Among them , 738 patients ( 37.5 % ) received PPI ( mainly lansoprazole ; 90.1 % ) at the time of r and omization . Proton pump inhibitor users were older , were most likely to be woman , had a lower creatinine clearance , presented more frequently with acute coronary syndrome , and had a higher CRUSADE bleeding score . After adjustment , the primary efficacy end point ( composite of all-cause death , myocardial infa rct ion , and cerebrovascular accident ) was similar between no PPI and PPI users ( 9.2 % vs 11.5 % , adjusted hazard ratio [ HR ] 1.051 , 95 % CI 0.788 - 1.400 , P = .736 ) . Bleeding rates did not differ between the 2 groups ( Bleeding Academic Research Consortium type 2 , 3 , or 5 : adjusted HR 0.996 , 95 % CI 0.672 - 1.474 , P = .980 ) . Net clinical adverse events were also similar in no PPI and PPI patients ( 12.9 % vs 14.9 % , adjusted HR 0.99 , 95 % CI 0.772 - 1.268 , P = .93 ) . Output:	Conclusion : Concomitant use of PPIs and clopidogrel has been proved not to be associated with elevated cardiovascular risks according to RCTs .
MS21951	*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 Screen-based activities , such as watching television ( TV ) , playing video games , and using computers , are common sedentary behaviors among young people and have been linked with increased energy intake and overweight . Previous home-based sedentary behaviour interventions have been limited by focusing primarily on the child , small sample sizes , and short follow-up periods . The SWITCH ( Screen-Time Weight-loss Intervention Targeting Children at Home ) study aim ed to determine the effect of a home-based , family-delivered intervention to reduce screen-based sedentary behaviour on body composition , sedentary behaviour , physical activity , and diet over 24 weeks in overweight and obese children . Methods A two-arm , parallel , r and omized controlled trial was conducted . Children and their primary caregiver living in Auckl and , New Zeal and were recruited via schools , community centres , and word of mouth . The intervention , delivered over 20 weeks , consisted of a face-to-face meeting with the parent/caregiver and the child to deliver intervention content , which focused on training and educating them to use a wide range of strategies design ed to reduce their child ’s screen time . Families were given Time Machine TV monitoring devices to assist with allocating screen time , activity packages to promote alternative activities , online support via a website , and monthly newsletters . Control participants were given the intervention material on completion of follow-up . The primary outcome was change in children ’s BMI z-score from baseline to 24 weeks . Results Children ( n = 251 ) aged 9 - 12 years and their primary caregiver were r and omized to receive the SWITCH intervention ( n = 127 ) or no intervention ( controls ; n = 124 ) . There was no significant difference in change of z BMI between the intervention and control groups , although a favorable trend was observed ( -0.016 ; 95 % CI : -0.084 , 0.051 ; p = 0.64 ) . There were also no significant differences on secondary outcomes , except for a trend towards increased children ’s moderate intensity physical activity in the intervention group ( 24.3 min/d ; 95 % CI : -0.94 , 49.51 ; p = 0.06 ) . Conclusions A home-based , family-delivered intervention to reduce all leisure-time screen use had no significant effect on screen-time or on BMI at 24 weeks in overweight and obese children aged 9 - 12 years . Trial registration Australian New Zeal and Clinical Trials RegistryWebsite : http://www.anzctr.org.auTrial registration number : BACKGROUND AND OBJECTIVE : Clinic-based programs for childhood obesity are not available to a large proportion of the population . The purpose of this study was to evaluate the efficacy of a guided self-help treatment of pediatric obesity ( GSH-PO ) compared with a delayed treatment control and to evaluate the impact of GSH-PO 6-months posttreatment . METHODS : Fifty overweight or obese 8- to 12-year-old children and their parents were r and omly assigned to immediate treatment or to delayed treatment . The GSH-PO includes 12 visits over 5 months and addresses key components included in more intensive clinic-based programs . Children and parents in the immediate treatment arm were assessed at time 1 ( T1 ) , participated in GSH-PO between T1 and T2 , and completed their 6-month posttreatment assessment at T3 . Children and parents in the delayed treatment arm were assessed at T1 , participated in GSH-PO between T2 and T3 , and completed their 6-month posttreatment assessment at T4 . The main outcome measures were BMI , BMI z score , and percentage overweight ( % OW ) . RESULTS : Children in the immediate treatment GSH-PO arm decreased their BMI significantly more than did the delayed treatment arm ( BMI group × time = −1.39 ; P < .001 ) . Similar results were found for BMI z score and % OW . At the 6-month posttreatment assessment , changes result ing from GSH-PO were maintained for BMI z score and % OW but not BMI ( BMI time effect = −0.06 , not significant ; BMI z score time effect = −0.10 , P < .001 ; % OW time effect = −4.86 , P < .05 ) . CONCLUSIONS : The GSH-PO showed initial efficacy in decreasing BMI for children in this study . Additional efficacy and translational studies are needed to additionally evaluate GSH-PO OBJECTIVE Maintaining weight loss results in childhood obesity treatment is difficult to achieve . Self-management techniques such as self-monitoring are associated with increased weight loss and maintenance . This study analyzes whether self-monitoring of lifestyle behaviours through a short message service maintenance treatment ( SMSMT ) via mobile phones with personalized feedback positively effects weight , lifestyle behaviours and psychological well-being in obese children . METHODS After 3 months of behavioural lifestyle treatment , 141 overweight and obese children ( 7 - 12 years ) were r and omly assigned to an intervention group receiving SMSMT for 9 months ( n = 73 ) or to the control group ( n = 68 ) . The intervention group sent weekly self-monitoring data on exercise and eating behaviour and their mood via mobile phones . In return , they received tailored feedback messages . Primary treatment outcomes were weight , eating behaviour and psychological well-being , i.e. competence , self-esteem and quality of life . Secondary outcome was adherence to the SMSMT . Data were analyzed with mixed modelling . RESULTS SMSMT did not improve treatment outcomes . Controls gained temporarily in physical health scores ( P = 0.01 ) . SMSMT completers sent on average every 2 weeks an SMS . Children who had greater weight loss during the first 3 months of lifestyle treatment sent more SMSs ( P = 0.04 ) . CONCLUSIONS We did not find a positive effect of SMSMT on weight , eating behaviour or psychological well-being in obese children . SMSMT seems to be a feasible method of treatment delivery . Future research should study variations of SMSMT to investigate how SMSMT can be more effective OBJECTIVES . Television viewing and physical inactivity increase the risk of obesity in youth . Thus , identifying new interventions that increase physical activity and reduce television viewing would be helpful in the prevention and treatment of pediatric obesity . This study evaluated the effects of open-loop feedback plus reinforcement versus open-loop feedback alone on physical activity , targeted sedentary behavior , body composition , and energy intake in youth . METHODS . Thirty overweight or obese 8- to 12-year-old children were r and omly assigned to an intervention ( n = 14 ) or control group ( n = 16 ) . Participants wore accelerometers every day for 8 weeks and attended biweekly meetings to download the activity monitors . For children in the open-loop feedback plus reinforcement ( intervention ) group , accumulating 400 counts of physical activity on pedometers earned 1 hour of television/VCR/DVD time , which was controlled by a Token TV electronic device . Open-loop feedback control subjects wore activity monitors but had free access to targeted sedentary behavior . RESULTS . Compared with controls , the open-loop feedback plus reinforcement group demonstrated significantly greater increases in daily physical activity counts ( + 65 % vs + 16 % ) and minutes per day of moderate-to-vigorous physical activity ( + 9.4 vs + 0.3 ) and greater reductions in minutes per day spent in television viewing ( −116.1 vs + 14.3 ) . The intervention group also showed more favorable changes in body composition , dietary fat intake , and energy intake from snacks compared with controls . Reductions in sedentary behavior were directly related to reductions in BMI , fat intake , snack intake , and snack intake while watching television . CONCLUSIONS . Providing feedback of physical activity in combination with reinforcing physical activity with sedentary behavior is a simple method of modifying the home environment that may play an important role in treating and preventing child obesity Objective : The aim of the study was to compare the efficacy of group treatment stressing a health-promoting lifestyle with routine counseling in the treatment of childhood obesity . Design and subjects : Seventy obese children ( weight for height 115–182 % ) aged 7–9 years were r and omized either to routine counseling ( two appointments for children ) or to family-based group treatment ( 15 separate sessions for parents and children ) . These sessions included nutrition education , physical activity education and behavioral therapy . Outcome measures : Children 's weights and heights were measured at baseline , after the 6-month intervention and after the 6-month follow-up . The change of weight for height based on Finnish growth charts was used as the primary , and changes in body mass index ( BMI ) and BMI st and ard deviation scores ( BMI -SDS ) as secondary outcome measures . Results : Children attending the group treatment lost more weight for height ( 6.8 % ) than children receiving routine counseling ( 1.8 % ) ( P=0.001 ) . The difference was significant when the data were analyzed in four groups by the cut-off limits of 0 , −5 and −10 % for the change in weight for height . The respective decreases in BMI were 0.8 vs 0.0 ( P=0.003 ) and in BMI -SDS 0.3 vs 0.2 ( P=0.022 ) . The results remained similar in adjusted analyses . Both group and routine programs were feasible with a high , 87–99 % , participation rate in sessions and appointments and very low , 3 % or less , attrition rate from the programs . Six months after the intervention , beneficial effects were partly lost , but for changes in weight for height and BMI , the differences between the two treatment programs still were significant , and for BMI -SDS , there was a trend . Conclusions : Family-based group treatment that stresses a health-promoting lifestyle and is given separately for parents and children , offers an effective mode of therapy to treat obese school-aged children The purpose of this study was to assess the effects of a six-months ’ nutrition program , delivered and taught by classroom teachers with in-service nutrition training , on the prevention of overweight and obesity among children in grade s 1 to 4 . In this r and omized trial , four hundred and sixty four children from seven elementary schools were allocated to a nutrition educational program delivered by their own teachers . Intervened teachers had 12 sessions of three hours each with the research ers throughout six months , according to the topics nutrition and healthy eating , the importance of drinking water and healthy cooking activities . After each session , teachers were encouraged to develop activities in class focused on the learned topics . Sociodemographic , anthropometric , dietary , and physical activity assessment s were performed at baseline and at the end of the intervention . In the intervention group the increase in Body Mass Index ( BMI ) z-score was significantly lower than in the control group ( p = 0.009 ) ; fewer proportion of children became overweight in the intervened group compared with the control ( 5.6 % vs. 18.4 % ; p = 0.037 ) . Our study provides further support to decrease the overweight epidemic , involving classroom teachers in a training program and making them dedicated interventionists A strategy is needed on how to treat the growing number of obese children with the limited re sources available . We compared the long-term ( 24 months ) effectiveness of therapist-led groups ( TLG ) v. self-help groups ( SHG ) for parents on changes in children 's adiposity and dietary intake . The study included ninety-nine children ( forty-eight girls ) who were referred to obesity treatment ( 7–12 years , BMI z-scores ≥ 2 , attendance of at least one parent ) . Parents ( ninety-one mothers , fifty-four fathers ) were r and omised to TLG aim ed at increasing parents ' competence to accomplish lifestyle changes ( n 47 ) , or SHG ( n 52 ) , both with fifteen sessions . All children participated in children 's groups , and all families attended individual counselling by a clinical dietitian and physiotherapist . Percentage of body fat ( BF ) was measured by dual-energy X-ray absorptiometry , BMI z-score was calculated by international reference values and dietary intake was calculated from 4 d estimated food records at baseline and after 6 and 24 months . No significant between-group differences were detected in the children 's changes in adiposity or dietary intake after 6 and 24 months . BF , BMI z-scores and energy intake were significantly decreased after 6 months ( P < 0·05 ) in both intervention groups , and this persisted throughout 24 months without compromising the diet macronutrient composition . In conclusion , the TLG and SHG intervention groups appear to be equally effective in improving long-term adiposity and dietary intake in obese children . Further research should be performed to clarify whether the SHG should be preferred to parental group treatment for similar children with obesity OBJECTIVE : We evaluated the efficacy of family-based , behavioral weight control in the management of severe pediatric obesity . METHODS : Participants were 192 children 8.0 to 12.0 years of age ( mean ± SD : 10.2 ± 1.2 years ) . The average BMI percentile for age and gender was 99.18 ( SD : 0.72 ) . Families were assigned r and omly to the intervention or usual care . Assessment s were conducted at baseline , 6 months , 12 months , and 18 months . The primary outcome was percent overweight ( percent over the median BMI for age and gender ) . Changes in blood pressure , body composition , waist circumference , and health-related quality of life also were evaluated . Finally , we examined factors associated with changes in child percent overweight , particularly session attendance . RESULTS : Intervention was associated with significant decreases in child percent overweight , relative to usual care , at 6 months . Intent-to-treat analyses documented that intervention was associated with a 7. Output:	Most interventions incorporated lifestyle changes and behavioural strategies such as coping and problem solving skills with family involvement . The meta-analyses did not show significant effects of the intervention in reducing weight related outcomes when compared with controls . Meta-analyses of the selected studies did not show significant effects of the interventions on weight related outcomes among overweight and obese schoolchildren when compared with controls .
MS21952	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIM To assess the efficacy and safety of a compound containing alginic acid plus antacid ( Topaal ) compared to equal-strength antacid ( Nacid ) in patients with endoscopy-negative reflux disease ( ENRD ) . METHODS A total of 121 patients with ENRD were r and omized to receive Topaal ( 65 patients ) or Nacid ( 56 patients ) for 6 weeks , with a consultation every 3 weeks . The primary end-point assessment was the change in the severity of heartburn as evaluated using a visual analog scale ( VAS ) at 6 weeks . The secondary end-point assessment s were the VAS at 3 weeks , the change of frequency of the reflux symptom , the change of quality of life and the adverse effects . RESULTS Demographics of r and omized subjects in each treatment group were comparable except that the Topaal group included more males . The baseline characteristics between the groups were similar . After 6 weeks of treatment , the reduction of VAS of heartburn was more prominent in the Topaal group ( -6.29 cm vs -4.11 cm ) . At the 3rd week , Topaal group showed greater reduction of VAS for heartburn ( P=0.0016 ) , regurgitation ( P=0.0006 ) , vomiting ( P=0.0373 ) , and belching ( P<0.0001 ) . The patients of the Topaal group had lower frequency of heartburn ( P=0.0015 ) and pain ( P=0.0163 ) at the end of the 6-week treatment period . From the doctor 's point of view , the Topaal group also showed significant reduction in the severity of heartburn ( P=0.0020 ) , regurgitation ( P=0.0081 ) , vomiting ( P=0.0182 ) , and belching ( P=0.0018 ) at the end of the treatment . The improvement of the quality of life was more remarkable in the Topaal group at the end of the 6-week treatment period ( P<0.0001 ) . For the adverse effect , there was no difference in both the groups . CONCLUSION Topaal is more effective than Nacid for the treatment of symptoms presented by patients with ENRD Abstract Three r and omised groups of 20 patients with gastro-œsophageal reflux were studied using 15-hour recordings of lower œsophageal pH , before and after two weeks ' treatment , either with an alginate/antacid compound ( ' Gaviscon ' ) , antacids alone , or a placebo tablet . Significant reduction in the number of reflux episodes and percentage time during which the lower œsophageal pH was acid was noted in the gaviscon group after treatment , whereas no significant changes occurred in the other two groups . Symptoms reported by patients during the second test were fewer after gaviscon treatment than after antacid alone The aims of the present study were to compare effects of sodium alginate and the antacid magaldrate anhydrous in adults with gastroesophageal reflux ( GOR ) symptoms . Patients with heartburn and /or acid regurgitation for at least 3 days in the week before the study started ( n=203 ) were r and omized to receive a single dose of sodium alginate or magaldrate anhydrous at the onset of symptoms during a 3-day run-in period . Patients with symptoms during the run-in ( n=191 ) were rer and omized to receive a 14-day treatment with either drug given as four daily doses . A speed of action ≤30 min was significantly more frequent among patients in the alginate group ( 49.4 % vs. 40.4 % ; P=0.0074 ) . A trend toward a more prolonged duration of action ( median : 16.5 vs. 12.7 hr ) and a greater sum of the symptom intensity difference ( median : 40.0 vs. 31.0 ) was observed in the sodium alginate group . Total disappearance of symptoms was reported in 81.6 % and 73.9 % of patients in the sodium alginate group and magaldrate group , respectively . We conclude that sodium alginate was faster than magaldrate in relieving GRO symptoms and showed a tendency toward a more prolonged duration of action and a higher level of efficacy Background Medical management of GERD mainly uses proton pump inhibitors . Alginates also have proven efficacy . The aim of this trial was to compare short-term efficacy of an alginate ( Gaviscon ® , 4 × 10 mL/day ) and omeprazole ( 20 mg/day ) on GERD symptoms in general practice . Methods A 14-day multicentre r and omised double-blind double-dummy non-inferiority trial compared Gaviscon ® ( 4 × 10 mL/day ) and omeprazole ( 20 mg/day ) in patients with 2 - 6 day heartburn episodes weekly without alarm signals . The primary outcome was the mean time to onset of the first 24-h heartburn-free period after initial dosing . Secondary outcomes were the proportion of patients without heartburn by D7 , pain relief by D7 , and reduction in pain intensity by D7 and D14 . Results 278 patients were recruited ; 120 were included in the Gaviscon ® group and 121 in the omeprazole group for the per protocol non-inferiority analysis . The mean time to onset of the first 24-h heartburn-free period after initial dosing was 2.0 ( ± 2.2 ) days for Gaviscon ® and 2.0 ( ± 2.3 ) days for omeprazole ( p = 0.93 ) ; mean intergroup difference was 0.01 ± 1.55 days ( 95 % CI = -0.41 to 0.43 ) : i.e. , less than the lower limit of the 95 % CI of -0.5 days predetermined to demonstrate non-inferiority . The mean number of heartburn-free days by D7 was significantly greater in the omeprazole group : 3.7 ± 2.3 days vs. 3.1 ± 2.1 ( p = 0.02 ) . On D7 , overall quality of pain relief was slightly in favour of omeprazole ( p = 0.049 ) . There was no significant difference in the reduction in pain intensity between groups by D7 ( p = 0.11 ) or D14 ( p = 0.08 ) . Tolerance and safety were good and comparable in both groups . Conclusion Gaviscon ® was non-inferior to omeprazole in achieving a 24-h heartburn-free period in moderate episodic heartburn , and is a relevant effective alternative treatment in moderate GERD in primary care . Trial registration IS RCT N62203233 Many patients who present with dyspepsia are prescribed antacid/alginates as their first line and often mainstay therapy . This multicentre study was design ed to assess whether early introduction of acid inhibition is an effective strategy in dyspepsia management To assess the efficacy and tolerance of sodium alginate compared to cisapride in patients suffering from reflux symptoms , without severe oesophagitis Nonerosive reflux disease ( NERD ) is the most common form of gastroesophageal reflux disease . Patients with NERD have a lower response rate to proton pump inhibitors ( PPIs ) than patients with erosive esophagitis when gauged from relief of heartburn . Sodium alginate decreases the acidity of refluxate and protects the esophageal mucosa . However , whether the addition of sodium alginate to PPI therapy can improve NERD symptoms remains unknown . Accordingly , the aim of this study was to evaluate the efficacy of adding sodium alginate to basal PPI therapy for NERD . Patients who had experienced heartburn on at least 2 days per week during the 1-month period before entering the study and had no endoscopic mucosal breaks ( grade M or N according to Hoshihara 's modification of the Los Angeles classification ) were r and omized to one of two treatments for 4 weeks : omeprazole ( 20 mg once daily ) plus sodium alginate ( 30 mL four times a day ) ( group A ) or omeprazole ( 20 mg once daily ) alone ( group B ) . Eighty-seven patients were enrolled , and 76 patients were r and omly assigned to group A ( n = 36 ) or group B ( n = 40 ) . Complete resolution of heartburn for at least 7 consecutive days by the end of treatment was significantly more common in group A ( 56.7 % ) than in group B ( 25.7 % ) . One patient from group A had mild drug-related diarrhea that was not clinical ly serious . In conclusion , omeprazole combined with sodium alginate was better than omeprazole alone in Japanese patients with NERD The aim of this study was to compare the efficacy of the sodium alginate preparation , Gaviscon Advance , with placebo in the relief of symptoms of reflux oesophagitis . This was a r and omised , double-blind , parallel-group , multicentre study conducted at 13 GP centres in the UK . Patients aged between 18 and 70 years , who had experienced symptoms of reflux oesophagitis within the previous 24 h , and on two other occasions within the previous week , were recruited into the study . Patients were evaluated at baseline , and then reassessed after two and four weeks of treatment with sodium alginate or placebo , for symptoms of reflux oesophagitis in the previous 24 h. Patients were required to fill out a diary card twice daily , from which frequency and severity of symptoms were assessed , and the percentage of symptom-free days and nights calculated . Of the 100 patients recruited into the study , 98 received medication ( safety population ; placebo , n = 50 ; sodium alginate , n = 48 ) and 94 were eligible for inclusion in the intention-to-treat ( ITT ) population ( placebo , n = 48 ; sodium alginate , n = 46 ) . For this population , sodium alginate was assessed as significantly superior by both investigators and patients at week two ( p < 0.001 and p = 0.004 , respectively ) and at week four ( p = 0.001 and p < 0.001 , respectively ) . Significantly more patients in the safety population on placebo withdrew from the study ( 40 % ) compared with sodium alginate ( 21 % ; p = 0.04 ) , due primarily to lack of effect and adverse events . The sodium alginate preparation demonstrated a superior efficacy compared with placebo , which was achieved in a more acceptable volume of medication than a previous st and ard preparation , Liquid Gaviscon . The reduced dosage volume of the ' new ' preparation ( Gaviscon Advance ) may be expected to improve patient compliance , and thereby increase treatment efficacy BACKGROUND & AIMS Alginate rafts ( polysaccharide polymers that precipitate into a low-density viscous gel when they contact gastric acid ) have been reported to form at the acid pocket , an unbuffered pool of acid that floats on top of ingested food and causes postpr and ial acid reflux . We studied the location of an alginate formulation in relation to the acid pocket and the corresponding effects on reflux parameters and acid pocket positioning in patients with gastroesophageal reflux disease ( GERD ) . METHODS We r and omly assigned patients with symptomatic GERD and large hiatal hernias to groups who were given either (111)In-labeled alginate-antacid ( n = 8 , Gaviscon Double Action Liquid ) or antacid ( n = 8 , Antagel ) after a st and ard meal . The relative positions of labeled alginate and acid pocket were analyzed for 2 hours by using scintigraphy ; reflux episodes were detected by using high-resolution manometry and pH-impedance monitoring . RESULTS The alginate-antacid label localized to the acid pocket . The number of acid reflux episodes was significantly reduced in patients receiving alginate-antacid ( 3.5 ; range , 0 - 6.5 ; P = .03 ) compared with those receiving antacid ( 15 ; range , 5 - 20 ) , whereas time to acid reflux was significantly increased in patients receiving alginate-antacid ( 63 minutes ; range , 23 - 92 ) vs those receiving antacid ( 14 minutes ; range , 9 - 23 ; P = .01 ) . The acid pocket was located below the diaphragm in 71 % of patients given alginate-antacid vs 21 % of those given antacid ( P = .08 ) . There was an inverse correlation between a subdiaphragm position of the acid pocket and acid reflux ( r = -0.76 , P < .001 ) . CONCLUSIONS In a study of 16 patients with GERD , we observed that the alginate-antacid raft localizes to the postpr and ial acid pocket and displaces it below the diaphragm to reduce postpr and ial acid reflux . These findings indicate the importance of the acid pocket in GERD pathogenesis and establish alginate-antacid as an appropriate therapy for postpr and ial acid reflux Forty-four patients with symptoms of gastro-oesophageal reflux were r and omly assigned in a crossover trial to treatment for 15-day periods with Liquid Gaviscon ( a reflux suppressant ) or an antacid gel containing magnesium and aluminium hydroxide . Good relief of symptoms was reported by 84 % of patients during therapy with Liquid Gaviscon compared to only 23 % during antacid therapy . Relief of symptoms was obtained within 15 minutes by 68 % of patients during therapy with Liquid Gaviscon compared to Output:	Alginates are more effective than placebo or antacids for treating GERD symptoms
MS21953	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Summary AIM : The aim of our study was to evaluate the accuracy of preoperative TNM staging with endoscopic ultrasound ( EUS ) in gastric cancer patients in comparison with the pathohistological stage of the resected specimen , and to determine the possible implication s of EUS for individualized treatment of gastric cancer patients at our institution . PATIENTS AND METHODS : The study included 82 patients operated for resectable gastric cancer between January 1st 2001 and July 1st 2003 at the Maribor Teaching Hospital Department of Abdominal and General Surgery . The EUS stage was assessed preoperatively at the Endoscopical Unit , and the pathohistological stage in the resected specimen was determined postoperatively at the Department of Pathologic Morphology according to recommended st and ards . RESULTS : Comparison of EUS and pathohistological assessment s revealed accuracy of EUS staging for locoregional tumor infiltration ( category T ) in 68 % of patients . The accuracy of EUS staging was 68 % for T1 , 69 % for T2 , 69 % for T3 and 60 % for T4 . Lymph nodes ( category N ) were correctly staged with EUS in 57 % of cases . The EUS stage was correct for lymph nodes with no metastases ( N− ) in 40 % of cases , and for lymph nodes with metastases ( N+ ) in 90 % . There was no significant difference in accuracy of EUS staging with regard to tumor site ( P = 0.768 ) or tumor size ( P = 0.766 ) . CONCLUSIONS : According to our results the accuracy of EUS staging matched pathohistological staging with regard to tumor infiltration and lymph node stage in 68 % and 57 % of cases respectively . Underestimation of the final T2 and T3 stages as T1 stage by EUS presents a problem regarding the consistency of EUS examination at our institution , particularly with respect to individual treatment for early gastric cancer . The present uncertainty in EUS stage reliability makes it necessary to have a strategy of radical resection with D2 lymphadenectomy in patients within EUS stages T1–T3 , with additional CT examinations in more advanced EUS stages in order to visualize the circumstances of tumor growth . Nevertheless , EUS provides an opportunity for the surgeon to gain more insight into the loco-regional circumstances of the gastric tumor process . For development of individual modes of treatment based on EUS staging , a more reliable assessment of EUS stage is m and atory BACKGROUND / AIMS Endoscopic ultrasonography is expected to be useful for invasion depth staging of early gastric cancer . A prospect i ve blind study of the staging characteristics of endoscopy and endoscopic ultrasonography for early gastric cancer was performed . METHODS Findings of endoscopy and endoscopic ultrasonography using a 20 MHz thin ultrasound probe were independently review ed and the results of 52 early gastric cancer lesions analysed . RESULTS The overall accuracy rates in invasion depth staging of early gastric cancer were 63 % for endoscopy and 71 % for endoscopic ultrasonography . No statistically significant differences were observed in overall accuracy . Endoscopic ultrasonography tended to overstage , and lesions that were classified as mucosal cancer by endoscopic ultrasonography were very likely ( 95 % ) to be limited to the mucosa on histological examination . All 16 lesions staged as mucosal cancer independently but coincidentally by both methods were histologically limited to the mucosa . CONCLUSIONS Endoscopic ultrasonography is expected to compensate for the understaging of lesions with submucosal invasion that are endoscopically staged as mucosal cancer BACKGROUND AND STUDY AIMS This study aim ed to compare the diagnostic accuracy of endoscopic ultrasonography ( EUS ) with that of conventional endoscopy for staging depth of invasion ( T staging ) in early gastric cancer . PATIENTS AND METHODS A total of 955 patients with suspected early gastric cancer were prospect ively registered . EUS staging was carried out prospect ively by a single endoscopist using either miniprobe or radial EUS depending on the endoscopic appearance of the tumor . Conventional endoscopy staging was performed retrospectively by consensus between two endoscopists who were blinded to the EUS staging . Conventional endoscopy staging was conducted on the basis of endoscopic features such as surface nodularity and fold convergence . Patients underwent either surgical ( n = 586 ) or endoscopic resection ( n = 369 ) with curative intent . The staging accuracy of each test was compared with the pathological staging of the resected specimen . RESULTS The presence of a T1 m tumor was histologically confirmed in 644 cases ( 67.4 % ) and that of a T1sm tumor in 311 cases ( 32.6 % ) . The overall accuracy of EUS staging was 67.4 % ( 644 / 955 ) and that of conventional endoscopy staging was 73.7 % ( 704 / 955 ) ( P < 0.001 ) . The accuracy of miniprobe EUS was significantly higher than that of radial EUS ( 79.5 % vs. 59.6 % , P < 0.001 ) , but did not differ significantly from that of conventional endoscopy ( 79.0 % ) . CONCLUSIONS EUS does not substantially impact on pretreatment T staging of patients with early gastric cancer compared with conventional endoscopy . Therefore , EUS may not be necessary routinely , and conventional endoscopy may be sufficient for determining the optimal therapeutic strategy , especially in relation to endoscopic resection for early gastric cancer Background Endoscopic ultrasonography ( EUS ) is an integrated part of the pretherapeutic evaluation program for patients with upper gastrointestinal ( GI ) tract cancer . Whether the clinical impact of EUS differs between surgeons from different countries is unknown . The same applies to the potential clinical influence of EUS misinterpretations . The aim of this study was to evaluate the interobserver agreement on predefined treatment strategies between surgeons from four different countries , with and without EUS , and to evaluate the clinical consequences of EUS misinterpretations . Methods One hundred patients with upper GI tract cancer were r and omly selected from all upper GI tract cancer patients treated at Odense University Hospital between 1997 and 2000 . Based on patient records and EUS data base results , a case story was created with and without the EUS result for each patient . Four surgeons were asked to select the relevant treatment strategy in each case , at first without knowledge of the EUS and thereafter with the EUS result available . Interobserver agreement and impact of EUS misinterpretations were evaluated using the actual final treatment of each patient as reference . Results Three of four or all four surgeons agreed on the same treatment strategy for nearly 60 % of the patients with and without the EUS results . Treatment decisions were changed in 34 % based on the EUS results , and the majority of these changes were toward nonsurgical and palliative treatments ( 85 % ) . Interobserver agreement was relatively low , but overall EUS increased kappa values from 0.16 ( “ poor ” ) to 0.33 ( “ fair ” ) , thus indicating increased overall agreement after the EUS results were available . EUS conclusion regarding stage or resectability was wrong in 17 % of the cases , but only one serious event would have been the clinical result of EUS misinterpretations . Conclusion Despite being used in different ways by different surgeons , EUS did change patient management in one third of the cases . The impact of EUS misinterpretations seemed very low , and this study confirmed one of the strongest clinical possibilities of EUS , i.e. , the ability to detect nonresectable cases . EUS is an important imaging modality for oncosurgeons from different countries Background Early gastric cancer ( EGC ) with undifferentiated histology has not been generally accepted as an indication for endoscopic treatment . This study was design ed to evaluate the outcomes and clinicopathological factors associated with the complete resection of undifferentiated EGC using endoscopic submucosal dissection ( ESD ) . Methods A retrospective analysis of prospect ively collected data was performed on consecutive patients who underwent ESD . Among the 456 EGCs treated using ESD at the Seoul National University Hospital , Seoul , Korea , between April 2005 and June 2008 , 60 lesions ( 13.2 % ) were diagnosed as undifferentiated gastric cancer ( poorly differentiated adenocarcinoma or signet ring cell carcinoma ) . Results En bloc resection was performed in all lesions without significant complications . The size discrepancy between the pretreatment endoscopy and the resected specimen was significantly higher in undifferentiated EGCs than differentiated EGCs ( p = 0.002 ) . The complete resection rate was significantly lower for undifferentiated EGC ( 55 % ) cases than differentiated EGC cases ( 84.1 % ; p < 0.001 ) . Independent risk factors for incomplete resection of undifferentiated EGC included tumor size > 20 mm , submucosal invasion , and presence of ulceration . During a mean observation time of 16 months , no recurrence developed in any of the patients with undifferentiated EGCs thought to be completely resected by ESD . Conclusions ESD might be considered an alternative treatment modality in carefully selected cases of undifferentiated EGC Conventional imaging studies are often not sensitive enough to allow accurate preoperative staging of intra-abdominal tumour spread . Laparoscopy and laparoscopic ultrasound appear to be suitable to improve staging of gastrointestinal tumors . Within a 10-month period 40 patients with upper GI tract cancer underwent laparoscopy for intra-abdominal staging . Additionally laparoscopic ultrasound was performed on 20 of these patients using a flexible echo-endoscope equipped with a curved array transducer ( 5/7.5 MHz ) . By laparoscopy additional information compared to conventional staging was obtained in 16 patients ( 40 % ) . Laparoscopy revealed peritoneal carcinomatosis and liver metastases in seven and four patients , respectively . M1-lymph nodes were detected in four patients . Laparoscopic ultrasound was able to image otherwise inaccessible regions of the abdominal cavity and induced a change of staging in seven of 20 patients in whom laparoscopy was uneventful . Ultrasound also proved to be valuable for localization of M1-lymph nodes . In summary , combination of laparoscopy and laparoscopic ultrasound improved staging in 23 of 40 patients ( 57 % ) . Consequently surgery was ab and oned in 16 patients due to incurable or non-resectable disease , while down-staging occurred in seven patients , who subsequently underwent resection . Laparoscopy is capable of improving staging of intra-abdominal malignancy by detection and subsequent biopsy of small lesions . Laparoscopic ultrasound can replace the lack of tactile sensitivity in laparoscopy , thus enabling the detection of non-superficial lesions Background : Local and multimodal therapeutic strategies for tumours of the oesophagus and gastric cardia , require precise preoperative staging . Endosonography is considered the most accurate staging method , while computed tomography ( CT ) has limitations especially in the evaluation of local infiltration . Macroscopic endoscopic evaluation was reported to be accurate in selected series , but no study has yet compared all three staging modalities . Methods : One hundred and seventeen unselected patients with tumours of the oesophagus and gastric cardia were prospect ively staged first by the endoscopic macroscopic appearance and then by endosonography . All patients had preoperative CT scans , however , only the 36 patients receiving the scans at our institution were included in the study . The preoperative staging results were then compared to postoperative histology which was available as the gold st and ard in all included patients . Kappa statistics were used to exclude chance agreement of the clinical staging results with the pathohistological findings . Differences between the result ing ĸ values for the different staging modalities were analysed with a jack-knife test . Results : Endoscopic macroscopic staging and endosonography ( accuracy 67 and 69 % , weighted ĸ 0.78 and 0.84 ) were significantly more accurate than CT ( accuracy 33 % , weighted ĸ 0.44 ) for determination of the T category ( p = 0.006 and p = 0.001 ) . After exclusion of tumours of the cardia ( n = 33 ) , the accuracy of macroscopic and endosonographic staging ( accuracy 72 and 75 % , weighted ĸ 0.86 and 0.88 ) increased and remained more accurate than CT ( accuracy 50 % , weighted ĸ 0.62 ) . The main pitfall in our series in staging the T category was the overestimation of T2 tumours in the cardia as T3 or even as T4 tumours due to the inability to visualise the serosa . The accuracy of predicting lymph node metastasis was 68 % for macroscopic endoscopic , 79 % for endosonographic , and 67 % for CT staging . Only endosonographic staging was significantly different from chance agreement with histology ( weighted ĸ = 0.56 ) . Endosonographic staging was significantly more accurate than endoscopic macroscopic and CT staging ( p = 0.03 ) . Conclusions : Endosonography is the most accurate staging modality for overall preoperative staging of oesophageal and cardial tumours . Endoscopic macroscopic staging allows a reasonably accurate assessment of the T category BACKGROUND AND STUDY Output:	Overall , as demonstrated also by the Bayesian nomograms , which enable readers to calculate post-test probabilities for any target condition prevalence , the EUS accuracy can be considered clinical ly useful to guide physicians in the locoregional staging of people with gastric cancer . Moreover , we must emphasize that the analysis of positive and negative likelihood values revealed that EUS diagnostic performance can not be considered optimal either for disease confirmation or for exclusion , especially for the ability of EUS to distinguish T1a ( mucosal ) versus T1b ( submucosal ) cancers and positive versus negative lymph node status . By analyzing the data from the largest series ever considered , we found that the diagnostic accuracy of EUS might be considered clinical ly useful to guide physicians in the locoregional staging of people with gastric carcinoma . Moreover , physicians should be warned that EUS performance is lower in diagnosing superficial tumors ( T1a versus T1b ) and lymph node status ( positive versus negative ) .
MS21954	*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 Social cognition difficulties in schizophrenia are seen as a barrier to recovery . Intervention tackling problems in this domain have the potential to facilitate functioning and recovery . Social Cognition and Interaction Training ( SCIT ) is a manual-based psychological therapy design ed to improve social functioning in schizophrenia . AIMS The aim of this study is to evaluate the feasibility and acceptability of a modified version of SCIT for inpatient forensic wards . The potential benefits of the intervention were also assessed . METHOD This study is a r and omized single blind controlled design , with participants r and omized to receive SCIT ( N = 21 ) or treatment as usual ( TAU ; N = 15 ) . SCIT consisted of 8-week therapy sessions twice per week . Participants were assessed at week 0 and one week after the intervention on measures of social cognition . Feasibility was assessed through group attendance and attrition . Participant acceptability and outcome was evaluated through post-group satisfaction and achievement of social goals . RESULTS The intervention was well received by all participants and the majority reported their confidence improved . The SCIT group showed a significant improvement in facial affect recognition compared to TAU . Almost all participants agreed they had achieved their social goal as a result of the intervention . CONCLUSIONS It is feasible to deliver SCIT in a forensic ward setting ; however , some adaptation to the protocol may need to be considered in order to accommo date for the reduced social contact within forensic wards . Practice of social cognition skills in real life may be necessary to achieve benefits to theory of mind and attributional style Background There is a broad literature suggesting that cognitive difficulties are associated with violence across a variety of groups . Although neurocognitive and social cognitive deficits are core features of schizophrenia , evidence of a relationship between cognitive impairments and violence within this patient population has been mixed . Methods We prospect ively examined whether neurocognition and social cognition predicted inpatient violence amongst patients with schizophrenia and schizoaffective disorder ( n = 89 ; 10 violent ) over a 12 month period . Neurocognition and social cognition were assessed using the MATRICS Consensus Cognitive Battery ( MCCB ) . Results Using multivariate analysis neurocognition and social cognition variables could account for 34 % of the variance in violent incidents after controlling for age and gender . Scores on a social cognitive reasoning task ( MSCEIT ) were significantly lower for the violent compared to nonviolent group and produced the largest effect size . Mediation analysis showed that the relationship between neurocognition and violence was completely mediated by each of the following variables independently : social cognition ( MSCEIT ) , symptoms ( PANSS Total Score ) , social functioning ( SOFAS ) and violence proneness ( HCR-20 Total Score ) . There was no evidence of a serial pathway between neurocognition and multiple mediators and violence , and only social cognition and violence proneness operated in parallel as significant mediators accounting for 46 % of the variance in violent incidents . There was also no evidence that neurocogniton mediated the relationship between any of these variables and violence . Conclusions Of all the predictors examined , neurocognition was the only variable whose effects on violence consistently showed evidence of mediation . Neurocognition operates as a distal risk factor mediated through more proximal factors . Social cognition in contrast has a direct effect on violence independent of neurocognition , violence proneness and symptom severity . The neurocognitive impairment experienced by patients with schizophrenia spectrum disorders may create the foundation for the emergence of a range of risk factors for violence including deficits in social reasoning , symptoms , social functioning , and HCR-20 risk items , which in turn are causally related to violence Individuals with antisocial personality disorder ( ASPD ) are impulsive and show impairment in reinforcement processing . There is increasing evidence for a neurobiological basis of psychopathy , which shares some of the characteristics of ASPD , but research on the neuronal correlates of neuropsychological processes in ASPD remains limited . Furthermore , no research has examined the effects of serotonergic manipulation on brain activations in antisocial groups . In this study , 25 male participants with ASPD ( mean age 42.1 ) and 32 male control participants ( mean age 30.5 ; 25 participants providing usable scans ) were r and omly allocated to receive the 5-HT(2C)-agonist mCPP or placebo . Participants were scanned using functional magnetic resonance imaging ( fMRI ) during a behavioural inhibition ( Go/NoGo ) and a reward task . In comparison to healthy controls the ASPD group showed reduced task related activations in the dorsolateral prefrontal cortex ( DLPFC ) but increased signal in the pre/subgenual anterior cingulate cortex ( ACC ) in the Go/No-Go task and increased activation in OFC in the reward task . mCPP modulated brain responses in both tasks in the whole group . Interactions between group and drug occured in bilateral OFC , cau date and ventral pallidum during the reward task but no significant interactions were found in the Go/No-Go task . This suggests that ASPD involves altered serotonin modulation of reward , but not motor inhibition pathways . These findings suggest that ASPD involves altered DLPFC , ACC and OFC function . Altered serotonergic modulation of reward pathways seen in the ASPD group raises the possibility that targeting serotonin systems may be therapeutic Objective : There is a need to find effective treatments for individuals with antisocial and borderline personality disorder who are known to be difficult to engage and treat . Many of these individuals share considerable overlap with symptoms of ADHD , hence this study aim ed to evaluate the Reasoning and Rehabilitation ADHD program ( R&R2 ADHD ) among patients with severe personality disorder . Method : A total of 31 males detained in a “ dangerous and severe personality disorder ” unit completed question naires at baseline and post treatment to assess social problem solving , violent attitudes , anger , ADHD symptoms , emotional control , and social functioning . A total of 16 patients participated in the group condition , and their scores were compared with 15 waiting-list controls who received treatment as usual . Results : In all , 76 % of group participants completed the program . In contrast to controls , they showed significant improvements in scores with mainly medium effect sizes . Conclusion : R&R2 ADHD was effective in a small sample of severely personality-disordered offenders The role of mentalizing abilities ( or theory of mind ) and empathic abilities in violent behavior were studied in 24 hospitalized males with paranoid schizophrenia ( ICD-10 ) . Patients were divided into violent and nonviolent groups based on their history of committing violent acts against others . To examine these abilities , patients heard a series of 12 short scenarios depicting social situations followed by questions that require making mental state or empathic inferencing . Our results show that violent patients have more difficulties than nonviolent patients in tasks involving empathic inferencing , and better abilities in inferring cognitive-mental states in others . In addition , violence seems to be associated with a history of alcohol and drug abuse , young age , and the hostility component of the Brief Psychiatric Rating Scale . Logistic regression analyses suggest that violence is associated with the combination of hostility towards others , good mentalizing abilities and poor empathy . These results are discussed in light of recent theories on violent behavior in psychiatric population Cognitive remediation has proven efficacy for improving neurocognition in people with schizophrenia . The current study evaluated the benefits of cognitive remediation on neurocognition , functioning , psychotic symptoms , and aggression in a sample of forensic and mental health patients . Care recipients with schizophrenia or schizoaffective disorder ( N = 78 ) receiving services in the forensic and mental health units of a state hospital were r and omized to participate in cognitive remediation versus computer games control activities . Participants ' neurocognition , functional capacity , experiential recovery , psychotic symptoms , and aggression incidents were assessed at baseline and posttreatment . Cognitive remediation was associated with improvements in several neurocognitive domains and circumscribed domains of functional capacity . People assigned to cognitive remediation experiences greater reductions in negative symptoms , agitation/excitement , and verbal and physical aggression . In addition to improving neurocognition in long-term hospitalized forensic and mental health patients , cognitive remediation may enhance efforts at reducing negative symptoms , emotion dysregulation , and aggression incidents . Forensic setting s may represent a new frontier for the clinical dissemination of cognitive remediation Cognitive Behavioral Social Skills Training ( CBSST ) is a 24-session weekly group therapy intervention to improve functioning in people with schizophrenia . In our prior r and omized clinical trial comparing treatment as usual ( TAU ) with TAU plus group CBSST ( Granholm , E. , McQuaid , J.R. , McClure , F.S. , Ausl and er , L. , Perivoliotis , D. , Pedrelli , P. , Patterson , T. , Jeste , D.V. , 2005 . A r and omized controlled trial of cognitive behavioral social skills training for middle-aged and older out patients with chronic schizophrenia . Am . J. Psychiatry 162 , 520 - 529 . ) , participants with schizophrenia in CBSST showed significantly better functional outcome than participants in TAU . The present study was a secondary analysis of neuropsychological predictors of functional outcome in our prior CBSST trial . We examined ( 1 ) whether neuropsychological impairment at baseline moderated functional outcome in CBSST relative to TAU , and ( 2 ) whether improvement in neuropsychological abilities mediated improvement in functional outcome in CBSST . Attention , verbal learning/memory , speed of processing , and executive functions were assessed at baseline , end of treatment , and 12-month follow-up . Greater severity of neuropsychological impairment at baseline predicted poorer functional outcome for both treatment groups ( nonspecific predictor ) , but the interaction between severity of neuropsychological impairment and treatment group was not significant ( no moderation ) . Effect sizes for the difference between treatment groups on functional outcome measures at 12-month follow-up were similar for participants with relatively mild ( d=.44-.64 ) and severe ( d=.29-.60 ) neuropsychological impairment . Results also did not support the hypothesis that improvement in neuropsychological abilities mediated improvement in functioning in CBSST . Adding CBSST to st and ard pharmacologic care , therefore , improved functioning relative to st and ard care alone , even for participants with severe neuropsychological impairment , and this improvement in functioning was not related to improvement in neuropsychological abilities in CBSST Output:	Results : Meta-analyses indicated lower IQ , memory and executive function in both violent schizophrenia and antisocial personality disorder groups compared to healthy controls . The degree of deficit was consistently larger in violent schizophrenia . Both antisocial personality disorder and violent schizophrenia groups had difficulties in aspects of facial affect recognition , although theory of mind results were less conclusive . Psychopathic traits related positively to experiential emotion deficits across the two disorders . Conclusion : There are qualitatively similar , but quantitatively different , neuropsychological and emotion processing deficits in violent individuals with schizophrenia and antisocial personality disorder which could be developed into transdiagnostic treatment targets for violent behaviour .
MS21955	*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 therapeutic equivalence and safety of once daily ( OD ) versus three times daily ( TID ) dosing of a total daily dose of 3 g Salofalk ( mesalazine ) granules in patients with active ulcerative colitis . Design : A r and omised , double-blind , double-dummy , parallel group , multicentre , international , phase III non-inferiority study . Setting : 54 centres in 13 countries . Patients : 380 patients with confirmed diagnosis of established or first attack of ulcerative colitis ( clinical activity index (CAI)>4 and endoscopic index ⩾4 at baseline ) were r and omised and treated . Interventions : 8-week treatment with either 3 g OD or 1 g TID mesalazine granules . Main outcome measures : Clinical remission ( CAI⩽4 ) at study end . Results : 380 patients were evaluable for efficacy and safety by intention-to-treat ( ITT ) ; 345 for per protocol ( PP ) analysis . In the ITT population , 79.1 % in the OD group ( n = 191 ) and 75.7 % in the TID group ( n = 189 ) achieved clinical remission ( p<0.0001 for non-inferiority ) . Significantly more patients with proctosigmoiditis achieved clinical remission in the OD group ( 86 % ; n = 97 ) versus the TID group ( 73 % ; n = 100 ; p = 0.0298 ) . About 70 % of patients in both treatment groups achieved endoscopic remission , and 35 % in the OD group and 41 % in the TID group achieved histological remission . About 80 % of all patients preferred OD dosing . Similar numbers of adverse events occurred in 55 patients ( 28.8 % ) in the OD group and in 61 patients ( 32.3 % ) in the TID group , indicating that the two dosing regimens were equally safe and well tolerated . Conclusions : OD 3 g mesalazine granules are as effective and safe as a TID 1 g schedule . With respect to the best possible adherence of patients to the treatment , OD dosing of mesalazine should be the preferred application mode in active ulcerative colitis . Clinical Trials.gov Identifier : Background and Aims Multiple studies have demonstrated the efficacy of aminosalicylates in maintaining remission in ulcerative colitis ( UC ) . A newer formulation of mesalamine can be administered once daily . We aim ed to examine the efficacy and tolerability of pH-dependent mesalamine for long-term maintenance , and compare the rates of medication consumption between groups over a prolonged period . Methods Subjects whose UC had been quiescent for at least 4 months , and who had been receiving mesalamine for maintenance only , were r and omized to once daily or conventional dosing for 12 months . Disease activity and medication consumption was assessed every 3 months . The primary endpoint was the percentage of those with quiescent disease at 12 months . Results We enrolled 20 patients , 12 to once daily and 8 to conventional dosing . Six of the 12 patients ( 50 % ) in the once daily group compared with 5 of the 8 patients ( 62.5 % ) in the conventional group experienced a flare ( p = 0.31 ) . Only 5 of the 12 ( 42 % ) patients in the once daily group were adherent compared with 3 of 8 patients ( 37.5 % ) in the conventional dosing group ( p = NS ) . Median amount consumed in the once daily group was 63 % ( range 0%–100 % ) and in the conventional group 55 % ( range 0%–100 % ) , ( p > 0.5 ) . None of the adherent subjects in the once daily group experienced a flare , while 6 out of 7 ( 86 % ) who were non-adherent experienced a flare ( p < 0.01 ) . In the conventional dosing group , 1 in 3 adherent patients ( 33 % ) experienced a flare compared with 4 out of 5 ( 80 % ) in the non-adherent group ( p < 0.01 ) . Conclusion Adherence , rather than medication regimen , appeared to be important in disease outcome at 12 months Background : Mesalazine ( Asacol ) is still widely prescribed in divided doses for ulcerative colitis ( UC ) , despite evidence that adherence is improved by once‐daily ( OD ) prescribing . We aim ed to investigate whether OD Asacol was as effective as three times ( TDS ) daily dosing , and to evaluate the role of treatment adherence . Methods : An investigator‐blind r and omized trial was undertaken comparing OD Asacol ( three 800 mg tablets ) versus one 800 mg TDS in maintenance of remission of UC over 1 year . The primary endpoint was relapse rate , and noninferiority would be concluded if the lower limit of the two‐sided 95 % confidence interval ( CI ) of the difference in proportions relapsing ( TDS‐OD ) exceeded −10 % . Adherence was measured by tablet counts and self‐reported adherence . A subgroup of patients used a bottle cap that recorded all bottle opening events . Results : In all , 213 patients were r and omized . In the intention‐to‐treat ( ITT ) population , relapse rates were 31 % ( 95 % CI 22%–40 % ) in the OD and 45 % ( 95 % CI 35%–54 % ) in the TDS group . Primary analysis confirmed the noninferiority of OD dosing . Two of the study population s , ITT and per‐ protocol ( PP ) , showed potential superiority of OD dosing . All measures of adherence showed that it was significantly better in the OD group . Multivariate analysis , however , showed OD dosing was associated with lower relapse risk independently of adherence . Conclusions : OD dosing with Asacol 2.4 g is as safe and effective as TDS dosing , and secondary analysis confirmed significantly reduced relapse rates . The benefit , however , was clinical ly borderline and may relate in part to ease of adherence . ( Inflamm Bowel Dis 2012 BACKGROUND & AIMS SPD476 ( MMX mesalamine ) , a novel , once-daily mesalamine formulation , uses MMX Multi Matrix System ( MMX ) technology to delay and extend delivery of active drug throughout the colon . We performed a r and omized , double-blind , parallel-group , placebo-controlled , multicenter phase III study in patients with mild to moderately active ulcerative colitis . METHODS Two hundred eighty patients with mild to moderately active ulcerative colitis received MMX mesalamine 2.4 g/day given twice daily ( n = 93 ) , 4.8 g/day given once daily ( n = 94 ) , or placebo ( n = 93 ) for 8 weeks . The primary end point was the percentage of patients in clinical and endoscopic remission ( modified ulcerative colitis disease activity index score of < or = 1 , with a score of 0 for rectal bleeding and stool frequency , and at least a 1-point reduction in sigmoidoscopy score ) at week 8 . Patients with mucosal friability were not considered to have achieved this end point . RESULTS Clinical and endoscopic remission at week 8 was achieved by 34.1 % and 29.2 % of patients receiving MMX mesalamine 2.4 g/day given twice daily and MMX mesalamine 4.8 g/day given once daily , respectively , versus 12.9 % receiving placebo ( P < .01 ) . MMX mesalamine was generally well-tolerated . CONCLUSIONS MMX mesalamine given once or twice daily is well-tolerated and , compared with placebo , demonstrated efficacy for the induction of clinical and endoscopic remission in mild to moderately active ulcerative colitis BACKGROUND & AIMS This study was conducted to assess , in a small sample , the short-term outcomes of once-daily mesalamine versus conventional dosing in maintaining quiescent ulcerative colitis ( UC ) and to assess adherence rates with both regimens . METHODS Consecutive patients were r and omly assigned to either a once-daily regimen , or they continued current conventional regimen ( twice daily or 3 times daily ) . Patients were assessed at 3 months and 6 months . At each point , a clinical symptom disease score was obtained using patient question naires , and medication rates via pharmacy data . Adherence was defined as consumption of > 80 % of prescribed medication . Information was collected by an investigator blinded to treatment regimen . RESULTS Twenty-two patients were enrolled in the study , 12 in the once-daily group ( QD ) and 10 in the conventional group ( CD ) . At 3 months , no patients had experienced a relapse . All of the patients in the QD group and 70 % of patients in the CD group were adherent ( P = 0.04 ) . The average amount of medication consumed in the QD group was significantly higher than in the CD group ( 90 % vs. 75 % , P = 0.02 ) . At 6 months , 2 patients ( 1 patient from each group ) experienced a clinical relapse ( P = 0.76 ) . Seventy-five percent vs. 70 % of patients were adherent ( P = 0.8 ) ; the amount of medication taken approached significance ( 90 % vs. 76 % , P = 0.07 ) . All patients in the QD group reported being either " very satisfied " or " satisfied " with their regimen . CONCLUSIONS In this r and omized pilot trial , patients taking once-daily mesalamine had outcomes similar to those for patients on conventional regimens . A larger trial is warranted to assess whether true differences between regimens exist BACKGROUND & AIMS The practice of dosing mesalamines in divided doses for the treatment of ulcerative colitis ( UC ) began with sulfasalazine and was driven by sulfapyridine toxicity . This convention and the assumption that dosing multiple times a day is necessary to treat UC had not been challenged until recently . This study was conducted to determine the efficacy and safety of once-daily dosing of delayed-release mesalamine ( Asacol 400-mg tablets ) compared with twice-daily dosing for maintaining remission in UC patients . METHODS A multicenter , r and omized , investigator-blinded , 12-month , active-control trial was conducted to assess the noninferiority of delayed-release mesalamine 1.6 - 2.4 g/day administered once daily compared with twice daily in patients with mild-to-moderate UC currently in clinical remission . The primary end point was maintenance of clinical remission at month 6 . RESULTS A total of 1023 patients were r and omized and dosed . The primary objective of noninferiority was met . At month 6 , 90.5 % of patients receiving once-daily dosing had maintained clinical remission , compared with 91.8 % of patients receiving twice-daily dosing ( 95 % confidence interval for twice daily - once daily , -2.3 to 4.9 ) . At month 12 , 85.4 % of patients receiving once-daily dosing had maintained clinical remission , compared with 85.4 % of patients receiving twice-daily dosing ( 95 % confidence interval for twice daily - once daily , -4.6 to 4.7 ) . Both regimens had low rates of withdrawals as a result of adverse events and serious adverse events . CONCLUSIONS Once-daily dosing of delayed-release mesalamine at doses of 1.6 - 2.4 g/day was shown to be as effective as twice-daily dosing for maintenance of clinical remission in patients with UC Background : Ulcerative colitis ( UC ) , a chronic , relapsing , and remitting inflammatory bowel disease , requires long-term treatment to maintain remission . In this study , the long-term safety and tolerability of mesalamine granules ( MG ) therapy was evaluated in the maintenance of UC remission . Previous prospect i ve studies evaluating different oral mesalamine formulations have not exceeded a duration of 14 months . Methods : A phase 3 , multicenter , 24-month , open-label extension study evaluating MG 1.5 g once daily in patients who achieved previous remission from mild to moderate UC was performed . Eligible patients had successfully participated in 1 of 2 previous 6-month double-blind , placebo-controlled trials or were new patients in remission . Safety assessment s included monitoring of adverse events ( AEs ) and clinical laboratory tests . Risk of UC recurrence was assessed by the occurrence of UC-related AEs . Results : Of the 393 patients enrolled ( 280 from the double-blind studies ; 113 new patients ) , 388 were included in the safety population . The most common AEs included nasopharyngitis ( 13.9 % ) , headache ( 11.6 % ) , and diarrhea ( 10.8 % ) , and the incidence of these events was generally lower in the MG group versus historical placebo group from the double-blind studies . Pancreatic , renal , and hepatic AEs occurred in 23 patients ( 5.9 % ) . The risk of UC-related AEs was low and was maintained for 24 months during the open-label study . Conclusions : Once-daily MG has a favorable safety profile for the maintenance of remission for up to 2 years in patients with UC BACKGROUND & AIMS SPD476 ( LIALDA in the US ; MEZAVANT in the EU ; otherwise known as MMX mesalamine ; Shire Pharmaceuticals Inc. , Wayne , PA , under license from Giuliani SpA , Milan , Italy ) is a novel , once-daily , high- Output:	No significant differences were noted in rates of medication adherence or adverse events between OD and MD dosing . With regard to mesalamine suppository , no significant differences were noted for comparisons between dosing regimens and adverse events for induction of remission . OD dose of mesalamine is as effective and safe as MD doses for the induction and maintenance treatment of mild to moderate UC . OD mesalamine given as a suppository can attain the same effect and safety as MD mesalamine in inducing remission of mild to moderate ulcerative colitis
MS21956	*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 We studied the prevalence of chronic pain and long term sensory changes after cosmetic augmentation mammoplasty and the effects of a single i.v . preoperative dose of methylprednisolone 125 mg ( n = 74 ) , parecoxib 40 mg ( n = 71 ) , or placebo ( n = 74 ) . A question naire was mailed 6 weeks and 1 year after surgery . Response rate after 1 year was 80 % . At 1 year non‐evoked pain was present in 13 % , and evoked pain was present in 20 % with no statistically significant differences between the groups . Methylprednisolone was associated with reduced odds for hyperesthesia at 1 year ( OR 0.3 , 95 % CI 0.1–0.6 ) , and significantly reduced the prevalence of hyperesthesia ( 30 % ) compared with placebo ( 56 % , P < 0.01 ) and parecoxib ( 51 % , P < 0.04 ) . Factors associated with increased odds for pain at 1 year were intensity of pain during the first 6 days after surgery ( OR 1.3 , 95 % CI 1.1–1.6 ) , pain at 6 weeks ( OR 18.4 , 95 % CI 6.9–49.3 ) , hyperesthesia at 6 weeks ( OR 2.3 , 95 % CI 1.1–5.1 ) and present hyperesthesia ( OR 3.1 , 95 % CI 1.4–6.7 ) . We conclude that persistent pain and sensory changes are common after augmentation mammoplasty , and that patients having pain at 6 weeks most likely will have pain also at 1 year . Acute postoperative pain , hyperesthesia at 6 weeks , and the presence of hyperesthesia increased the odds for pain at 1 year . Preoperative methylprednisolone result ed in significantly less hyperesthesia compared with both parecoxib and placebo , but did not significantly reduce the prevalence of persistent spontaneous or evoked pain Background : Sympathetic blockade with local anesthetics is used frequently in the management of complex regional pain syndrome type 1(CRPS-1 ) , with variable degrees of success in pain relief . The current study investigated which signs or symptoms of CRPS-1 could be predictive of outcome . The incidence of side effects and complications of sympathetic blockade also were determined prospect ively . Methods : A prospect i ve observational study was done of 49 patients with CRPS-1 in one extremity only and for less than 1-yr duration who had severe pain and persistent functional impairment with no response to st and ard treatment with medication and physical therapy . Results : Fifteen ( 31 % ) patients had good or moderate response . The response rate was not different in patient groups with cold or warm type CRPS-1 or in those with more or less than 1.5 ° C differential increase in skin temperature after sympathetic blockade . Allodynia and hypoesthesia were negative predictors for treatment success in CRPS-1 . There were no symptoms or signs of CRPS-1 that positively predicted treatment success . A majority of patients ( 84 % ) experienced transient side effects such as headache , dysphagia , increased pain , backache , nausea , blurred vision , groin pain , hoarseness , and hematoma at the puncture site . No major complications were reported . Conclusions : The presence of allodynia and hypoesthesia are negative predictors for treatment success . The selection of sympathetic blockade as treatment for CRPS-1 should be balanced carefully between potential success and side effect ratio . The procedure is as likely to cause a transient increase in pain as a decrease in pain . Patients should be informed accordingly BACKGROUND Spinal cord stimulation ( SCS ) has proven to be an effective however an invasive and relatively expensive treatment of chronic Complex Regional Pain Syndrome type 1(CRPS-1 ) . Furthermore , in one third of CRPS-1 patients , SCS treatment fails to give significant pain relief and 32 - 38 % of treated patients experience complications . The aim of the current study was to develop effective prognostic factors for prediction of successful outcome of SCS . METHODS AND RESULTS The study population consisted of 36 chronic CRPS patients enrolled in a r and omized controlled trial of SCS efficacy . We analyzed various prognostic factors in the group of patients treated with SCS and compared baseline values of possible predictors of outcome in the successfully treated and the not successfully treated group . Success was defined as Patient Global Perceived Impression of Change score of at least " much improved " and pain reduction of at least 2.5 on a visual-analogue scale ( VAS score 0 - 10 ) . Univariate analyses showed that patient age , duration of the disease , localization of the disease , intensity of the pain , and the presence of mechanical hypoesthesia did not predict SCS success . The mean and maximum value of brush-evoked allodynia proved to be statistically significant predictors of outcome . Using Receiver-Operating Characteristic ( ROC ) curve analyses of maximum allodynia values , the diagnostic sensitivity for successful SCS was 0.75 and the specificity 0.81 . CONCLUSION Brush-evoked allodynia may be a significant negative prognostic factor of SCS treatment outcome after 1 year in chronic CRPS-1 Background Herpes zoster ( HZ ) is a common disease , characterized by rash-associated localized pain . Its main complication , post-herpetic neuralgia ( PHN ) , is difficult to treat and may last for months to years in the wake of rash resolution . Uncertainties remain as to the knowledge of predictors of HZ-related pain , including the role of antiviral therapy in preventing PHN in ordinary clinical practice . This prospect i ve cohort study was aim ed at investigating pain intensity at HZ presentation and its correlates , as well as the incidence of PHN and its predictors . Methods Patients diagnosed with HZ were consecutively enrolled by a network of Italian General Practitioners and Hospital Units in the health district of Pescara , Italy , over two years . Uncertain cases were referred for microbiological investigation . Data were collected through electronic case report form ( e-CRFs ) at enrolment and at 1 , 3 , 6 and 12 months after enrolment . Pain intensity was coded on a five-degree semi-quantitative scale at each time point . PHN was defined as pain of any intensity during follow-up and quantified using an area-under-the-curve ( AUC ) method . Results Four hundred and forty-one patients composed the final sample . Mean age was 58.1 years ( SD = 20.4 years ) ; 43.5 % of patients were males ; 7.9 % did not receive prescription of antivirals . Intense/very intense pain at presentation was reported by 25.2 % of patients and was significantly associated with female gender , older age , cigarette smoking , trauma and /or surgery at HZ site ( logistic regression ) . PHN was diagnosed in 51.2 % of patients at one month and in 30.0 % of patients at three months . PHN was significantly associated with pain intensity at presentation , age , smoking , trauma and missed antiviral prescription ( generalized estimating equations model ) . The same factors were also independent predictors of the overall pain burden as described by the AUC method ( linear regression ) . Conclusions Smoking , traumas and surgery at the HZ site emerged as new predictors of both HZ-related pain intensity and persistence , opening new perspectives in the prevention of HZ-related pain . An independent line of evidence was provided for the efficacy of antiviral therapy in preventing PHN and reducing total pain burden Summary Despite early diagnosis and treatment with antiviral agents , many herpes zoster patients report persistent pain and marked long‐term reduction in health‐related quality of life . Abstract Underst and ing the effect of herpes zoster and zoster‐related pain should inform care to improve health‐related quality of life in elderly patients . A 12‐month , longitudinal , prospect i ve , multicenter observational study conducted in primary care in France enrolled patients aged ⩾50 years with acute eruptive herpes zoster . Patient‐reported zoster‐related pain was assessed by vali date d question naires ( Douleur Neuropathique en 4 Questions [ DN4 ] , Zoster Brief Pain Inventory [ ZBPI ] , and Neuropathic Pain Symptom Inventory [ NPSI ] ) on days 0 and 15 , and at months 1 , 3 , 6 , 9 , and 12 . Health‐related quality of life was assessed by the 12‐item short‐form health survey ( SF‐12 ) and the Hospital Anxiety and Depression scale on day 0 and at months 3 , 6 , and 12 . Of 1358 patients included , 1032 completed follow‐up . Mean ± st and ard deviation age was 67.7 ± 10.7 ( range , 50–95 ) years ; 62.2 % were women . Most patients ( 94.1 % ) were prescribed antiviral drugs . The prevalence of zoster‐related pain on day 0 and at months 3 , 6 , 9 , and 12 was 79.6 % , 11.6 % , 8.5 % , 7.4 % , and 6.0 % , respectively . Patients with persistent pain had lower scores on the physical and mental component summaries of the SF‐12 and the ZBPI interference score than those without pain . By logistic regression analysis , main predictive factors on day 0 for postherpetic neuralgia at month 3 were age , male sex , ZBPI interference score , Physical Component Summary score of the SF‐12 , and neuropathic quality of pain ( DN4 score ⩾4 ) . Despite early diagnosis and treatment with antiviral agents , many patients with herpes zoster experience persistent pain and marked long‐term reduction in health‐related quality of life Background : Women scheduled to undergo hysterectomy for benign indications frequently have preoperative pelvic pain , but it is largely unknown why pain in some cases persists or even develops after surgery . This nationwide question naire and data base study describes pain and identifies risk factors for chronic postsurgical pain 1 yr after hysterectomy for benign indications . Methods : A pain question naire was mailed to 1,299 women 1 yr after hysterectomy . The response rate was 90.3 % , and the presence of persistent pain was correlated to indication for surgery , surgical procedure , type of anesthesia , and other perioperative data . Results : Pain was reported by 31.9 % 1 yr after hysterectomy ( chronic pain ) , and 13.7 % had pain more than 2 days a week . Pain was not present before surgery in 14.9 % of women with chronic postsurgical pain . Risk factors for chronic pain were preoperative pelvic pain ( odds ratio [ OR ] , 3.25 ; 95 % confidence interval [ CI ] , 2.40–4.41 ) , previous cesarean delivery ( OR , 1.54 ; CI , 1.06–2.26 ) , pain as the main indication for surgery ( OR , 2.98 ; CI , 1.54–5.77 ) , and pain problems elsewhere ( OR , 3.19 ; CI , 2.29–4.44 ) . Vaginal hysterectomy versus total abdominal hysterectomy was not significantly associated with a lower risk of chronic pain ( OR , 0.70 ; CI , 0.46–1.06 ) . Importantly , spinal versus general anesthesia was associated with less chronic pain ( OR , 0.42 ; CI , 0.21–0.85 ) . Conclusions : Thirty-two percent had chronic pain after hysterectomy , and risk factors were comparable to those seen in other operations . Interestingly , spinal anesthesia was associated with a lower frequency of chronic pain , justifying prospect i ve study of spinal anesthesia for patients with a high risk for development of chronic postsurgical pain Objectives : To identify risk factors for postherpetic neuralgia ( PHN ) using a vali date d definition of this chronic neuropathic pain syndrome , to determine combinations of risk factors that identify patients with a high risk of developing PHN , and to examine the characteristics of patients with subacute herpetic neuralgia , that is , pain that persists beyond the acute phase of herpes zoster but that resolves before PHN can be diagnosed . Methods : The authors examined baseline and follow-up data from 965 herpes zoster patients enrolled within 72 hours of rash onset in two clinical trials of famciclovir . Results : Univariate and multivariate analyses indicated that older age , female sex , presence of a prodrome , greater rash severity , and greater acute pain severity made independent contributions to identifying which patients developed PHN . Patients with subacute herpetic neuralgia who did not develop PHN were significantly younger and had less severe acute pain than PHN patients but were significantly more likely to have severe and widespread rash than patients without persisting pain . Conclusions : The independent contributions to the prediction of PHN made by older age , female sex , presence of a prodrome , greater rash severity , and greater acute pain severity suggest that these risk factors reflect different mechanisms that each contribute to the development of PHN . Subacute herpetic neuralgia that does not progress to PHN may reflect peripheral tissue damage and inflammation caused by a particularly severe or widespread rash Seventy-one patients presenting with acute herpes zoster ophthalmicus were followed up for six months for a prospect i ve analysis of the natural history of the disease . Acute and chronic ocular complications , nasociliary nerve involvement , age , sex , rash , and pain were assessed , and the results are presented . Acute pain was measured by a visual analogue scale . Postherpetic neuralgia ( PHN ) was more likely in patients over 80 and in those who scored their pain highly at presentation . Duration of rash was longer in patients who developed PHN Output:	High- quality studies mainly assessed factors related to disease functions and structures .
MS21957	*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 This study is an integrated efficacy analysis of the five clinical trials of tositumomab and iodine-131 tositumomab in patients with relapsed or refractory low- grade , follicular , or transformed low- grade non-Hodgkin 's lymphoma ( NHL ) that result ed in the regulatory approval of the iodine-131 tositumomab by the US Food and Drug Administration . PATIENTS AND METHODS This integrated analysis included 250 patients . Patients received a single course of iodine-131 tositumomab . Responses were assessed by an independent panel of radiologists and oncologists . RESULTS Response rates in the five trials ranged from 47 % to 68 % ; complete response rates ranged from 20 % to 38 % . With a median follow-up of 5.3 years , the 5-year progression-free survival was 17 % . Eighty-one ( 32 % ) of 250 patients had a time to progression of > or = 1 year ( termed durable response population ) . For the durable response population , 44 % had not progressed at > or = 2.5 to > or = 9.5 years and had a median duration of response of 45.8 months . The median duration of complete response was not reached . The durable response population had many poor prognostic characteristics , including bone marrow involvement ( 41 % ) , bulky disease > or = 5 cm ( 49 % ) , and transformed histology ( 23 % ) . Forty-three percent of the patients had been treated with more than four prior therapies and 36 % had not responded to their most recent therapy . CONCLUSION The tositumomab and iodine-131 tositumomab therapeutic regimen produces high response rates in patients with relapsed or refractory low- grade , follicular , and transformed low- grade NHL , with a sizable subgroup of patients achieving long-term durable responses BACKGROUND The role of rituximab in combination with different CHOP ( cyclophosphamide , doxorubicin , vincristine , and prednisone)-like chemotherapy regimens in young patients with good-prognosis diffuse large-B-cell lymphoma remains to be defined . We aim ed to compare CHOP-like chemotherapy and rituximab with CHOP-like chemotherapy alone in these patients . METHODS 824 patients who were from 18 countries ; aged 18 - 60 years ; and who had no risk factors or one risk factor according to age-adjusted International Prognostic Index ( IPI ) , stage II-IV disease , or stage I disease with bulk were enrolled . These patients were r and omly assigned to six cycles of CHOP-like chemotherapy and rituximab ( n=413 ) or to six cycles of CHOP-like chemotherapy alone ( n=411 ) . Bulky and extranodal sites received additional radiotherapy . The primary endpoint was event-free survival ; secondary endpoints were response , progression under therapy , progression-free survival , overall survival , and frequency of toxic effects . Analyses were done by intention to treat and per protocol . This trial is registered at http://www . clinical trials.gov , NCT 00064116 . FINDINGS After a median follow-up of 34 months ( range 0.03 - 61 ) , patients assigned chemotherapy and rituximab had increased 3-year event-free survival compared with those assigned chemotherapy alone ( 79 % [ 95 % CI 75 - 83 ] vs 59 % [ 54 - 64 ] ; difference between groups 20 % [ 13 - 27 ] , log-rank p<0.0001 ) , and had increased 3-year overall survival ( 93 % [ 90 - 95 ] vs 84 % [ 80 - 88 ] ; difference between groups 9 % [ 3 - 13 ] , log-rank p=0.0001 ) . Event-free survival was affected by treatment group , presence of bulky disease , and age-adjusted IPI : after chemotherapy and rituximab , a favourable subgroup ( ie , IPI=0 , no bulk ) could be defined from a less-favourable subgroup ( ie , IPI=1 or bulk , or both ) . Groups did not differ in the frequency of adverse events . INTERPRETATION Rituximab added to six cycles of CHOP is an effective treatment for young patients with good-prognosis diffuse large-B-cell lymphoma . The definition of two prognostic subgroups allows for a more refined therapeutic approach for these patients BACKGROUND We conducted a multinational , r and omized study to compare radiotherapy alone with radiotherapy plus cetuximab , a monoclonal antibody against the epidermal growth factor receptor , in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck . METHODS Patients with locoregionally advanced head and neck cancer were r and omly assigned to treatment with high-dose radiotherapy alone ( 213 patients ) or high-dose radiotherapy plus weekly cetuximab ( 211 patients ) at an initial dose of 400 mg per square meter of body-surface area , followed by 250 mg per square meter weekly for the duration of radiotherapy . The primary end point was the duration of control of locoregional disease ; secondary end points were overall survival , progression-free survival , the response rate , and safety . RESULTS The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone ( hazard ratio for locoregional progression or death , 0.68 ; P=0.005 ) . With a median follow-up of 54.0 months , the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone ( hazard ratio for death , 0.74 ; P=0.03 ) . Radiotherapy plus cetuximab significantly prolonged progression-free survival ( hazard ratio for disease progression or death , 0.70 ; P=0.006 ) . With the exception of acneiform rash and infusion reactions , the incidence of grade 3 or greater toxic effects , including mucositis , did not differ significantly between the two groups . CONCLUSIONS Treatment of locoregionally advanced head and neck cancer with concomitant high-dose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck . ( Clinical Trials.gov number , NCT00004227 . It is unclear whether new treatment modalities have improved the survival of follicular lymphoma patients . Some data show that there has been no improvement in survival in the last 3 decades of the 20th century , whereas the results of recent retrospective studies suggest that evolving therapy has improved the outcome for follicular lymphoma patients 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 . BACKGROUND The monoclonal antibody 3H1 mimics the external structure of the carcinoembryonic antigen ( CEA ) . It therefore has the potential , via the anti-idiotypic network , to stimulate immune responses to CEA that may benefit colorectal cancer patients . PATIENTS AND METHODS A total of 630 patients with previously untreated metastatic colorectal cancer were r and omised in a 2:1 fashion to receive bolus 5-fluorouracil ( 5-FU ) and leucovorin ( LV ) plus either 3H1 ( n = 422 ) or placebo ( n = 208 ) . RESULTS The addition of 3H1 to 5-FU and LV did not result in increased toxicity . Survival for the full intent-to-treat population was 14.7 months for the 3H1 arm and 15.2 months for the placebo arm ( P = 0.80 ) . Anti-CEA antibody responses were observed in 70 % of patients treated with 3H1 . Patients with a negative CEA response had a median survival of 8.3 months ( 95 % CI 7.5 - 11.0 ) compared with patients with a strong response : median survival not reached ( P < 0.001 ) . CONCLUSION 3H1 is safe and effectively induces immune responses to CEA . Addition of 3H1 to 5-FU and LV was not shown to improve overall patient outcomes . However , improved survival in patients developing anti-CEA responses to 3H1 are provocative and should be studied in further clinical trials UNLABELLED Orthotopic liver transplantation ( OLT ) is the only curative therapy of HCC with underlying cirrhosis , but due to HCC metastasis and recurrence , its benefit is limited to a small population who meet the strict selection criteria . We previously reported that Licartin ( [ 131I ] mAb HAb18G/CD147 ) was safe and effective in treating HCC patients , and its antigen , HAb18G/CD147 , was closely related to HCC invasion and metastasis . Here , we reported a r and omized controlled trial to assess the post-OLT antirecurrence efficacy of Licartin in advanced HCC patients . We r and omized 60 post-OLT patients with HCC , who were at tumor stage 3/4 and outside the Milan criteria before OLT , into 2 groups . Three weeks after OLT , the treatment group received 15.4 MBq/kg of Licartin , while the control group received placebo intravenously for 3 times with an interval of 28 days . At 1-year follow-up , the recurrence rate significantly decreased by 30.4 % ( P = 0.0174 ) and the survival rate increased by 20.6 % ( P = 0.0289 ) in the treatment group , compared with those in the control group . For the control group versus the treatment group , the hazard ratio for recurrence was 3.60 ( 95 % confidence interval [ CI ] , 1.50 - 8.60 ) and that for death was 3.87 ( 95 % CI , 1.23 - 12.21 ) . Licartin treatment also result ed in an earlier decreased AFP level and a longer time of normal AFP level than placebo ( P = 0.0016 ) . No Licartin-related toxic effects were observed . CONCLUSION Licartin is a promising drug for preventing post-OLT tumor recurrence in advanced HCC patients excluded by the currently strict criteria for OLT . HAb18G/CD147 can be a good drug target The potential benefits of extended rituximab treatment have been investigated in a r and omized trial comparing the st and ard schedule with prolonged treatment in 202 patients with newly diagnosed or refractory/relapsed follicular lymphoma ( FL ) . All patients received st and ard treatment ( rituximab 375 mg/m(2 ) weekly x 4 ) . In 185 evaluable patients , the overall response rate was 67 % in chemotherapy-naive patients and 46 % in pretreated cases ( P < .01 ) . Patients responding or with stable disease at week 12 ( n = 151 ) were r and omized to no further treatment or prolonged rituximab administration ( 375 mg/m(2 ) every 2 months Output:	( 1 ) Many of the significant advances in cancer management in recent years have centered on the development and introduction of molecularly targeted therapies , such as monoclonal antibodies and tyrosine kinase inhibitors.(2 ) Despite targeted therapy that has clearly benefited and even cured certain patients ( eg , imatinib , trastuzumab ) , the ultimate goal of curing cancer , and the more immediate goal of replacing non-targeted chemotherapies with less toxic , targeted agents has yet to be achieved for most cancer patients .(3 ) Based on a systematic review of r and omized controlled trials , examples of significant benefits in selected cancers are provided:(a ) Non-Hodgkin 's lymphoma ( NHL ) - A large meta- analysis and several individual r and omised , controlled trials ( RCTs ) report that rituximab plus chemotherapy has a major survival advantage over chemotherapy alone in patients with NHL ; an overview of six clinical trials supports the survival benefit of rituximab plus chemotherapy.(b ) Renal cell carcinoma ( RCC ) - Temsirolimus or sunitinib has a significant survival benefit relative to interferon-alpha , and sorafenib carries such a benefit in patients resistant to st and ard therapy.(c ) Colorectal cancer ( CRC ) - An overview of three RCTs in metastatic CRC revealed that bevacizumab plus 5-fluorouracil/leucovorin possesses a significant survival advantage over 5-fluorouracil/leucovorin and irinotecan/5-fluorouracil/leucovorin.(d ) Non-small-cell lung cancer ( NSCLC ) - In refractory NSCLC , erlotinib significantly prolongs survival , particularly in nonsmokers , and gefitinib may have some utility in patients of Asian ethnicity.(e ) Head and neck squamous-cell carcinoma ( HNSCC ) - Cetuximab plus radiotherapy ( versus radiotherapy alone ) significantly improves locoregional control and survival ( hazard ratio [ HR ] 0.68 ; p = 0.005 ) without worsening radiotherapy-related toxicity
MS21958	*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: Prostate cancer incidence was prospect ively studied among 7999 men of Japanese ancestry who were first examined between 1965 and 1968 and then followed through 1986 . During this surveillance period , 174 incident cases of prostate cancer were recorded . Prostate cancer was not associated with any measure of socioeconomic status , including amount of education , type of occupation , and type of residence . There was also no relationship with the number of children , as a surrogate measure of sexual activity . Increased consumption of rice and tofu were both associated with a decreased risk of prostate cancer , while consumption of seaweeds was associated with an increased risk of prostate cancer . There was no relationship between prostate cancer and the intake of various nutrients , including total fat and total protein . Etiological implication s of these associations are discussed , but more research is needed on these dietary factors and the subsequent development of prostate cancer before any firm conclusions can be drawn Abstract Background : Calcium , phosphorus , fructose , and animal protein are hypothesized to be associated with prostate cancer risk , potentially via their influence on 1,25-dihydroxyvitamin D3 . We examined these nutrients and overall diet and prostate cancer risk in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study ( ATBC Study ) . Material s and methods : The ATBC Study was a r and omized 2 × 2 trial of alpha-tocopherol and beta-carotene on lung cancer incidence conducted among Finnish male smokers ; 27,062 of the men completed a food-use question naire at baseline , and comprise the current study population . There were 184 incident clinical ( stage 2–4 ) prostate cancer cases diagnosed between 1985 and 1993 . We used Cox proportional hazards models to examine associations between dietary intakes and prostate cancer . Results : We did not observe significant independent associations for calcium and phosphorus and prostate cancer risk . However , men with lower calcium and higher phosphorus intake had a multivariate relative risk of 0.6 ( 95 % CI 0.3–1.0 ) compared to men with lower intakes of both nutrients , adjusting for age , smoking , body mass index , total energy , education , and supplementation group . Of the other foods and nutrients examined , none was significantly associated with risk . Discussion : This study provides , at best , only weak evidence for the hypothesis that calcium and phosphorus are independently associated with prostate cancer risk , but suggests that there may be an interaction between these nutrients BACKGROUND Findings from early observational studies have suggested that the intake of dietary fat might be a contributing factor in the etiology of prostate cancer . However , the results from more recent prospect i ve studies do not support this hypothesis , and the possible association between different food sources of fat and prostate cancer risk also remains unclear . OBJECTIVE The objectives were to assess whether intakes of dietary fat , subtypes of fat , and fat from animal products were associated with prostate cancer risk . DESIGN This was a multicenter prospect i ve study of 142,520 men in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) . Dietary fat intake was estimated with the use of country-specific vali date d food question naires . The association between dietary fat and risk of prostate cancer was assessed by using Cox regression , stratified by recruitment center and adjusted for height , weight , smoking , education , marital status , and energy intake . RESULTS After a median follow-up time of 8.7 y , prostate cancer was diagnosed in 2727 men . There was no significant association between dietary fat ( total , saturated , monounsaturated , and polyunsaturated fat and the ratio of polyunsaturated to saturated fat ) and risk of prostate cancer . The hazard ratio for prostate cancer for the highest versus the lowest quintile of total fat intake was 0.96 ( 95 % CI : 0.84 , 1.09 ; P for trend = 0.155 ) . There were no significant associations between prostate cancer risk and fat from red meat , dairy products , and fish . CONCLUSION The results from this large multicenter study suggest that there is no association between dietary fat and prostate cancer risk itamin E supplements could V reduce prostate-cancer incidence and mortality by one-third in men who smoke , according to the results of a large primary -prevention trial in Finnish men . Prostate cancer is the fourth most common male cancer . As part of the Alpha-Tocopherol , Beta-Carotene ( ATBC ) study ( US National Cancer Institute and University of Helsinki , Finl and ) , more than 29 000 male smokers aged 50 - 69 years were r and omly assigned to receive 50 mg atocopherol , 20 mg P-carotene , both , or placebo daily for up to 8 years . At the end of the study , 246 new cases of prostate cancer and 62 deaths from the disease had occurred . Incidence was 32 % lower , and mortality 41 % lower , in men taking a-tocopherol , with or without P-carotene , than in those not taking the vitamin Nad Cancer Znst 1998 ; 90 : 440 - 46 ) . Men taking P-carotene had a 23 % . amin supplementation can be diffihigher incidence of , and 15 % higher cult to interpret , especially when mortality from , prostate cancer than there are multiple endpoints and no those not taking it . But these differences were not statistically significant . In addition , the investigators found that p-carotene nonsignificantly reduced the risk of prostate cancer in nondrinkers and increased the risk in drinkers , the risk rising with increasing strong a priori hypothesis . “ If the effect of a vitamin supplement is examined at , say , 20 cancer sites ” , says Franceschi , “ it is likely to appear protective at one site purely by chance . ” “ Studies with vitamin supplements are not a good basis for dietary advice ” , consumpDeserves further High dietary intakes of calcium and dairy products have been hypothesized to enhance prostate cancer risk , but available prospect i ve data regarding these associations are inconsistent . We examined dietary intakes of calcium and dairy products in relation to risk of prostate cancer in the Alpha-Tocopherol , Beta-Carotene ( ATBC ) Cancer Prevention Study , a cohort of 29,133 male smokers aged 50 - 69 years at study entry . Dietary intake was assessed at baseline using a vali date d 276-item food use question naire . Cox proportional hazards regression was used to adjust for known or suspected risk factors for prostate cancer . During 17 years of follow-up , we ascertained 1,267 incident cases of prostate cancer . High versus low intake of dietary calcium was associated with a marked increase in prostate cancer risk . The multivariate relative risk ( RR ) of prostate cancer for > or = 2,000 mg/day compared to < 1,000 mg/day of calcium intake was 1.63 ( 95 % confidence interval ( CI ) , 1.27 - 2.10 ; p trend < 0.0001 ) . Total dairy intake was also positively associated with risk of prostate cancer . The multivariate RR of prostate cancer comparing extreme quintiles of intake was 1.26 ( 95 % CI , 1.04 - 1.51 ; p trend = 0.03 ) . However , no association with total dairy intake remained after we adjusted for calcium ( p trend = 0.17 ) . Findings were similar by stage and grade of prostate cancer . The results from this large prospect i ve study suggest that intake of calcium or some related component contained in dairy foods is associated with increased prostate cancer risk BACKGROUND Prostate cancer is a disease with a complex etiology . Oxidative stress has been implicated in its pathogenesis ; however , few prospect i ve studies have investigated the association between an oxidative stress/balance score and risk of prostate cancer . METHODS We investigated associations between an oxidative balance score , calculated as the summation of individual scores obtained from five pro-oxidative and eight anti-oxidative exposures , as well as each individual constituent of the score and risks of prostate cancer overall , and by clinical characteristics , in a case-cohort study ( 661 cases and 1864 subcohort ) nested within the Canadian Study of Diet , Lifestyle , and Health cohort . Men in the lowest quintiles of each pro-oxidant exposure received a score of four ( the highest score ) , while those in the highest quintile received a score of zero ( the lowest score ) . In contrast , scoring for all anti-oxidants was performed in the opposite way . Total oxidative balance score was calculated by summating all individual scores of pro- and anti-oxidative variables , with higher values indicating a higher antioxidant status . RESULTS The average oxidative balance score was similar between prostate cancer cases and men in the subcohort : 25.2 and 25.3 , respectively . There was no association between oxidative balance score and overall risk of prostate cancer with hazard ratios ( HRs ) of 1.00 , 1.02 , 1.03 , 0.97 and 1.01 for increasing quintiles of the score ( p-trend=0.71 ) . There were also no associations for non-advanced or advanced disease , or when analysis was restricted to incident cases that arose after two years of follow-up ( n=508 ) . In general constituents of the score were not associated with prostate cancer , except for red meat intake ( HR=1.44 ; 95%CI 1.06 - 1.95 comparing Q5 vs. Q1 ) and lycopene ( HRs of 0.7 - 0.8 for increasing quintiles ) . CONCLUSION Our findings do not support an association between oxidative balance score and risks of overall prostate cancer or advanced disease BACKGROUND The strong correlation between national consumption of fat and national rate of mortality from prostate cancer has raised the hypothesis that dietary fat increases the risk of this malignancy . Case-control and cohort studies have not consistently supported this hypothesis . PURPOSE We examined prospect ively the relationship between prostate cancer and dietary fat , including specific fatty acids and dietary sources of fat . We examined the relationship of fat consumption to the incidence of advanced prostate cancer ( stages C , D , or fatal cases ) and to the total incidence of prostate cancer . METHODS We used data from the Health Professionals Follow-up Study , which is a prospect i ve cohort of 51529 U.S. men , aged 40 through 75 , who completed a vali date d food-frequency question naire in 1986 . We sent follow-up question naires to the entire cohort in 1988 and 1990 to document new cases of a variety of diseases and to up date exposure information . As of January 31 , 1990 , 300 new cases of prostate cancer , including 126 advanced cases , were documented in 47855 participants initially free of diagnosed cancer . The Mantel-Haenszel summary estimator was used to adjust for age and other potentially confounding variables . Multiple logistic regression was used to estimate relative risks ( RRs ) when controlling simultaneously for more than two covariates . RESULTS Total fat consumption was directly related to risk of advanced prostate cancer ( age- and energy-adjusted RR = 1.79 , with 95 % confidence interval [ CI ] = 1.04 - 3.07 , for high versus low quintile of intake ; P [ trend ] = .06 ) . This association was due primarily to animal fat ( RR = 1.63 ; 95 % CI = 0.95 - 2.78 ; P [ trend ] = .08 ) , but not vegetable fat . Red meat represented the food group with the strongest positive association with advanced cancer ( RR = 2.64 ; 95 % CI = 1.21 - 5.77 ; P = .02 ) . Fat from dairy products ( with the exception of butter ) or fish was unrelated to risk . Saturated fat , monounsaturated fat , and alpha-linolenic acid , but not linoleic acid , were associated with advanced prostate cancer risk ; only the association with alpha-linolenic acid persisted when saturated fat , monounsaturated fat , linoleic acid , and alpha-linolenic acid were modeled simultaneously ( multivariate RR = 3.43 ; 95 % CI = 1.67 - 7.04 ; P [ trend ] = .002 ) . CONCLUSION The results support the hypothesis that animal fat , especially fat from red meat , is associated with an elevated risk of advanced prostate cancer . IMPLICATION S These findings support recommendations to lower intake of meat to reduce the risk of prostate cancer . The potential roles of carcinogens formed in cooking animal fat and of alpha-linolenic acid in the progression of prostate cancer need to be explored CONTEXT The most recent summary of the European Association of Urology ( EAU ) guidelines on prostate cancer ( PCa ) was published in 2011 . OBJECTIVE To present a summary of the 2013 version of the EAU guidelines on screening , diagnosis , and local treatment with curative intent of clinical ly organ-confined PCa . EVIDENCE ACQUISITION A literature review of the new data emerging from 2011 to 2013 has been performed by the EAU PCa guideline group . The guidelines have been up date d , and levels of evidence and grade s of recommendation have been added to the text based on a systematic review of the literature , which included a search of online data bases and bibliographic review s. EVIDENCE SYNTHESIS A full version of the guidelines is available at the EAU office or online ( www.uroweb.org ) . Current evidence is insufficient to warrant widespread population -based screening by prostate-specific antigen ( PSA ) for PCa . Systematic Output:	Subgroup and sensitively analyses showed consistent results . Conclusion Little evidence from published cohort studies supports the statement that total fat , saturated fat or unsaturated fat intake increases the risk for Pca or advanced stage Pca
MS21959	*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 To compare the frequencies , concentrations , and antimicrobial susceptibilities of vaginal microbes isolated from women with bacterial vaginosis ( BV ) before and after therapy , 119 nonpregnant women aged 18 to 45 with clinical and Gram stain evidence of BV were r and omized to receive intravaginal clindamycin or metronidazole . Vaginal swabs were collected at baseline and 7 to 12 days , 35 to 45 days , and 70 to 90 days following therapy for quantitative vaginal culture . For the 99 women completing all four visits , statistical analyses were performed comparing differences in vaginal microflora between the two treatment arms and between visits in the same treatment group . Antimicrobial susceptibility testing using the agar dilution method was performed for anaerobic gram-negative rods . Although both therapies result ed in decreased colonization by Gardnerella vaginalis and Mycoplasma hominis , only metronidazole treatment result ed in a significant decrease in the frequency and concentration of Prevotella bivia and black-pigmented Prevotella species . Of the 865 anaerobic gram-negative rods evaluated for susceptibility , only 3 ( 0.3 % ) were resistant to metronidazole , whereas clindamycin resistance increased significantly for P. bivia and black-pigmented anaerobic gram-negative rods persisting following clindamycin therapy . Clindamycin-resistant sub population s of P. bivia and black-pigmented Prevotella species emerged 7 to 12 days after therapy even among women colonized initially by clindamycin-susceptible strains . These resistant sub population s persisted at high frequencies ( 42 to 50 % ) 70 to 90 days following therapy . The two topical agents for treatment of BV have differing microbiologic effects on the vaginal microflora . The emergence of clindamycin-resistant anaerobic gram-negative rods following therapy is of concern SUMMARY Objective : We evaluated the efficacy and tolerability of a new chlorhexidine-based bioadhesive vaginal gel ( Clomirex * ) in women with vaginal infections . Study design and subjects : A total of 90 non-pregnant women with vaginal infections of both bacterial ( bacterial vaginosis : BV ) or fungal ( vaginal c and idiasis VC ) origin , were enrolled in the study : a r and omised , controlled , 4-week , multicentre trial . Patients were r and omly treated with either chlorhexidine 0.5 % vaginal gel ( CHX-VG ) , 2.5 g or with metronidazole vaginal tablets 500 mg ( M ) or clotrimazole ( CL ) vaginal cream , depending on aetiology of the infection , daily for 7 days ( treatment phase ) in a 2:1 ratio . A total of 45 women had a diagnosis of BV and 45 a diagnosis of VC . Sixty women were treated with CHX-VG , 15 with M and 15 with CL . All patients were followed for an additional 3 weeks without treatments ( follow-up phase ) . For women with BV , clinical cure rate was defined as the disappearance of the following signs and symptoms : homogenous vaginal discharge ; presence of ≥ 2 or more clue cells at the wet mount microscopy ; a vaginal pH > 4.7 and a positive whiff test . For women with VC , clinical cure rate was defined as a resolution of signs and symptoms plus absence of hyphae , pseudohyphae and blastospores on 10 % KOH wet mount microscopy . Clinical cure rate was assessed at the end of the study ( week 4 ) by an investigator unaware of the patient 's treatment allocation . Results : At week 4 , in women with BV , 28 out of 30 ( 93 % ) women in the CHX-VG group were clinical ly cured in comparison with 11 out of 15 ( 74 % ) in the M group ( p = 0.3 ) . In women with VC , 26 out of 30 ( 86.6 % ) women in the CHX-VG group were clinical ly cured in comparison with 13 out of 15 ( 86 % ) in the CL group ( p = 0.5 ) . Tolerability was good and very good in 90 % of the CHX-VG patients . Six women ( 10 % ) complained of a mild transient burning sensation after CHX-VG vaginal application . No serious adverse events were observed during the trial in all treated groups . No women presented with vaginal discharge after treatment . Conclusion : These results demonstrate that in the short term , this CHX-VG is an effective treatment for both bacterial and mycotic vaginal infections . Further clinical trials are warranted to evaluate the efficacy and tolerability profile of this new chlorhexidine vaginal gel on a long-term basis and in reducing recurrency rate of vaginal infections In a study of 100 women with non-specific vaginitis , characterised by a vaginal discharge which was malodorous and pruritic in most cases and caused dyspareunia and dysuria in some , Gardnerella vaginalis was isolated in 46 % of patients . When present , G vaginalis was significantly associated with Mycoplasma hominis and Bacteroides species . Isolation of G vaginalis was unrelated to the presenting symptoms . Treatment with povidone-iodine pessaries for two weeks produced no pronounced benefit , either clinical ly or microbiologically , compared with a placebo . Nevertheless , 68 % of all patients followed reported improvement four weeks after the start of treatment . The findings suggest that G vaginalis is one cause of non-specific vaginitis , which is more likely to be seen in women using oral contraceptives and is usually cured spontaneously Bacterial vaginosis ( BV ) is a common cause of abnormal malodorous vaginal discharge and can be frustrating to manage in its recurrent form . Metronidazole is the st and ard treatment , but is unacceptable to many women when given repeatedly . Results of treating recurrent BV using a single vaginal washout with 3 % hydrogen peroxide are analysed . A total of 30 symptomatic women with clinical ly confirmed recurrent BV in the absence of other genital infections were recruited after informed consent . Hydrogen peroxide ( 3 % ) was instilled into the vagina , left for 3 minutes and drained . Re assessment was at 3 weeks after treatment . A total of 23 women completed the study . Symptoms cleared completely in 78 % ( 18/ 23 ) , improved in 13 % ( 3/23 ) and remained unchanged in 9 % ( 2/23 ) . All the 3 women with improved symptoms had a mild vaginal discharge , but only one of them was still able to perceive the malodour . The amine test was negative in all 23 women including the 2 ( 9 % ) who felt no change in their symptoms following treatment . Mixed anaerobes isolated in all women before treatment were not re-isolated , and microscopy did not show ' clue cells ' in the vaginal discharge following treatment . Vaginal acidity was restored to normal in all but one ( 96 % ) . No side-effects were observed in the treated women . Hydrogen peroxide ( 3 % ) used as a single vaginal wash was as effective as any other agent in current use in clearing the vaginal malodour of bacterial vaginosis at 3 weeks after treatment OBJECTIVE This study was undertaken to evaluate antimicrobial susceptibility of vaginal anaerobic bacteria before and after treatment of bacterial vaginosis . STUDY DESIGN A r and omized clinical trial of 119 nonpregnant women with bacterial vaginosis receiving either intravaginal metronidazole for 5 days or clindamycin for 3 days was performed . Women had 1 baseline and 3 follow-up visits at which quantitative vaginal cultures were performed . Anaerobic isolates underwent antimicrobial susceptibility testing . RESULTS Complete susceptibility data was available on 95 women ( 47 metronidazole and 48 clindamycin ) . Of 1059 anaerobic bacterial isolates , less than 1 % demonstrated resistance to metronidazole . In contrast , 17 % demonstrated baseline clindamycin resistance , and 53 % demonstrated resistance to clindamycin after therapy . Women exposed to clindamycin ( but not metronidazole ) had high frequencies ( 80 % ) of clindamycin-resistant anaerobic bacteria that persisted for 90 days after treatment . CONCLUSION Treatment of bacterial vaginosis with clindamycin is associated with marked evidence of antimicrobial resistance among vaginal anaerobic bacteria . This may increase the vaginal reservoir of macrolide-resistant bacteria This r and omised , double-blind , multicentric clinical study compared the efficacy and tolerability of the two vaginal antiseptics , 10 mg dequalinium chloride ( CAS 522 - 51 - 0 , Fluomycin N ) and 200 mg povidone iodine ( CAS 25655 - 41 - 8 ) , in a parallel-group design . A total of 180 patients with vaginal infections of varying etiology participated in this study ( bacterial vaginosis , fluor vaginalis , vulvo-vaginal c and idiasis , trichomoniasis ) . Patients were r and omly allocated to one of the two treatment groups and were treated once per day for 6 days . Control examinations took place 5 to 7 days after the end of treatment , and 3 to 4 weeks after the first control examination . The total symptoms score , a summary score for the clinical symptoms , discharge , burning , pruritus , redness of vulva/vagina , was defined as primary efficacy parameter . The treatments at the first control examination were compared in the full analysis set using the Wilcoxon-Mann-Whitney U-test , 2-sided , thereby proving equivalence of both treatments at the 5 % level . Both treatments strongly improved the symptoms of vaginal infections both on short-term and long-term follow-up . Descriptive analysis of the secondary parameters , vaginal pH , degree of purity of the vaginal flora , and number of lactobacilli in the wet mounts , supported the comparable efficacy of both therapies to restore the vaginal milieu . Analysis of the diagnostic subgroups indicated that irrespective of the diagnosis , both treatments improved the efficacy criteria as observed for the entire population . The global assessment of the therapeutic efficacy by investigators and patients supported the results of the efficacy analysis with good to very good ratings in 70 - 90 % of the cases . A good tolerability of both preparations was observed in this study with a low number of adverse events in the test group ( 5.8 % ) OBJECTIVE At the present the clinical treatment of choice of bacterial vaginosis ( BV ) is the use of systemic or local metronidazole or clindamycin . Aim of the study was to evaluate the efficacy and tolerability of a single dose of gynaecologic solution , Polyhexamethylene Biguanide ( PHMB ) , Monogin , in the treatment of BV in comparison to a 7-days treatment with clindamycin vaginal cream . STUDY DESIGN This multicenter , r and omized , single-blind , parallel-group study enrolled 740 patients with BV infections . Treatment consisted of either a single intravaginal dose of PHMB or 7 daily doses of Clindamycin . Efficacy and safety were assessed 21 - 30 days after the start of treatment . The efficacy endpoints were Investigator Cure , Clinical Cure ( a composite of all 4 Amsel 's criteria and investigator Cure ) , Nugent Cure ( Nugent score < 4 ) , and therapeutic cure ( a composite of clinical cure and Nugent Cure ) . Resolution of individual Amsel 's criteria was also evaluated . Any adverse event of the treatment has been monitored throughout the study . RESULTS No significant differences has been reported in cure rates between the PHMB and Clindamycin treatment groups in Investigator Cure ( P = 0.702 ) , Clinical Cure ( P = 0.945 ) , Nugent Cure ( P = 0.788 ) , or Therapeutic Cure ( P = 0.572 ) . Results were also similar for 3 of 4 and 2 of 4 Amsel 's criteria and for each individual Amsel 's criterion ( all P-values > 0.200 ) . Ninety-five percent confidence intervals for each endpoint were consistent with equivalence between the 2 products . There was no significant difference between the treatment groups in the incidence of treatment-emergent adverse events ( P = 0.386 ) . CONCLUSIONS A single dose , of PHMB gynaecologic solution ( Monogin ) is equivalent in safety and efficacy to a 7-dose regimen of Clindamycin vaginal cream in the treatment of bacterial vaginosis . Futhermore the compliance as been reported to be higher for the single-dose treatment with PHMB than with 7-days treatment with Clindamycin Povidone-iodine pessaries ( Betadine vaginal pessaries ) containing 200 mg of povidone-iodine ( PVP-I ) in a water soluble base , are a widely used gynaecological preparation for treatment Output:	There is insufficient evidence at present to advocate the use of these agents , although some studies suggest that some antiseptics may have equal efficacy compared to clindamycin or metronidazole .
MS21960	*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 explore the causes of failure to activate the rapid response system ( RRS ) . The organisation has a recognised incidence of staff failing to act when confronted with a deteriorating patient and leading to adverse outcomes . Design A multi- method study using the following : a point prevalence survey to determine the incidence of abnormal simple bedside observations and activation of the rapid response team by clinical staff ; a prospect i ve audit of all patients experiencing a cardiac arrest , unplanned intensive care unit admission or death over an 8-week period ; structured interviews of staff to explore cognitive and sociocultural barriers to activating the RRS . Setting Southern Health is a comprehensive healthcare network with 570 adult in-patient beds across four metropolitan teaching hospitals in the south-eastern sector of Melbourne . Measurements Frequency of physiological instability and outcomes within the in-patient hospital population . Qualitative data from staff interviews were thematically coded . Results The incidence of physiological instability in the acute adult population was 4.04 % . Nearly half of these patients ( 42 % ) did not receive an appropriate clinical response from the staff , despite most ( 69.2 % ) recognising their patient met physiological criteria for activating the RRS , and being ‘ quite ’ , or ‘ very ’ concerned about their patient ( 75.8 % ) . Structured interviews with 91 staff members identified predominantly sociocultural reasons for failure to activate the RRS . Conclusions Despite an organisational commitment to the RRS , clinical staff act on local cultural rules within the clinical environment that are usually not explicit . Better underst and ing of these informal rules may lead to more appropriate activation of the RRS Background Increasing dem and s on general practice to manage chronic disease may warrant organisational change at the practice level . Staff 's readiness for organisational change can act as a facilitator or barrier to implementing interventions aim ed at organisational change . Objectives To explore general practice staff readiness for organisational change and its association with staff and practice s characteristics . Methods This is a cross-sectional study of practice s in three Australian states involved in a r and omised control trial on the effectiveness of an intervention to enhance the role of non-general practitioner staff in chronic disease management . Readiness for organisational change , job satisfaction and practice characteristics were assessed using question naires . Results 502 staff from 58 practice s completed question naires . Practice characteristics were not associated with staff readiness for change . A multilevel regression analysis showed statistically significant associations between staff readiness for organisational change ( range 1 to 5 ) and having a non- clinical staff role ( vs general practitioner ; B=−0.315 ; 95 % CI −0.47 to −0.16 ; p<0.001 ) , full-time employment ( vs part-time ; B=0.175 , 95 % CI 0.06 to 0.29 ; p<0.01 ) and lower job satisfaction ( B=−0.277 , 95 % CI −0.40 to −0.15 ; p<0.001 ) . Conclusions The results suggest that different approaches are needed to facilitate change which addresses the mix of practice staff . Moderately low job satisfaction may be an opportunity for organisational change BACKGROUND Surgery has become an integral part of global health care , with an estimated 234 million operations performed yearly . Surgical complications are common and often preventable . We hypothesized that a program to implement a 19-item surgical safety checklist design ed to improve team communication and consistency of care would reduce complications and deaths associated with surgery . METHODS Between October 2007 and September 2008 , eight hospitals in eight cities ( Toronto , Canada ; New Delhi , India ; Amman , Jordan ; Auckl and , New Zeal and ; Manila , Philippines ; Ifakara , Tanzania ; London , Engl and ; and Seattle , WA ) representing a variety of economic circumstances and diverse population s of patients participated in the World Health Organization 's Safe Surgery Saves Lives program . We prospect ively collected data on clinical processes and outcomes from 3733 consecutively enrolled patients 16 years of age or older who were undergoing noncardiac surgery . We subsequently collected data on 3955 consecutively enrolled patients after the introduction of the Surgical Safety Checklist . The primary end point was the rate of complications , including death , during hospitalization within the first 30 days after the operation . RESULTS The rate of death was 1.5 % before the checklist was introduced and declined to 0.8 % afterward ( P=0.003 ) . Inpatient complications occurred in 11.0 % of patients at baseline and in 7.0 % after introduction of the checklist ( P<0.001 ) . CONCLUSIONS Implementation of the checklist was associated with concomitant reductions in the rates of death and complications among patients at least 16 years of age who were undergoing noncardiac surgery in a diverse group of hospitals Background Service development innovation in health technology and practice is viewed as a pressing need within the field of mental health yet is relatively poorly understood . Macro-level theories have been criticised for their limited explanatory power and they may not be appropriate for underst and ing local and fine-grained uncertainties of services and barriers to the sustainability of change . This study aim ed to identify context ual influences inhibiting or promoting the acceptance and integration of innovations in mental health services in both National Health Service ( NHS ) and community setting s. Methods A comparative study using qualitative and case study data collection methods , including semi-structured interviews with key stakeholders and follow-up telephone interviews over a one-year period . The analysis was informed by learning organisation theory . Drawn from 11 mental health innovation projects within community , voluntary and NHS setting s , 65 participants were recruited including service users , commissioners , health and non-health professionals , managers , and caregivers . The methods deployed in this evaluation focused on process- outcome links within and between the 11 projects . Results Key barriers to innovation included resistance from corporate departments and middle management , complexity of the innovation , and the availability and access to re sources on a prospect i ve basis within the host organisation . The results informed the construction of a proposed model of innovation implementation within mental health services . The main components of which are context , process , and outcomes . Conclusions The study produced a model of conducive and impeding factors drawn from the composite picture of 11 innovative mental health projects , and this is discussed in light of relevant literature . The model provides a rich agenda to consider for services wanting to innovate or adopt innovations from elsewhere . The evaluation suggested the importance of study ing innovation with a focus on context , process , and outcomes Background Despite recent high- quality evidence for their cost-effectiveness , thiazides are underused for controlling hypertension . The goal of this study was to design and test a practice -based intervention aim ed at increasing the use of thiazide-based antihypertensive regimens . Methods This quasi-experimental study was carried out in general medicine ambulatory practice s of a large , academically-affiliated Veterans Affairs hospital . The intervention group consisted of the practitioners ( 13 staff and 215 trainees ) , nurses , and patients ( 3,502 ) of the teaching practice ; non-r and omized concurrent controls were the practitioners ( 31 providers ) and patients ( 18,292 ) of the non-teaching practice s. Design of the implementation intervention was based on Rogers ' Diffusion of Innovations model . Over 10.5 months , intervention teams met weekly or biweekly and developed and disseminated informational material s among themselves and to trainees , patients , and administrators . These teams also review ed summary electronic-medical-record data on thiazide use and blood pressure ( BP ) goal attainment . Outcome measures were the proportion of hypertensive patients prescribed a thiazide-based regimen , and the proportion of hypertensive patients attaining BP goals regardless of regimen . Thirty-three months of time-series data were available ; statistical process control charts , change point analyses , and before-after analyses were used to estimate the intervention 's effects . Results Baseline use of thiazides and rates of BP control were higher in the intervention group than controls . During the intervention , thiazide use and BP control increased in both groups , but changes occurred earlier in the intervention group , and primary change points were observed only in the intervention group . Overall , the pre-post intervention difference in proportion of patients prescribed thiazides was greater in intervention patients ( 0.091 vs. 0.058 ; p = 0.0092 ) , as was the proportion achieving BP goals ( 0.092 vs. 0.044 ; p = 0.0005 ) . At the end of the implementation period , 41.4 % of intervention patients were prescribed thiazides vs. 30.6 % of controls ( p < 0.001 ) ; 51.6 % of intervention patients had achieved BP goals vs. 44.3 % of controls ( p < 0.001 ) . Conclusion This multi-faceted intervention appears to have result ed in modest improvements in thiazide prescribing and BP control . The study also demonstrates the value of electronic medical records for implementation research , how Rogers ' model can be used to design and launch an implementation strategy , and how all members of a clinical microsystem can be involved in an implementation effort Background The Promoting Action on Research Implementation in Health Services framework , or PARIHS , is a conceptual framework that posits key , interacting elements that influence successful implementation of evidence -based practice s. It has been widely cited and used as the basis for empirical work ; however , there has not yet been a literature review to examine how the framework has been used in implementation projects and research . The purpose of the present article was to critically review and synthesize the literature on PARIHS to underst and how it has been used and operationalized , and to highlight its strengths and limitations . Methods We conducted a qualitative , critical synthesis of peer- review ed PARIHS literature published through March 2009 . We synthesized findings through a three-step process using semi-structured data abstract ion tools and group consensus . Results Twenty-four articles met our inclusion criteria : six core concept articles from original PARIHS authors , and eighteen empirical articles ranging from case reports to quantitative studies . Empirical articles generally used PARIHS as an organizing framework for analyses . No studies used PARIHS prospect ively to design implementation strategies , and there was generally a lack of detail about how variables were measured or mapped , or how conclusions were derived . Several studies used findings to comment on the framework in ways that could help refine or vali date it . The primary issue identified with the framework was a need for greater conceptual clarity regarding the definition of sub-elements and the nature of dynamic relationships . Strengths identified included its flexibility , intuitive appeal , explicit acknowledgement of the outcome of ' successful implementation , ' and a more expansive view of what can and should constitute ' evidence . ' Conclusions While we found studies reporting empirical support for PARIHS , the single greatest need for this and other implementation models is rigorous , prospect i ve use of the framework to guide implementation projects . There is also need to better explain derived findings and how interventions or measures are mapped to specific PARIHS elements ; greater conceptual discrimination among sub-elements may be necessary first . In general , it may be time for the implementation science community to develop consensus guidelines for reporting the use and usefulness of theoretical frameworks within implementation studies Objective Implementation of a surgical checklist depends on many organisational factors and on socio-cultural patterns . The objective of this study was to identify barriers to effective implementation of a surgical checklist and to develop a best use strategy . Setting 18 cancer centres in France . Design The authors first assessed use compliance and completeness rates of the surgical checklist on a r and om sample of 80 surgical procedures performed under general or loco-regional anaesthesia in each of the 18 centres . They then developed a typology of the organisational and cultural barriers to effective checklist implementation and defined each barrier 's contents using data from collective and semi-structured individual interviews of key staff , the results of an email question naire sent to the 18 centres , and direct observations over 20 h in two centres . Results The study consisted of 1440 surgical procedures , 1299 checklists , and 28 578 items . The mean compliance rate was 90.2 % ( 0 , 100 ) . The mean completion rate was 61 % ( 0 , 84 ) . 11 barriers to effective checklist implementation were identified . Their incidence varied widely across centres . The main barriers were duplication of items within existing checklists ( 16/18 centres ) , poor communication between surgeon and anaesthetist ( 10/18 ) , time spent completing the checklist for no perceived benefit , and lack of underst and ing and timing of item checks ( 9/18 ) , ambiguity ( 8/18 ) , unaccounted risks ( 7/18 ) and a time-honoured hierarchy ( 6/18 ) . Conclusions Several of the barriers to the successful implementation of the surgical checklist depended on organisational and cultural factors within each centre . The authors propose a strategy for change for checklist design , use and assessment , which could be used to construct a feedback loop for local team organisation and national initiatives Background Data of the German Competence Network for Community-Acquired Pneumonia showed a gap between the recommendations of the national guideline for management of community-acquired pneumonia ( CAP ) and the routine care . We developed and evaluated an implementation strategy to improve the quality of care of patients with CAP . Method A prospect i ve , r and omised , controlled trail was conducted within CAPNETZ . In four local clinical centres ( LCC ) , the guideline was implemented by different strategies . The other four LCC served as control group . Indicators for guideline adherence comprised initial site of treatment , initial antibiotic treatment and duration of antibiotic treatment . As patient-related factors , we assessed the effect of guideline implementation on 30-day mortality and length of hospital stay . Results Active guideline implementation yielded an increased proportion of guideline adherence to the length of antibiotic treatment in out patients ( + 9.2 % ) , the recommended antibiotic treatment ( + Output:	Obstacles in implementation are the mirror image of these : for example , when people fail to prepare , have insufficient capacity for implementation or when the setting is resistant to change , then care quality is at risk , and patient safety can be compromised .
MS21961	*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 In delayed extracorporeal shock wave lithotripsy ( ESWL ) treatment , increasing stone impaction is associated with delayed stone clearance . Whether colic patients treated by rapid ESWL have the same time to stone clearance as noncolic patients , which supports the thesis that stones in both groups are nonimpacted , has not been investigated yet , and was the objective of this study . METHODS A total of 82 patients were prospect ively enrolled and treated with piezoelectric ESWL for a solitary proximal ureteral stone . Of these , 56 patients experienced at least one colic episode compared with 26 noncolic patients . Hydronephrosis has been assessed with the use of ultrasound and intravenous urography ( IVU ) . Time to stone clearance after the first ESWL and stone-free rates after a follow-up period of 3 mo were recorded . RESULTS In colic and noncolic patients , mean stone size was 7.8 mm ( p=0.7 ) . Ultrasound-detected hydronephrosis was present in 88 % versus 39 % ( p<0.0001 ) , whereas IVU-detected hydronephrosis was present in 60 % versus 7.7 % ( p=0.0001 ) . Mean number of impulses applied was 8000+/-4000 versus 6700+/-3400 ( p=0.1 ) . Mean time to stone clearance was 9.5+/-12.1 d versus 4.6+/-3.8 d ( p=0.1 ) . Colic and noncolic patients were considered as treatment success in 83 % and 81 % after 3 mo of follow-up ( p=0.9 ) . CONCLUSIONS Treatment outcome and time to stone clearance after rapid ESWL in colic patients compared with noncolic patients is comparable and independent of concomitant hydronephrosis . This finding suggests an absence of significant impaction in proximal ureteral stones treated within 24h after a first colic episode , enforcing the concept of performing rapid ESWL in patients harbouring proximal ureteral stones PURPOSE We evaluated the effect of the alpha-blocker tamsulosin on stone clearance , analgesic requirements and steinstrasse in shock wave lithotripsy for solitary renal and ureteral calculus . MATERIAL S AND METHODS A prospect i ve , double-blind , r and omized placebo controlled study was performed during 1 year involving 60 patients with a solitary renal or ureteral calculus undergoing shock wave lithotripsy . The control group ( 30 ) received 0.4 mg tamsulosin and the study group ( 30 ) received placebo daily until stone clearance or for a maximum of 30 days . An oral preparation of dextropropoxyphene hydrochloride and acetaminophen was the analgesic used on an on-dem and basis . The parameters assessed were stone size , position , clearance time , effect on steinstrasse and analgesic requirement . RESULTS The overall clearance rate was 96.6 % ( 28 of 29 ) in the study group and 79.3 % ( 23 of 29 ) in the control group ( p = 0.04 ) . With larger stones 11 to 24 mm the difference in the clearance rate was significant ( p = 0.03 ) but not so with the smaller stones 6 to 10 mm ( p = 0.35 ) . The average dose of analgesic used was lower with tamsulosin than with controls , without statistical significance . Steinstrasse resolved spontaneously in the tamsulosin group whereas 25 % ( 2 of 8) required intervention in the placebo group . There was no difference between the 2 groups with regard to age , stone size or location . CONCLUSIONS The alpha-blocker tamsulosin seemed to facilitate stone clearance , particularly with larger stones during shock wave lithotripsy for renal and ureteral calculus . It also appeared to improve the outcome of steinstrasse . Tamsulosin may have a potential role in routine shock wave lithotripsy Background : Alpha – 1 blockers decrease the tension and release the spasm of smooth muscles and thus lessen the obstruction and irritation symptoms in the lower urinary tract ( LUTS ) . They make a faster passing of calculi from the terminal part of the ureters possible . Objectives : The goal of this study was to objective ly assess the improvement of difficulties caused by obstructions in ureterolithiasis localized in the lower part of the ureters of 104 r and omly chosen patients ( pts . ) in a double-blind study . Methods : During a period of 2 and half years ( June 1999–January 2002 ) 104 pts . suffering from ureterolithiasis of the lower urinary tract were treated and observed . Patients were divided into two groups : A ( n:53 ; later only 51 were evaluated ) which was subjected to st and ard treatment and group B ( n:51 ) where the st and ard treatment was supplemented by the alpha – 1 blocker . As alpha – 1 blocker one capsule of Tamsulosin /OMNIC 0.4 / was administered daily . Results : With alpha – 1 blocker , we have registered a more speedy passing of calculi from the terminal parts of ureters in 17.6 % of pts . Recurrence of renal colics was less frequent and occurred in one of eight pts . as compared with group A ( without the alpha – 1 blocker ) where a recurrence of the renal colic was observed in about every fifth pts . In group A ( n:51 ) , 62.8 % of the pts . passed the calculi , whereas in group B ( n:51 ) , where st and ard treatment was supplemented by the administration of the alpha – 1 blocker Tamsulosin , this percentage increased to 80.4 % . Conclusion : The treatment by alpha – 1 blockers considerably decreased not only LUTS but also helped to accelerate the passing of minor calculi from the terminal parts of the ureters of 80.4 % of pts . It seems that alpha – 1 blockers potentiate the spasmoanalgetic action of drugs used in st and ard methods of treatment OBJECTIVES To design a r and omized , no-treatment , controlled , prospect i ve study to determine whether the administration of tamsulosin , as adjunctive medical therapy , increases the efficacy of one extracorporeal shock wave lithotripsy ( ESWL ) session to treat renal stones and decreases the use of analgesic drugs after the procedure . METHODS A total of 130 patients underwent a single ESWL session to treat solitary radiopaque renal stones 4 to 20 mm in diameter . After treatment , all patients were r and omly assigned to receive our st and ard medical therapy alone ( controls ) or in association with 0.4 mg tamsulosin daily for a maximum of 12 weeks . All 130 patients were followed up for 3 months or until an alternative treatment was given . RESULTS Of the 130 patients , 78.5 % of those receiving tamsulosin and 60 % of controls had achieved clinical success at 3 months ( P = 0.037 ) . When we stratified patients according to stone size , for those with a stone size larger than 10 mm , the success rate was significantly greater in the tamsulosin group ( P = 0.028 ) . Renoureteral colic occurred in 76.9 % of patients treated with st and ard therapy but in only 26.1 % of those receiving tamsulosin ( P < 0.001 ) . The mean cumulative diclofenac dose was 375 mg per patient in the tamsulosin group and 675 mg per patient in the control group ( P < 0.001 ) . CONCLUSIONS The results of our study have demonstrated that tamsulosin therapy , as an adjunctive medical therapy after ESWL , is more effective than lithotripsy alone for the treatment of patients with large renal stones and is equally safe . In addition , our results also indicated that adjunctive treatment with tamsulosin could decrease the use of analgesic drugs after ESWL Extracorporeal shock wave lithotripsy ( ESWL ) is currently considered one of the main treatments for ureteral stones . Some studies have reported the effectiveness of pharmacologic therapies ( calcium antagonists or alpha-blockers ) in facilitating ureteral stone expulsion after ESWL . We prospect ively evaluated the efficacy , after ESWL , of nifedipine on upper-middle ureteral stones , and tamsulosin on lower ureteral stones , both associated to ketoprofene as anti-edema agent . From January 2003 to March 2005 we prospect ively evaluated 113 patients affected by radiopaque or radiolucent ureteral stones . Average stone size was 10.16 ± 2.00 mm ( range 6–14 mm ) . Thirty-seven stones were located in the upper ureter , 27 in the middle ureter , and 49 in the lower ureter . All patients received a single session of ESWL ( mean number of shock waves : 3,500 ) by means of a Dornier Lithotripter S ( mean energy power for each treatment : 84 % ) . Both ultrasound and X-ray were used for stone scanning . After treatment , 63 of 113 patients were su bmi tted to medical therapy to aid stone expulsion : nifedipine 30 mg/day for 14 days administered to 35 patients with upper-middle ureteral stones ( group A1 ) and tamsulosin 0.4 mg/day for 14 days administered to 28 patients with stones located in the distal ureter ( group A2 ) . The remaining 50 patients were used as a control group ( 29 upper – middle ureteral stones — B1— and 21 lower ureteral stones — B2— ) , receiving only pain-relieving therapy . No significant difference in stone size between the groups defined was observed . Stone clearance was assessed 1 and 2 months after ESWL by means of KUB , ultrasound scan and /or excretory urography . A stone-free condition was defined as complete stone clearance or the presence of residual fragments smaller than 3 mm in diameter . The stone-free rates in the expulsive medical therapy group were 85.7 and 82.1 % for the nifedipine ( A1 ) and tamsulosin ( A2 ) groups respectively ; stone-free rates in the control groups were 51.7 and 57.1 % ( B1 and B2 , respectively ) . Five patients ( 14.3 % ) in group A1 , 5 ( 17.8 % ) in group A2 , 14 ( 48.3 % ) in group B1 and 9 ( 42.8 % ) in group B2 were not stone-free after a single ESWL session and required ESWL re-treatment or an endoscopic treatment . Medical therapy following ESWL to facilitate ureteral stone expulsion results in increased 1- and 2-month stone-free rates and in a lower percentage of those needing re-treatment . The efficacy of nifedipine for the upper-mid ureteral tract associated with ketoprofene makes expulsive medical therapy suitable for improving overall outcomes of ESWL treatment for ureteral stones Drugs are increasingly being used to promote stone passage in renal colic . Diclofenac , nifedipine and tamsulosin cause ureteric smooth muscle relaxation in vitro ; however , in clinical trials nifedipine and tamsulosin promote stone passage whereas diclofenac has no apparent benefit . We adapted a ureteric pressure transducer catheter in an attempt to compare the human ureteric response to these drugs in vivo . The catheter was inserted into the contralateral ureter following ureteroscopy for stone disease . Contraction frequency , pressure and velocity measurements were recorded at 24 h. Each patient was r and omly allocated to receive oral diclofenac , nifedipine or tamsulosin . Measurements were taken following drug administration . Eighteen patients ( mean age 50 years ) were recruited . Two patients were excluded intraoperatively and three required early removal of the catheter . Prior to drug administration , the mean number of contractions recorded was 0–4.1/min and the peak contraction pressure ranged from 11 to 35 mmHg . Conduction velocity ranged from 1.5 to 2.6 cm/s . Ureteric peristalsis persisted in all patients despite these drugs . Diclofenac and nifedipine produced inconsistent ureteric pressure responses but had little effect on contraction frequency . Tamsulosin significantly reduced ureteric pressure but had no effect on contraction frequency . There are many limitations associated with the use of ureteric catheters , however , they may provide some useful information when used to record the response to an intervention in the same patient . These preliminary results suggest a reduction in pressure generation may be the essential factor in the promotion of stone passage . More work is required but these drugs may work by preventing the increased , uncoordinated muscular activity seen in renal colic whilst maintaining peristalsis , thereby promoting stone passage PURPOSE To evaluate the efficacy of the addition of tamsulosin to our st and ard expulsive pharmacologic therapy for the treatment of distal-ureteral stones . PATIENTS AND METHODS A series of 96 patients referred to our department for the management of symptomatic distal-ureteral calculi were r and omly divided into group 1 ( N = 46 ) who received diclofenac ( 100 mg/daily ) plus aescin ( 80 mg/daily ) and group 2 ( N = 50 ) who received the same therapy plus tamsulosin ( 0.4 mg/daily ) for a maximum of 2 weeks . There were no differences between the groups with respect Output:	Pooled analyses suggest that MET with alpha-blockers or calcium channel blockers augments stone expulsion rates , reduces the time to stone expulsion , and lowers analgesia requirements for ureteral stones with and without ESWL for stones < or = 10 mm . There is some evidence that a combination of alpha-blockers and corticosteroids might be more effective than treatment with alpha-blockers alone . Renal stones after ESWL also seem to profit from MET .
MS21962	*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 Oocyte cryopreservation is an important method used in a number of human fertility circumstances . Here , we compared the survival , in vitro maturation , fertilization , and early embryonic development rates of frozen-thawed human immature oocytes using two different cryopreservation methods . Methods A total of 454 failed-matured oocytes [ germinal vesicle ( GV ) and metaphase I ( MI ) stages ] were collected from 135 patients ( mean age 33.84 + /- 5.0 y ) who underwent intracytoplasmic sperm injection ( ICSI ) cycles between February 2009 and December 2009 and r and omly divided into a slow freezing group [ 1.5 mol/L-1 , 2-propanediol ( PROH ) + 0.2 mol/l sucrose ] and vitrification group [ 20 % PROH + 20 % ethylene glycol ( EG ) + 0.5 mol/l sucrose ] . Results The vitrification protocol yielded a better survival rate than the slow freezing protocol at each maturation stage assessed . Regardless of the maturation stage ( GV + MI ) , the slow freezing protocol had a significantly lower survival rate than the vitrification protocol ( p < 0.001 ) . In addition , a significant difference was found in the survival rates between GV and MI oocytes regardless of the protocol used ( 90.1 vs. 64.7 % , respectively ; p < 0.01 ) . We also found that the maturation rates of GV and MI oocytes from the slow freezing and vitrification groups were 16.7 vs. 24.4 % and 50.8 vs. 55.4 % , respectively . Regardless of the protocol used , the GV oocytes had significantly lower viability than MI oocytes after 36 h of in vitro maturation ( 21.2 vs. 54.0 % , respectively ; p < 0.01 ) . In addition , the GV and MI oocytes from the slow freezing group had a markedly lower maturation rate than those from the vitrification group ( 33.6 vs. 43.1 % , respectively ) , but no statistical difference was found between the two groups ( P > 0.05 ) . For the GV-matured oocytes , no fertilized eggs were obtained in the slow-freezing group , while a 19.0 % ( 4/21 ) fertilization rate was observed in the vitrification group . For the MI-matured oocytes , fertilization rates for the slow freezing and vitrified groups were 36 % and 61.1 % , respectively , but no significant difference was found between the two groups ( PIn the Methods section in the MS , all procedures were compliant with ethical guidelines , i.e. approved by the Ethical Committee of our university and Informed Consent signed by each patient . > 0.05 ) . In the GV vitrification group , no embryo formed ; however , in the MI slow freezing group , 12 oocytes were fertilized , but only two achieved cleavage and were subsequently blocked at the 2-cell stage . In the MI vitrification group , a total of 22 embryos were obtained , five of which developed to the blastocyst stage . Conclusions Vitrification is superior to the slow freezing method in terms of the survival and developmental rates for the cryopreservation of human failed-matured oocytes . In addition , GV oocytes appeared to be more resistant than MI oocytes to the low temperature and cryoprotectant used during cryopreservation BACKGROUND An efficient oocyte cryopreservation method is m and atory to establish a successful egg-banking programme . Although there are increasing reports showing good clinical outcomes after oocyte cryopreservation , there is still a lack of large controlled studies evaluating the effectiveness of oocyte cryo-banking . In this study , we aim ed to compare the outcome of vitrified-banked oocytes with the gold st and ard procedure of employing fresh oocytes . METHODS A r and omized , prospect i ve , triple-blind , single-centre , parallel-group controlled- clinical trial ( NCT00785993 ) , including 600 recipients ( alpha = 0.05 and power of 80 % for sample -size calculation ) selected among 1032 eligible patients from November 2008 to September 2009 , was design ed to compare the outcome of vitrified-banked oocytes with the gold st and ard procedure of employing fresh oocytes . The study was design ed to establish the superiority of the ongoing pregnancy rate ( OPR ) of fresh oocytes over that of vitrified oocytes , by performing a likelihood ratio test in a logistic regression analysis expressed as odds ratio ( OR ) with 95 % confidence interval ( CI ) . A limit of 0.66 for OR of vitrified versus fresh groups was defined to set up a possible conversion from superiority to non-inferiority . R and omization was performed 1:1 based on a computer r and omization list in vitrification ( n = 300 ) or fresh groups ( n = 300 ) . The primary end-point was the OPR per r and omized patient i.e. intention-to-treat population ( ITT ) . Secondary end-points were clinical pregnancy ( CPR ) , implantation ( IR ) and fertilization rates , respectively . Additionally , embryo developmental characteristics were recorded . RESULTS There were no differences in donor ovarian stimulation parameters , demographic baseline characteristics for donors and recipients , ovum donation indications or male factor distribution between groups ( NS ) . The OPR per ITT was 43.7 and 41.7 % in the vitrification and fresh groups , respectively . The OR of OPR was 0.921 in favour of the vitrification group . Nevertheless , the 95 % CI was 0.667 - 1.274 , thus the superiority of fresh group with respect to OPR was not proven ( P = 0.744 ) . Non-inferiority of the vitrified group compared with the fresh group was shown with a margin of 0.667 , which was above the pre-established non-inferiority limit of 0.66 . CPR per cycle ( 50.2 versus 49.8 % ; P = 0.933 ) or per embryo-transfer ( 55.4 versus 55.6 % ; P = 0.974 ) , and IR ( 39.9 versus 40.9 % ; P = 0.745 ) were similar for patients receiving either vitrified or fresh oocytes . The proportion of top- quality embryos obtained either by inseminated oocyte ( 30.8 versus 30.8 % for Day-2 ; and 36.1 versus 37.7 % for Day-3 , respectively ) or by cleaved embryos ( 43.6 versus 43.8 % for Day-2 and 58.4 versus 60.7 % for Day-3 , respectively ) was similar between groups ( NS ) . CONCLUSIONS This controlled-r and omized , clinical trial confirmed the effectiveness of oocyte cryo-storage in an ovum donation programme , failing to demonstrate the superiority of using fresh oocytes with respect to the use of vitrified egg-banked ones in terms of OPR . Instead , the non-inferiority of vitrified oocytes was confirmed . These findings involve highly relevant issues that may open a new range of possibilities in ART STUDY QUESTION How does vitrification affect oocyte viability ? SUMMARY ANSWER Vitrification does not affect oocyte viability in oocyte donation cycles . WHAT IS KNOWN ALREADY Oocyte vitrification is performed routinely and successfully in IVF and oocyte donation programs . STUDY DESIGN , SIZE , DURATION This is a prospect i ve study performed between June 2009 and February 2012 to compare ongoing pregnancy rates and other indices of viability between fresh and vitrified oocytes . A total of 99 donations with more than 16 oocytes ( MII ) in which oocytes were allocated both to a synchronous recipient ( fresh oocytes ) and to an asynchronous recipient ( vitrified oocytes ) were included . PARTICIPANTS / MATERIAL S , SETTING , METHODS The participants were consenting couples ( donors and recipients ) from the oocyte donation program . On the day of retrieval , the oocytes allocated to the synchronous recipient were inseminated and those allocated for banking were denuded of cumulus and vitrified . Vitrified oocytes were microinjected with spermatozoa 2 h after warming . Embryo transfer was performed on Day 2 of development in both groups , and the remaining embryos were cryopreserved on Day 3 . Clinical pregnancy was defined by a positive fetal heartbeat at 6 weeks . MAIN RESULTS AND ROLE OF CHANCE A total of 989 oocytes were warmed and 85.6 % survived . No significant differences were observed between fresh and vitrified oocytes : fertilization rate ( 80.7 versus 78.2 % ) , ongoing embryo rate ( 71.0 versus 68.2 % ) or good- quality embryo rate ( 54.1 versus 49.8 % ) . The mean number of embryos transferred was similar in both groups ( 1.82 ± 0.44 versus 1.90 ± 0.34 ) . The implantation rate ( 33.3 versus 34.0 % ) and the multiple pregnancy rate ( 27.7 versus 20.8 ) were also similar between both groups ( P > 0.05 ) . The live birth rate per cycle was 38.4 % in the recipients of fresh oocytes and 43.4 % in the recipients of vitrified oocytes ( P > 0.05 ) . Eighty five frozen embryo transfers were also evaluated . Comparing embryos from fresh and vitrified oocytes there were no significant differences in the embryo survival rate ( 70.1 versus 65.8 % ) , clinical pregnancy rate ( 40.8 versus 33.3 % ) or implantation rate ( 21.8 versus 26.8 % ) . LIMITATIONS , REASONS FOR CAUTION The oocytes were donated by healthy , young women ( ≤35 years ) and these results can not be extrapolated to other population s. WIDER IMPLICATION S OF THE FINDINGS Outcomes obtained with vitrified oocytes are as good as with fresh oocytes and the use of vitrification can be extended to new applications , e.g. accumulation of oocytes from successive stimulations for preimplantation genetic diagnosis , for patients at risk of ovarian hyperstimulation syndrome or in patients needing to preserve their fertility . STUDY FUNDING /COMPETING INTEREST(S ) This work was done under the auspices of the Càtedra d'Investigació en Obstetrícia i Ginecologia of the Universitat Autònoma de Barcelona Accumulation of oocytes from several ovarian stimulation cycles is currently possible using novel vitrification technologies . This strategy could increase the inseminated cohort , creating a similar situation to normoresponders . This study included 242 low-responder ( LR ) patients ( 594 cycles ) whose mature oocytes were accumulated by vitrification and inseminated simultaneously ( LR-Accu-Vit ) and 482 patients ( 588 cycles ) undergoing IVF/embryo transfer with fresh oocytes in each stimulation cycle ( LR-fresh ) . Drop-out rate in the LR-fresh group was > 75 % . The embryo-transfer cancellation per patient was significantly lower in the LR-Accu-Vit group ( 9.1 % ) than the LR-fresh group ( 34.0 % ) . Live-birth rate (LBR)/patient was higher in the LR-Accu-Vit group ( 30.2 % ) than the LR-fresh group ( 22.4 % ) . Cumulative LBR/patient was statistically higher in the LR-Accu-Vit group ( 36.4 % ) than the LR-fresh group ( 23.7 % ) and a similar outcome was observed among patients aged ⩾40years ( LR-Accu-Vit 15.8 % versus LR-fresh 7.1 % ) . The LR-Accu-Vit group had more cycles with embryo cryopreservation ( LR-Accu-Vit 28.9 % versus LR-fresh 8.7 % ) . Accumulation of oocytes by vitrification and simultaneous insemination represents a successful alternative for LR patients , yielding comparable success rates to those in normoresponders and avoiding adverse effects of a low response . The accumulation of oocytes from several ovarian stimulation cycles is currently possible with the aid of novel vitrification technologies . This strategy could be useful for low-responder patients , contributing to increase the inseminated cohort and creating a similar situation as in normal responders . According to the results presented herein ( higher live-birth rate per patient treated ) , this strategy represents a successful alternative for low-responder patients , yielding comparable success rates to those in normal responders and avoiding the adverse effects of a low response OBJECTIVE To compare the survival , fertilization , early embryonic development , and meiotic spindle assembly and chromosome alignment in frozen-thawed human oocytes after slow-freezing and vitrification . DESIGN A r and omized study . SETTING A university-affiliated assisted reproductive center . PATIENT(S ) Donated extra eggs from women undergoing assisted reproduction treatment . INTERVENTION(S ) A total of 605 mature oocytes were divided into a slow-freezing group and a vitrification group for cryopreservation . MAIN OUTCOME ME Output:	Oocyte vitrification compared to slow freezing probably increases clinical pregnancy rates in women undergoing assisted reproduction .
MS21963	*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 objective was to compare targeting increased eating of healthy foods vs. reducing intake of high energy-dense foods within the context of a family-based behavioral weight control program . METHODS AND PROCEDURES Forty-one 8 - 12 year-old children > 85th BMI percentile were r and omly assigned to a 24-month family-based behavioral treatment that targeted increasing fruits and vegetables and low-fat dairy vs. reducing intake of high energy-dense foods . RESULTS Children in the increase healthy food group showed greater reduction in z BMI compared to children in the reduce high energy-dense food group at 12- ( -0.30 z BMI units vs. -0.15 z BMI units , P = 0.01 ) and 24- ( -0.36 z BMI units vs -0.13 z BMI units , P = 0.04 ) month follow-up . Parents in the increase healthy food group showed greater reductions in concern about child weight ( P = 0.007 ) , and these changes were associated with child z BMI change ( P = 0.008 ) . Children in the reduce high energy-dense group showed larger sustained reductions in high energy-dense foods ( P < 0.05 ) . Baseline levels of high energy-dense foods ( P < 0.05 ) , parent food restraint ( P = 0.01 ) , parent concern over parent weight ( P = 0.01 ) and parent acceptance of the child ( P < 0.05 ) moderated child z BMI change , with greater sustained reductions in z BMI for children in the increase healthy food group for each measure . Parent z BMI change followed the same pattern as child changes , and parent and child z BMI changes were correlated ( P < 0.001 ) . DISCUSSION Focusing on healthy food choices within an energy restricted diet may be useful in family-based weight control programs Background . Prevention of cardiovascular disease through diet and lifestyle change is strongly advocated in adults and is initiated preferably during childhood . The Dietary Intervention Study in Children ( DISC ) was a multicenter , collaborative , r and omized trial in 663 preadolescent children ( 363 boys and 301 girls ) with elevated low-density lipoprotein cholesterol , design ed to test the efficacy and safety of a dietary intervention to lower saturated-fat and cholesterol intake while also advocating a healthy eating pattern . DISC results have been published extensively . This ancillary study reports new data regarding changes in eating patterns among this cohort . Objective . We set out to compare children 's self-selected eating patterns and approaches to achieving adherence to the DISC fat-reduced diet intervention with children in the usual-care group . Methods . An ancillary study was conducted to develop a detailed food-grouping system and report new analyses on dietary adherence to the recommended eating pattern . Every food in the nutrient data base was ranked by its saturated-fat and cholesterol content and classified within its relevant food group as a “ go ” ( less atherogenic ) or “ whoa ” ( more atherogenic ) food . Results . At baseline , go foods contributed ∼57 % of total energy intake and 12.4 % to 13.1 % total fat energy intake in both groups . At 3 years , go foods contributed 67.4 % and 13.7 % of total and fat energy intake , respectively , in the intervention group versus 56.8 % and 12.8 % in the usual-care group . Differences between the 2 treatment groups were significant for changes in consumption of dairy foods , desserts , and fats/oils , with the intervention group reporting a 0.2- to 0.3-serving-per-day greater increase in go foods than the usual-care group . The intervention group also reported a 0.2- to 0.8-serving-per-day greater decrease in whoa foods than the usual-care group for breads/grains , dairy , fats/oils , meat/fish/poultry , snacks , and vegetables . Overall , snack foods , desserts , and pizza contributed approximately one third of total daily energy intake in both groups at 3 years . Conclusions . Children in the intervention group reported consuming more servings per day of go grains , dairy , meats , and vegetable foods compared with children in the usual-care group , but intake of fruits and vegetables was low in both groups . Discovering that snacks , desserts , and pizza actively contribute so heavily to the diets of this age group , even among children who were part of this intervention , offers valuable insights regarding the need for more aggressive , innovative , and realistic approaches for additional dietary counseling BACKGROUND During the nutrition transition in Chile , dietary changes were marked by increased consumption of high-energy , nutrient-poor products , including sugar-sweetened beverages ( SSBs ) . Obesity is now the primary nutritional problem in posttransitional Chile . OBJECTIVE We conducted a r and omized controlled trial to examine the effects on body composition of delivering milk beverages to the homes of overweight and obese children to displace SSBs . DESIGN We r and omly assigned 98 children aged 8 - 10 y who regularly consumed SSBs to intervention and control groups . During a 16-wk intervention , children were instructed to drink 3 servings/d ( approximately 200 g per serving ) of the milk delivered to their homes and to not consume SSBs . Body composition was measured by dual-energy X-ray absorptiometry . Data were analyzed by multiple regression analysis according to the intention-to-treat principle . RESULTS For the intervention group , milk consumption increased by a mean ( + /- SEM ) of 452.5 + /- 37.7 g/d ( P < 0.0001 ) , and consumption of SSBs decreased by -711.0 + /- 33.7 g/d ( P < 0.0001 ) . For the control group , milk consumption did not change , and consumption of SSBs increased by 71.9 + /- 33.6 g/d ( P = 0.04 ) . Changes in percentage body fat , the primary endpoint , did not differ between groups . Nevertheless , the mean ( + /- SE ) accretion of lean body mass was greater ( P = 0.04 ) in the intervention ( 0.92 + /- 0.10 kg ) than in the control ( 0.62 + /- 0.11 kg ) group . The increase in height was also greater ( P = 0.01 ) in the intervention group ( 2.50 + /- 0.21 cm ) than in the control group ( 1.77 + /- 0.20 cm ) for boys but not for girls . CONCLUSION Replacing habitual consumption of SSBs with milk may have beneficial effects on lean body mass and growth in children , despite no changes in percentage body fat . This trial was registered at clinical trials.gov as NCT00149695 Background A two-year , community-based , group-r and omized trial to promote bone mass gains among 9–11 year-old girls through increased intake of calcium-rich foods and weight-bearing physical activity was evaluated . Methods Following baseline data collection , 30 5th- grade Girl Scout troops were r and omized to a two-year behavioral intervention program or to a no-treatment control group . Evaluations were conducted at baseline , one year , and two years . Measures included bone mineral content , density , and area ( measured by DXA ) , dietary calcium intake ( 24-hour recall ) , and weight-bearing physical activity ( physical activity checklist interview ) . Mixed-model regression was used to evaluate treatment-related changes in bone mineral content ( g ) for the total body , lumbar spine ( L1-L4 ) , proximal femur , one-third distal radius , and femoral neck . Changes in eating and physical activity behavioral outcomes were examined . Results Although the intervention was implemented with high fidelity , no significant intervention effects were observed for total bone mineral content or any specific bone sites . Significant intervention effects were observed for increases in dietary calcium . No significant intervention effects were observed for increases in weight-bearing physical activity . Conclusion Future research needs to identify the optimal dosage of weight-bearing physical activity and calcium-rich dietary behavior change required to maximize bone mass gains in pre-adolescent and adolescent girls The purpose was to study if serving milk or water with the lunch at preschool influenced 6- to 7-year-old children 's preferences for and later choice between milk and water at lunch in elementary school later . Children ( n = 147 ) at 12 daycare centres were usually served water at lunch but , for 3 months , six r and omly chosen centres served milk at lunch ( Intervention group ) and six matched centres continued serving water ( Control group ) . The groups did not differ with respect to preferences for seven types of beverages ( including water and four varieties of milk ) either before or after the intervention . Four and 12 months later , their choice of lunch drink ( milk or water ) at school was studied for two 5-week periods . At the 4-month assessment , the children in the Intervention group chose milk at lunch significantly more often than did those in the Control group ( 92 % vs. 81 % of the days ) , while there were no significant differences at 12 months ( 85 % vs. 81 % ) . Since there were no demonstrable effects on preferences , one interpretation of the results is that children tend to associate the type of drink regularly served at a meal with that specific meal Objectives : To examine if and how ready-to-eat cereals ( RTEC ) contribute to the quality of the diet of children , adolescents and young adults in a Mediterranean setting . Methods : A r and om sample of 3534 subjects aged 2 to 24 years in Spain was studied . Food and nutrient intakes were determined by a 24 hour recall . RTEC consumption was assessed by a quantitative food frequency question naire . Additional questions on socioeconomic level and nutritional knowledge were administered . Cereal consumption was classified into non-consumers and daily intakes between 1 and 20 g , 21 and 40 g , and more than 40 g . After excluding the underreporters the final sample consisted of 2852 individuals . Results : About half of the population ( 49.8 % ) reported eating RTEC . Macronutrient profile improved with increasing cereal consumption . Intakes of thiamine , riboflavin and vitamin B6 increased significantly with increasing consumption of RTEC in all age-sex groups , whereas niacin and folate intake improved in almost all groups and calcium , iron and vitamin D in at least half of the groups . Except for magnesium , vitamin B12 and vitamin E in males , consumption of RTEC was significantly associated with increased coverage of the daily nutrient requirements for all micronutrients studied . Higher levels of RTEC consumption was associated with a greater consumption of dairy products , and related to better breakfast quality . Conclusions : Level of RTEC consumption is associated with a better nutritional profile in the diets of Spanish children , adolescents and young adults and a lower risk for inadequate micronutrient intakes . RTEC consumers have better quality breakfasts , in terms of both food choices as well as energy and nutrient content BACKGROUND This paper describes the impact of the Eat Smart School Nutrition Program , the food service component of the Child and Adolescent Trial for Cardiovascular Health ( CATCH ) , on the percentage of calories from total fat and saturated fat and the sodium content of school breakfasts . METHODS Fifty-nine of the 96 CATCH schools offered breakfast . We collected 5 consecutive days of school breakfast menu , recipe , and vendor product information at three periods to assess the nutrient content of the school menus as offered . RESULTS At baseline ( Fall 1991 ) , intervention school breakfasts provided 28 % of calories from total fat and control schools 30 % . Decreases occurred over time in both groups , but no significant differences were attributable to the intervention ( adjusted mean difference = -0.4 ; P = 0.77 ) . Saturated fat exceeded the Eat Smart goal at baseline in all schools and by follow-up ( Spring 1994 ) , the reduction in mean percentage of calories from saturated fat was greater in intervention than in control schools ( adjusted mean difference = -1.6 % ; P = 0.052 ) . Sodium goals were not achieved . Mean calorie levels were maintained at or above Eat Smart goals throughout the study in both groups . Differences over time in other dietary variables ( percentage of calories from protein and carbohydrate and mean levels of protein , carbohydrate , calcium , iron , vitamin A value , vitamin C , total sugars , and dietary fiber ) were not statistically significant between groups . No significant reductions in student participation in the School Breakfast Program ( SBP ) occurred . CONCLUSIONS The Eat Smart food service intervention improved school breakfast composition , but not significantly more so than in control schools . Fat and saturated fat in school breakfasts were lowered while maintaining calories , other essential nutrient levels , and student participation in the SBP . Secular trends and also the possibility that control schools were affected by the Eat Smart intervention may account for these findings BACKGROUND Poor nutrition and inactivity are widespread and contribute to the epidemic problem of childhood obesity . This study examined the effectiveness of a school-based pilot program to improve nutrition and activity in elementary ( ES ) and high school ( HS ) students . METHODS The Improving Meals and Physical Activity in Children and Teens ( IMPACT ) school-based curriculum used a train-the-trainer model to improve activity and nutrition . Nine students were recruited from one rural North Carolina high school and trained in the IMPACT curriculum Output:	Effective interventions tended to be higher in intensity , provide dairy foods and were delivered across a variety of setting s to a range of primary targets . The number of behaviour change techniques used did not differentiate effective and ineffective interventions , but the use of taste exposure and prompting practice appeared to be important for effective intervention . Interventions that target an increase in children 's dairy food or Ca intake could potentially increase children 's dairy food intake by about one serving daily . The review has identified some promising strategies likely to be part of effective interventions for improving dairy and Ca intakes in countries where children 's intake is insufficient
MS21964	*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 : Ultrasound-guided transversus abdominis plane ( TAP ) block has recently come up as a modality to take care of postoperative pain . It can somewhat avoid the use of intravenous opioid analgesics and hence to avoid its complications . We have performed a prospect i ve , double-blinded , r and omized study to assess the analgesic effect of adding dexmedetomidine to local ropivacaine on TAP block for patients undergoing lower abdominal surgeries . Aim : The aim is to assess whether addition of dexmedetomidine to ropivacaine may bring some improvements to the analgesic efficacy of TAP blocks in patients undergoing lower abdominal surgeries . Material s and Methods : The study was conducted on forty patients undergoing lower abdominal surgeries under general anesthesia . The patients were divided into two groups : one receiving plain ropivacaine ( Group 1 ) and other receiving ropivacaine with dexmedetomidine ( Group 2 ) during TAP block . The patients in the two groups were compared for age , sex , body mass index , incidence of postoperative nausea , and vomiting and pain as measured on visual analog scale ( VAS ) . Results : There was significantly lower pain score on VAS at 1 , 3 , 6 , 12 , and 18 h in Group 2 than in Group 1 . Conclusion : The addition of dexmedetomidine to ropivacaine during TAP block improves analgesic effect of TAP block and prolongs the duration of analgesia as well BACKGROUND : Superior early pain control has been suggested with transversus abdominis plane blocks , but evidence -based recommendations for transversus abdominis plane blocks and their effects on patient outcomes are lacking . OBJECTIVE : The aim of this study was to determine whether transversus abdominis plane blocks improve early postoperative outcomes in patients undergoing laparoscopic colorectal resection already on an optimized enhanced recovery pathway . DESIGN : This study is based on a prospect i ve , r and omized , double-blind controlled trial . SETTING S : The trial was conducted at a tertiary referral center . PATIENTS : Patients undergoing elective laparoscopic colorectal resection were selected . INTERVENTIONS ( S ) : Patients were r and omly assigned to receive either a transversus abdominis plane block or a placebo placed intraoperatively under laparoscopic guidance . All followed a st and ardized enhanced recovery pathway . Patient demographics , perioperative procedures , and postoperative outcomes were collected . MAIN OUTCOME MEASURES : Postoperative pain and nausea/vomiting scores in the postanesthesia care unit and department , opioid use , length of stay , and 30-day readmission rates were measured . RESULTS : The trial r and omly assigned 41 patients to the transversus abdominis plane block group and 38 patients to the control group . Demographic , clinical , and procedural data were not significantly different . In the postanesthesia care unit , the transversus abdominis plane block group had significantly lower pain scores ( p < 0.01 ) and used fewer opioids ( p < 0.01 ) than the control group ; postoperative nausea/vomiting scores were comparable ( p = 0.99 ) . The transversus abdominis plane group had significantly lower pain scores on postoperative day 1 ( p = 0.04 ) and throughout the study period ( p < 0.01 ) . There was no significant difference between groups in postoperative opioid use ( p = 0.65 ) or nausea/vomiting ( p = 0.79 ) . The length of stay ( median , 2 days experimental , 3 days control ; p = 0.50 ) and readmission rate ( 7 % experimental , 5 % control , p = 0.99 ) was similar across cohorts . LIMITATIONS : This study was conducted a single center . CONCLUSIONS : Transversus abdominis plane blocks improved immediate short-term opioid use and pain outcomes . Pain improvement was durable throughout the hospital stay . However , the blocks did not translate into less overall narcotic use , shorter length of stay , or lower readmission rates Background The transversus abdominis plane block is recently described peripheral block to providing analgesia to the anterior abdominal wall . The goal of this study is to evaluate the analgesic efficacy of the ultrasound-guided transversus abdominis plane block ( US-TAP block ) in patients undergoing gynecologic surgery via a transverse lower abdominal skin incision . Methods Thirty-two patients undergoing gynecologic surgery were r and omized to undergo st and ard care such as PCA , or to receive additional US-TAP block with st and ard care . After general anesthesia induction , a bilateral US-TAP block was performed using 0.375 % ropivacaine 20 ml on each side . Postoperative dem and of rescue analgesics in PACU and ward were recorded . Each patient was assessed postoperatively by a blinded investigator in the postanesthesia care unit ( PACU ) and at 2 , 6 , 10 , 24 , 48 hr postoperatively to investigate pain , drowsiness , nausea and itch . Results The US-TAP block reduced pain intensity compared to st and ard care in the PACU ( 5.2 ± 3.1 vs 8.4 ± 1.3 ) and at 2 , 24 postoperative hours ( 3.0 ± 2.4 vs 5.2 ± 2.4 , 0.9 ± 1.5 vs 2.2 ± 1.9 ) . Fentanyl requirements in PACU was reduced ( 20.3 ± 20.9 vs 62.5 ± 35.4 µg , P < 0.05 ) . In ward , pethidine requirements was reduced ( 21.9 ± 28.7 vs 56.3 ± 34.8 mg , P < 0.05 ) . Conclusions The US-TAP block with st and ard care provide more effective analgesia after gynecologic surgery via a transverse lower abdominal skin incision Background Although enhanced recovery pathways ( ERPs ) may permit early recovery and discharge after laparoscopic colorectal surgery ( LC ) , most publications report that the mean hospital stay is 4 and 6 days . This study evaluates the addition of a transversus abdominis plane ( TAP ) block to the st and ard ERP . Methods In this study , 35 consecutive elective patients received a TAP block at the end of LC . The patients were matched by operation , diagnosis , age , gender , and body mass index ( BMI ) with 35 recent cases and followed in a prospect i ve institutional review board (IRB)-approved data base . All the patients were managed with a st and ardized ERP . The surgeon placed TAP blocks under laparoscopic guidance that infiltrated 15 ml of 0.5 % Marcaine on both sides of the abdomen . Results The cases included 8 low pelvic anastomoses , 4 proctectomies with or without an ileal pouch anal anastomosis , 5 sigmoid/left colectomies , 13 ileocolic/right colectomies , 1 total colectomy , and 5 others . The mean age was 59 years for the TAP group and 64.1 years for the control group ( p = 0.21 ) . The mean hospital stay was 2 days for the TAP patients and 3 days for the control patients ( p = 0.000013 ) . Of the 35 TAP patients , 13 went home on postoperative day ( POD ) 1 ( 37 % ) , 12 on POD 2 ( 34 % ) , 8 on POD 3 ( 23 % ) , and the remainder on POD 4 . Of the 35 control patients , 1 went home on POD 1 ( 3 % ) , 10 on POD 2 ( 29 % ) , 10 on POD 3 ( 29 % ) , 11 on POD 4 ( 31 % ) , and the remainder on POD 5 to 8 . The TAP patients required fewer narcotics postoperatively than the control patients ( respective mean morphine equivalents , 31.08 vs. 85.41 ; p = 0.01 ) . Discussion A bilateral TAP block significantly improved the results of an established ERP for patients undergoing LC . Surgeon-administered TAP blocks may be an economical and efficient method for improving the results of LC INTRODUCTION Opioid sparing in postoperative pain management appears key in colorectal enhanced recovery . Transversus abdominis plane ( TAP ) blocks offer such an effect . This study aim ed to quantify this effect on pain , opioid use and recovery of bowel function after laparoscopic high anterior resection . METHODS This was a retrospective analysis of prospect i ve data on 68 patients . Patients received an epidural ( n=24 ) , intravenous morphine patient controlled analgesia ( PCA , n=22 ) or TAP blocks plus PCA ( n=22 ) determined by anaesthetist preference . Outcome measures were numerical pain scores ( 0 - 3 ) , cumulative intravenous morphine dose and time to recovery of bowel function ( passage of flatus or stool ) . RESULTS There were no differences in patient characteristics , complications or extraction site . The TAP block group had lower pain scores ( 0.7 vs 1.36 , p<0.001 ) and morphine requirements ( 8 mg vs 15 mg , p=0.01 ) than the group receiving PCA alone at 12 hours and 24 hours . Earlier passage of flatus ( 2.0 vs 2.7 vs 3.4 days , p=0.002 ) , stool ( 3.1 vs 4.1 vs 5.5 days , p=0.04 ) and earlier discharge ( 4 vs 5 vs 6 days , p=0.02 ) were also seen . CONCLUSIONS Use of TAP blocks was found to reduce pain and morphine use compared with PCA , expedite recovery of bowel function compared with PCA and epidural , and expedite hospital discharge compared with epidural Background The increasing use of laparoscopic techniques for colorectal resections means that the issue of postoperative analgesia needs to be reassessed . This nonr and omized comparative study aim ed to assess the efficacy of the transversus abdominis plane ( TAP ) block in laparoscopic colorectal resections . Methods Prospect ively collected data from consecutive patients undergoing laparoscopic colorectal resections were used . Analgesia usage and outcome data for patients who had a TAP block and a postoperative morphine patient-controlled analgesia pump ( PCA ) were compared with those for patients who had a PCA alone . Results Data for 74 patients were used in the final analysis ( 40 TAP/PCA and 34 PCA alone ) . There was a significant reduction in overall intravenous opiate use in the TAP/PCA group ( 31.3 vs. 51.8 mg ; P = 0.03 ) . The TAP/PCA group showed a slight trend toward a shorter hospital stay ( 3 vs. 4 days ; P = 0.17 ) but no difference in postoperative complications or any other outcome measure . There was no procedure-related morbidity relating to the use of TAP blocks . Conclusions It appears that TAP blocks reduce postoperative analgesia use of patients undergoing laparoscopic colorectal resections within an enhanced recovery program , and this may have an impact on their postoperative hospital length of stay Background Although h and -assisted laparoscopic surgery ( HALS ) offers patients smaller surgical incisions , they still experience pain . Currently , there is no consensus on the optimal analgesic package for patients undergoing HALS . The aim of this prospect i ve , r and omized , double-blinded , placebo-controlled clinical trial was to evaluate the effect of transversus abdominis plane ( TAP ) block on postoperative pain control ( pain score and analgesic use ) and other outcomes in colon cancer patients undergoing h and -assisted laparoscopic left hemicolectomy . Methods Sixty-four patients with colon cancer scheduled for an elective colon resection were enrolled in this study . Patients were r and omized into two groups to receive either TAP block using 20 mL of 0.375 % ropivacaine ( TAP block group : 32 patients ) or 20 mL of 0.9 % normal saline infusion ( placebo group : 32 patients ) . Anaesthetic and surgical techniques were st and ardized . Twenty-four-hour postoperative analgesia was maintained by continuous infusion of 0.1–0.9 µg/kg/h fentanyl and intravenous injection of ketorolac . The primary outcome of the study was postoperative pain control ( pain score and analgesic use ) . Pain was assessed using numeric rating scale at 2 , 4 , 8 , 12 , and 24 h after surgery at rest and during movement . Secondary outcomes included the time to resumption of intestinal function and the length of hospital stay . The data of the two groups were compared using Mann – Whitney U test . All statistical tests were two-tailed at a significance level of 0.05 . Results The patients ’ mean age was 60.50 ± 6.77 years , and 68.75 % of patients were males . The mean body mass index was 26.23 ± 4.83 kg/m2 . The TAP block group had lower pain scores after surgery at 2 , 4 , and 12 h at rest ( p < 0.05 ) , at 2 and 4 h during movement ( p < 0.01 ) and used less fentanyl and ketorolac than the placebo group ( p < 0.01 ) . The mean time to resumption of intestinal function Output:	Conclusions The TAP block using a short-acting anesthetic had a significant effect on the postoperative pain outcome in the early ( 0–2 h ) and late ( 24 h ) period at movement . However , it did not have a significant effect on the postoperative pain outcome in the early ( 0–2 h ) and late ( 24 h ) periods at rest after laparoscopic surgery
MS21965	*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: An emerging body of research has shown that computer-assisted cognitive remediation , consisting of training in attention , memory , language and /or problem-solving , produces improvement in neurocognitive function that generalizes to untrained neurocognitive tests and may also impact symptoms and work functioning in patients with schizophrenia . The active ingredient of these interventions , however , remains unknown as control groups in these studies have typically included few , if any , of the elements of these complex behavioral treatments . This study compared the effects of an extended ( 12-month ) , st and ardized , computer-assisted cognitive remediation intervention with those of a computer-skills training control condition that consisted of many of the elements of the experimental intervention , including hours spent on a computer , interaction with a clinician and non-specific cognitive stimulation . Forty-two patients with schizophrenia were r and omly assigned to one of two conditions and were assessed with a comprehensive neuropsychological test battery before and after treatment . Results revealed that cognitive-remediation training produced a significant improvement in working memory , relative to the computers-skills training control condition , but that there was overall improvement in both groups on measures of working memory , reasoning/executive-function , verbal and spatial episodic memory , and processing speed . Taken together , these findings suggest that specific practice in neurocognitive exercises targeted at attention , memory and language , produce improvements in neurocognitive function that are not solely attributable to non-specific stimulation associated with working with a computer , interacting with a clinician or cognitive challenge , but that non-specific stimulation has a salutary effect on neurocognition as well CONTEXT Despite the availability of efficacious treatments , the long-term course of bipolar disorder is often unfavorable . OBJECTIVE To test the effectiveness of a multicomponent intervention program to improve the quality of care and long-term outcomes for persons with bipolar disorder . DESIGN R and omized controlled trial with allocation concealment and blinded outcome assessment . SETTING Mental health clinics of a group-model prepaid health plan . PATIENTS Of 785 patients in treatment for bipolar disorder who were invited to participate , 509 attended an evaluation appointment , 450 were found eligible to participate , and 441 enrolled in the trial . INTERVENTIONS Participants were r and omly assigned to a multicomponent intervention program or to continued care as usual . Three nurse care managers provided a 2-year systematic intervention program , including the following : a structured group psychoeducational program , monthly telephone monitoring of mood symptoms and medication adherence , feedback to treating mental health providers , facilitation of appropriate follow-up care , and as-needed outreach and crisis intervention . MAIN OUTCOME MEASURES In-person blinded research interviews every 3 months assessed mood symptoms using the Longitudinal Interval Follow-up Examination . Health plan administrative records were used to assess the use and cost of mental health services . RESULTS Intent-to-treat analyses demonstrated that the intervention significantly reduced the mean level of mania symptoms ( z = 2.09 , P = .04 ) and the time with significant mania symptoms ( 19.2 vs 24.7 weeks ; F(1 ) = 6.0 , P = .01 ) . There was no significant intervention effect on mean level of depressive symptoms ( z = 0.19 , P = .85 ) or time with significant depressive symptoms ( 47.6 vs 50.7 weeks ; F(1 ) = 0.56 , P = .45 ) . Benefits of the intervention were found only in a subgroup of 343 persons with clinical ly significant mood symptoms at the baseline assessment . The incremental cost ( adjusted ) of the intervention was 1251 dollars ( 95 % confidence interval , 55 - 2446 dollars ) , including approximately 800 dollars for the intervention program services and an approximate 500 dollars increase in the costs of other mental health services . CONCLUSIONS Population -based systematic care programs can significantly reduce the frequency and severity of mania in bipolar disorder , and cost increases are modest considering the clinical gains . The incorporation of more specific cognitive and behavioral content or more effective medication regimens may be necessary to significantly reduce the symptoms of depression BACKGROUND Patient-clinician communication is central to mental healthcare but neglected in research . AIMS To test a new computer-mediated intervention structuring patient-clinician dialogue ( DIALOG ) focusing on patients ' quality of life and needs for care . METHOD In a cluster r and omised controlled trial , 134 keyworkers in six countries were allocated to DIALOG or treatment as usual ; 507 people with schizophrenia or related disorders were included . Every 2 months for 1 year , clinicians asked patients to rate satisfaction with quality of life and treatment , and request additional or different support . Responses were fed back immediately in screen displays , compared with previous ratings and discussed . Primary outcome was subjective quality of life , and secondary outcomes were unmet needs and treatment satisfaction . RESULTS Of 507 patients , 56 were lost to follow-up and 451 were included in intention-to-treat analyses . Patients receiving the DIALOG intervention had better subjective quality of life , fewer unmet needs and higher treatment satisfaction after 12 months . CONCLUSIONS Structuring patient-clinician dialogue to focus on patients ' views positively influenced quality of life , needs for care and treatment satisfaction Nonadherence to medication is a widespread problem in schizophrenia and is associated with poor clinical outcomes and inappropriate management and utilization of re sources . The aim of the current investigation was to assess the impact of telemonitoring of medication adherence on symptomatology and service use in patients with schizophrenia . A total of 108 schizophrenia patients were r and omized into three equal groups according to the approaches used to assess medication adherence ; self-report , pill counting , and telemonitoring . Telementoring was achieved through an innovative new platform called @HOME . This platform offers clinicians early warnings about impeding nonadherence as well as information about the pattern of medication taking . Patient 's adherence was observed over an 8-week period , during which patient 's clinical status and service use were recorded . In comparison to the other two groups , patients using @HOME showed improvement in the Global Clinical Impression Scale and a significant reduction in emergency visits and medical appointments . The @HOME platform was highly acceptable by patients , caregivers , and professionals , and required minimal training for implementation . The results of the study suggest that the use of telemonitoring in psychiatric setting s was both feasible and acceptable and may be associated with significant clinical and service related benefits INTRODUCTION Schizophrenic patients present cognitive dysfunctions which are regarded to be one of endophenotypical markers predisposing to schizophrenia . Currently , schizophrenia can be treated as a neurodegenerative and neurodeveloping disease with genetic background . OBJECTIVE Assessment of the possible positive effect of neuropsychological rehabilitation in schizophrenia , in patients presenting cognitive dysfunctions . An additional aim was to verify the hypothesis that some genetic polymorphisms can be a prognostic factor for success in neuropsychological rehabilitation . MATERIAL AND METHODS 41 participants and 40 control subjects were r and omly selected . Both groups had the diagnosis of paranoid schizophrenia . Cognitive functions were checked with the Wisconsin Card Sorting Test , Trail Making Test , and Stroop Test at the beginning and end of the experiment . In the research group , each patient trained with the rehabilitation programme RehaCom , whereas the control group did not receive such training . Genes COMT rs4680 and BDNF rs6265 were analysed in the genetic part of study . RESULTS RehaCom procedures appear to be useful in the neuropsychological rehabilitation of cognitive dysfunctions in patients diagnosed with schizophrenia . The research group showed a moderate improvement in the training programmes . Analysis of parameters obtained in the neuropsychological tests showed a slight improvement in both groups . At the present time , analysis of the polymorphisms of genes can not be treated as a prognostic factor for the success of neuropsychological rehabilitation because statistical analyses showed few dependences with little statistical significance . CONCLUSIONS Cognitive rehabilitation produces moderate improvement in cognitive functioning Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE There is considerable interest in cognitive remediation for schizophrenia . Our study aim ed to evaluate , in a large sample of patients with schizophrenia , the interest of a computer-assisted cognitive remediation program on cognitive performances of patients as well as in clinical and functional outcome . METHOD Seventy-seven patients with remitted schizophrenia were r and omly assigned to 14 2-hours individual sessions of computer-assisted cognitive remediation ( n=39 ) or a control condition ( n=38 ) . Remediation was performed using RehaCom ® software . Four procedures were chosen to train four cognitive functions involved in different stages of the information processing : attention/concentration , working memory , logic , and executive functions . Primary outcomes were remediation exercise metrics , neuropsychological composites ( episodic memory , working memory , attention , executive functioning , and processing speed ) , clinical and community functioning measures . RESULTS Cognitive performances concerning Attention/vigilance , verbal working memory and verbal learning memory and reasoning/problem solving improved significantly in the remediation condition when no difference was reported in the control condition between the 2 assessment s. However , there were no significant benefits of cognitive remediation on non-verbal working memory and learning and speed of processing or functional outcome measures . CONCLUSIONS Cognitive remediation for people with schizophrenia was effective in improving performance , but the benefits of training did not generalize to functional outcome measures . Long term follow-up studies are needed to confirm the maintenance of such improvements Computerized cognitive remediation has result ed in improved executive function in schizophrenia , whereas results with regard to verbal memory were inconsistent . In the present study , 42 in patients with schizophrenia were r and omly assigned to a computerized cognitive remediation group or to a treatment-as-usual ( TAU ) control group . The remediation group received 15 sessions of computerized cognitive training ( Cogpack ) over a 3-week period . Neurocognitive functions were assessed at the beginning and end of this period . Compared to the control condition , remediation training result ed in improvements in verbal learning , processing speed and executive function ( verbal fluency ) . The results indicate that cognitive remediation may lead to improvements beyond those of executive function Abstract Objective . Adherence to prescribed antipsychotic medication is a major factor in achieving optimal long-term clinical outcomes . The aim of this study was to evaluate the impact of a telephone-based strategy provided by a nurse on adherence to antipsychotic treatment among patients with schizophrenia . Methods . A total of 928 clinical ly stable out patients with schizophrenia were r and omized to receive a monthly telephone call by a nurse or routine clinical care . Telephone calls were performed at weeks 4 , 8 , and 12 , consisting of a st and ardized interview to detect and assess therapeutic adherence and subjective attitude towards medication . Patients were followed for 4 months . A cut-point of ≥ 60 % of prescribed dose was used to classify patients as being adherent . Results . At week 16 , a significantly higher percentage of patients who received a telephone-based follow-up ( 96.7 % , n = 410 ) were classified as adherent compared to the control group ( 91.2 % , n = 402 ) ( P = 0.0007 ) . Patients in the intervention group were significantly more likely to be adherent than control group ( adjusted OR = 3.3 95 % CI 1.6–6.6 , P = 0.0001 ) . Conclusions . Telephone-based nursing strategy showed a significant improvement in adherence to antipsychotic drugs . Further studies are necessary to confirm if this kind of intervention could be a complementary strategy to optimize adherence in patients with schizophrenia Although social skills training ( SST ) is an effective approach for improving social skills for schizophrenia , the motivational deficit attenuates its efficacy . Virtual reality ( VR ) applications have allowed individuals with mental disabilities to enhance their motivation for rehabilitation . We compared SST using VR role-playing ( SST-VR ) to SST using traditional role-playing ( SST-TR ) . This r and omized , controlled trial included 91 in patients with schizophrenia who were assigned to either SST-VR ( n=46 ) or SST-TR ( n=45 ) . Both groups were administered over 10 semiweekly group sessions . An experienced , blinded rater assessed vocal , nonverbal and conversational skills . We also obtained data on motivation for SST and various social abilities . Throughout the 10 sessions , the SST-VR group ( n=33 ) showed greater interest in SST and generalization of the skills than the SST-TR group ( n=31 ) . After SST , the SST-VR group improved more in conversational skills and assertiveness than the SST-TR group , but less in nonverbal skills . The VR application in role-plays of SST for schizophrenia may be particularly beneficial in terms of improving the conversational skills and assertiveness , possibly through its advantages in enhancing motivation for SST and generalization of the skills , and thus it may be a useful supplement to traditional SST Deprivation of liberty ( DL ) in psychiatric inpatient care is common worldwide . As liberty is a central element of patients ’ rights , there is a need to develop most effective methods supporting patients ’ personal liberty . The article presents initial results from a Output:	Computer-assisted cognitive rehabilitation was effective in improving cognitive function . Specific technology types have been found to be effective for some outcomes ( eg , telephone and remote medication monitoring for adherence to treatment ) , while other types of telehealth technologies ( eg , delivery of patient education using computers ) had no benefit over traditional nurse-based methods and were less acceptable to patients .
MS21966	*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 In light of the increasing rate of dengue infections throughout the world despite vector-control measures , several dengue vaccine c and i date s are in development . METHODS In a phase 3 efficacy trial of a tetravalent dengue vaccine in five Latin American countries where dengue is endemic , we r and omly assigned healthy children between the ages of 9 and 16 years in a 2:1 ratio to receive three injections of recombinant , live , attenuated , tetravalent dengue vaccine ( CYD-TDV ) or placebo at months 0 , 6 , and 12 under blinded conditions . The children were then followed for 25 months . The primary outcome was vaccine efficacy against symptomatic , virologically confirmed dengue ( VCD ) , regardless of disease severity or serotype , occurring more than 28 days after the third injection . RESULTS A total of 20,869 healthy children received either vaccine or placebo . At baseline , 79.4 % of an immunogenicity subgroup of 1944 children had seropositive status for one or more dengue serotypes . In the per- protocol population , there were 176 VCD cases ( with 11,793 person-years at risk ) in the vaccine group and 221 VCD cases ( with 5809 person-years at risk ) in the control group , for a vaccine efficacy of 60.8 % ( 95 % confidence interval [ CI ] , 52.0 to 68.0 ) . In the intention-to-treat population ( those who received at least one injection ) , vaccine efficacy was 64.7 % ( 95 % CI , 58.7 to 69.8 ) . Serotype-specific vaccine efficacy was 50.3 % for serotype 1 , 42.3 % for serotype 2 , 74.0 % for serotype 3 , and 77.7 % for serotype 4 . Among the severe VCD cases , 1 of 12 was in the vaccine group , for an intention-to-treat vaccine efficacy of 95.5 % . Vaccine efficacy against hospitalization for dengue was 80.3 % . The safety profile for the CYD-TDV vaccine was similar to that for placebo , with no marked difference in rates of adverse events . CONCLUSIONS The CYD-TDV dengue vaccine was efficacious against VCD and severe VCD and led to fewer hospitalizations for VCD in five Latin American countries where dengue is endemic . ( Funded by Sanofi Pasteur ; Clinical Trials.gov number , NCT01374516 . ) Background : The dengue virus is a member of the Flavivirus ( FV ) genus , which also includes the yellow fever virus . Dengue disease is caused by any 1 of 4 dengue virus serotypes and is a serious public health concern in Latin America . This study evaluated the safety and immunogenicity of a c and i date recombinant , live-attenuated , tetravalent dengue vaccine ( CYD-TDV ) in 9–16 year olds in Latin America . Methods : In this r and omized , blinded , controlled study , volunteers received either 3 doses of CYD-TDV ( n = 401 ) or placebo as first and second injection and tetanus/diphtheria/acellular pertussis vaccine as third injection ( n = 199 ) at 0 , 6 and 12 months . Adverse events were documented . Plaque reduction neutralization test antibody titers against the 4 CYD-TDV parental strains were measured before and 28 days after each dose . Seropositivity was defined as antibody titers ≥10 1/dil . Results : The number of adverse reactions decreased after each successive CYD-TDV dose . After each CYD-TDV dose , antibody titers against all 4 serotypes were higher than baseline and respective predose titers . After the third dose of CYD-TDV , 100 % , 98.6 % and 93.4 % of participants were seropositive for at least 2 , at least 3 or all 4 serotypes , respectively . Higher antibody titers were observed in participants in the CYD-TDV group who were FV-seropositive at baseline compared with those who were FV-seronegative . Conclusions : CYD-TDV had a favorable safety profile and elicited antibody responses against all 4 dengue virus serotypes in 9–16 year olds in Latin America . These findings support the continued development of CYD-TDV Immunogenicity and safety of a recombinant , live-attenuated , tetravalent dengue disease vaccine ( CYD-TDV ) was evaluated in children/adolescents in Brazil . In this observer-blind , placebo-controlled , phase II single-center study , children/adolescents ( ages 9–16 years ) were r and omized to receive CYD-TDV or placebo at 0 , 6 , and 12 months . Immunogenicity was assessed using a 50 % plaque neutralization test . Overall , 150 participants were enrolled ( CYD-TDV : N = 100 ; placebo : N = 50 ) . Injection site pain and headache were the most common solicited injection site and systemic reactions . Unsolicited adverse events ( AEs ) and serious AEs were similar between groups . No serious AEs were vaccine-related . Geometric mean titers against all dengue virus serotypes increased with CYD-TDV vaccination and were 267 , 544 , 741 , and 432 1/dil for serotypes 1–4 , respectively , after dose 3 , representing a mean fold increase from baseline of 5 , 6 , 6 , and 20 , respectively . CYD-TDV vaccination elicited a neutralizing antibody response against serotypes 1–4 and was well-tolerated in children/adolescents in a dengue-endemic region BACKGROUND Roughly half the world 's population live in dengue-endemic countries , but no vaccine is licensed . We investigated the efficacy of a recombinant , live , attenuated tetravalent dengue vaccine . METHODS In this observer-masked , r and omised , controlled , monocentre , phase 2b , proof-of-concept trial , healthy Thai schoolchildren aged 4 - 11 years were r and omly assigned ( 2:1 ) to receive three injections of dengue vaccine or control ( rabies vaccine or placebo ) at months 0 , 6 , and 12 . R and omisation was by computer-generated permuted blocks of six and participants were assigned with an interactive response system . Participants were actively followed up until month 25 . All acute febrile illnesses were investigated . Dengue viraemia was confirmed by serotype-specific RT-PCR and non-structural protein 1 ELISA . The primary objective was to assess protective efficacy against virologically confirmed , symptomatic dengue , irrespective of severity or serotype , occurring 1 month or longer after the third injection ( per- protocol analysis ) . This trial is registered at Clinical Trials.gov , NCT00842530 . FINDINGS 4002 participants were assigned to vaccine ( n=2669 ) or control ( n=1333 ) . 3673 were included in the primary analysis ( 2452 vaccine , 1221 control ) . 134 cases of virologically confirmed dengue occurred during the study . Efficacy was 30·2 % ( 95 % CI -13·4 to 56·6 ) , and differed by serotype . Dengue vaccine was well tolerated , with no safety signals after 2 years of follow-up after the first dose . INTERPRETATION These data show for the first time that a safe vaccine against dengue is possible . Ongoing large-scale phase 3 studies in various epidemiological setting s will provide pivotal data for the CYD dengue vaccine c and i date . FUNDING Sanofi Pasteur BACKGROUND A c and i date tetravalent dengue vaccine is being assessed in three clinical trials involving more than 35,000 children between the ages of 2 and 16 years in Asian-Pacific and Latin American countries . We report the results of long-term follow-up interim analyses and integrated efficacy analyses . METHODS We are assessing the incidence of hospitalization for virologically confirmed dengue as a surrogate safety end point during follow-up in years 3 to 6 of two phase 3 trials , CYD14 and CYD15 , and a phase 2b trial , CYD23/57 . We estimated vaccine efficacy using pooled data from the first 25 months of CYD14 and CYD15 . RESULTS Follow-up data were available for 10,165 of 10,275 participants ( 99 % ) in CYD14 and 19,898 of 20,869 participants ( 95 % ) in CYD15 . Data were available for 3203 of the 4002 participants ( 80 % ) in the CYD23 trial included in CYD57 . During year 3 in the CYD14 , CYD15 , and CYD57 trials combined , hospitalization for virologically confirmed dengue occurred in 65 of 22,177 participants in the vaccine group and 39 of 11,089 participants in the control group . Pooled relative risks of hospitalization for dengue were 0.84 ( 95 % confidence interval [ CI ] , 0.56 to 1.24 ) among all participants , 1.58 ( 95 % CI , 0.83 to 3.02 ) among those under the age of 9 years , and 0.50 ( 95 % CI , 0.29 to 0.86 ) among those 9 years of age or older . During year 3 , hospitalization for severe dengue , as defined by the independent data monitoring committee criteria , occurred in 18 of 22,177 participants in the vaccine group and 6 of 11,089 participants in the control group . Pooled rates of efficacy for symptomatic dengue during the first 25 months were 60.3 % ( 95 % CI , 55.7 to 64.5 ) for all participants , 65.6 % ( 95 % CI , 60.7 to 69.9 ) for those 9 years of age or older , and 44.6 % ( 95 % CI , 31.6 to 55.0 ) for those younger than 9 years of age . CONCLUSIONS Although the unexplained higher incidence of hospitalization for dengue in year 3 among children younger than 9 years of age needs to be carefully monitored during long-term follow-up , the risk among children 2 to 16 years of age was lower in the vaccine group than in the control group . ( Funded by Sanofi Pasteur ; Clinical Trials.gov numbers , NCT00842530 , NCT01983553 , NCT01373281 , and NCT01374516 . ) Output:	Most of the vaccinated individuals had previous immunity for at least one serotype , which generated safety concerns in individuals without previous immunity . Conclusions Compared with other commercially available vaccines , the dengue vaccine showed poor efficacy
MS21967	*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 Cognitive impairment after critical illness is common and debilitating . We developed a cognitive therapy program for critically ill patients and assessed the feasibility and safety of administering combined cognitive and physical therapy early during a critical illness . Methods We r and omized 87 medical and surgical ICU patients with respiratory failure and /or shock in a 1:1:2 manner to three groups : usual care , early once-daily physical therapy , or early once-daily physical therapy plus a novel , progressive , twice-daily cognitive therapy protocol . Cognitive therapy included orientation , memory , attention , and problem-solving exercises , and other activities . We assessed feasibility outcomes of the early cognitive plus physical therapy intervention . At 3 months , we also assessed cognitive , functional , and health-related quality of life outcomes . Data are presented as median ( interquartile range ) or frequency ( % ) . Results Early cognitive therapy was a delivered to 41/43 ( 95 % ) of cognitive plus physical therapy patients on 100 % ( 92–100 % ) of study days beginning 1.0 ( 1.0–1.0 ) day following enrollment . Physical therapy was received by 17/22 ( 77 % ) of usual care patients , by 21/22 ( 95 % ) of physical therapy only patients , and 42/43 ( 98 % ) of cognitive plus physical therapy patients on 17 % ( 10–26 % ) , 67 % ( 46–87 % ) , and 75 % ( 59–88 % ) of study days , respectively . Cognitive , functional , and health-related quality of life outcomes did not differ between groups at 3-month follow-up . Conclusions This pilot study demonstrates that early rehabilitation can be extended beyond physical therapy to include cognitive therapy . Future work to determine optimal patient selection , intensity of treatment , and benefits of cognitive therapy in the critically ill is needed Purpose : The purpose of this review is to evaluate the literature related to mobilization of the critically ill patient with an emphasis on functional outcomes and patient safety . Methods : We search ed the electronic data bases of PubMed , CINAHL , Medline ( Ovid ) , and The Cochrane Library for a period spanning 2000‐2011 . Articles used in this review included r and omized and nonr and omized clinical trials , prospect i ve and retrospective analyses , and case series in peer review ed journals . Sackett 's Levels of Evidence were used to classify the current literature to evaluate the strength of the outcomes reported . Results : Fifteen studies met inclusion criteria and were review ed . According to Sackett 's Levels of Evidence , 9 studies were level 4 evidence , one study was level 3 , 4 studies were level 2 , and one study was level one evidence . Ten studies pertained to patient safety/feasibility and 10 studies pertained to functional outcomes with 5 fitting into both categories . Conclusion : A search of the scientific literature revealed a limited number of studies that examined the mobilization of critically ill patients in the intensive care unit . However , literature that does exist supports early mobilization and physical therapy as a safe and effective intervention that can have a significant impact on functional outcomes Objectives : To investigate whether a daily exercise session , using a bedside cycle ergometer , is a safe and effective intervention in preventing or attenuating the decrease in functional exercise capacity , functional status , and quadriceps force that is associated with prolonged intensive care unit stay . A prolonged stay in the intensive care unit is associated with muscle dysfunction , which may contribute to an impaired functional status up to 1 yr after hospital discharge . No evidence is available concerning the effectiveness of an early exercise training intervention to prevent these detrimental complications . Design : R and omized controlled trial . Setting : Medical and surgical intensive care unit at University Hospital Gasthuisberg . Patients : Ninety critically ill patients were included as soon as their cardiorespiratory condition allowed bedside cycling exercise ( starting from day 5 ) , given they still had an expected prolonged intensive care unit stay of at least 7 more days . Interventions : Both groups received respiratory physiotherapy and a daily st and ardized passive or active motion session of upper and lower limbs . In addition , the treatment group performed a passive or active exercise training session for 20 mins/day , using a bedside ergometer . Measurements and Main Results : All outcome data are reflective for survivors . Quadriceps force and functional status were assessed at intensive care unit discharge and hospital discharge . Six-minute walking distance was measured at hospital discharge . No adverse events were identified during and immediately after the exercise training . At intensive care unit discharge , quadriceps force and functional status were not different between groups . At hospital discharge , 6-min walking distance , isometric quadriceps force , and the subjective feeling of functional well-being ( as measured with “ Physical Functioning ” item of the Short Form 36 Health Survey question naire ) were significantly higher in the treatment group ( p < .05 ) . Conclusions : Early exercise training in critically ill intensive care unit survivors enhanced recovery of functional exercise capacity , self-perceived functional status , and muscle force at hospital discharge Introduction The purpose of this trial was to investigate the effectiveness of an exercise rehabilitation program commencing during ICU admission and continuing into the outpatient setting compared with usual care on physical function and health-related quality of life in ICU survivors . Methods We conducted a single-center , assessor-blinded , r and omized controlled trial . One hundred and fifty participants were stratified and r and omized to receive usual care or intervention if they were in the ICU for 5 days or more and had no permanent neurological insult . The intervention group received intensive exercises in the ICU and the ward and as out patients . Participants were assessed at recruitment , ICU admission , hospital discharge and at 3- , 6- and 12-month follow-up . Physical function was evaluated using the Six-Minute Walk Test ( 6MWT ) ( primary outcome ) , the Timed Up and Go Test and the Physical Function in ICU Test . Patient-reported outcomes were measured using the Short Form 36 Health Survey , version 2 ( SF-36v2 ) and Assessment of Quality of Life ( AQoL ) Instrument . Data were analyzed using mixed models . Results The a priori enrollment goal was not reached . There were no between-group differences in demographic and hospital data , including acuity and length of acute hospital stay ( LOS ) ( Acute Physiology and Chronic Health Evaluation II score : 21 vs 19 ; hospital LOS : 20 vs 24 days ) . No significant differences were found for the primary outcome of 6MWT or any other outcomes at 12 months after ICU discharge . However , exploratory analyses showed the rate of change over time and mean between-group differences in 6MWT from first assessment were greater in the intervention group . Conclusions Further research examining the trajectory of improvement with rehabilitation is warranted in this population .Trial registration The trial was registered with the Australian New Zeal and Clinical Trials Registry ACTRN12605000776606 ABSTRACT Objective : To evaluate the effects that passive cycling exercise , in combination with conventional physical therapy , have on peripheral muscle strength , duration of mechanical ventilation , and length of hospital stay in critically ill patients admitted to the ICU of a tertiary care university hospital . Methods : This was a r and omized clinical trial involving 38 patients ( ≥ 18 years of age ) on mechanical ventilation who were r and omly divided into two groups : control ( n = 16 ) , receiving conventional physical therapy ; and intervention ( n = 22 ) , receiving conventional physical therapy and engaging in passive cycling exercise five days per week . The mean age of the patients was 46.42 ± 16.25 years , and 23 were male . The outcomes studied were peripheral muscle strength , as measured by the Medical Research Council scale , duration of mechanical ventilation , and length of hospital stay . Results : There was a significant increase in peripheral muscle strength ( baseline vs. final ) in both groups ( control : 40.81 ± 7.68 vs. 45.00 ± 6.89 ; and intervention : 38.73 ± 11.11 vs. 47.18 ± 8.75 ; p < 0.001 for both ) . However , the range of increase in strength was higher in the intervention group than in the control group ( 8.45 ± 5.20 vs. 4.18 ± 2.63 ; p = 0.005 ) . There were no significant differences between the groups in terms of duration of mechanical ventilation or length of hospital stay . Conclusions : The results suggest that the performance of continuous passive mobilization on a cyclical basis helps to recover peripheral muscle strength in ICU patients . ( Clinical Trials.gov Identifier : NCT01769846 [ http://www . clinical trials.gov/ ] Background : Systematic review s of early rehabilitation within intensive care units have highlighted the need for robust multi‐centre r and omised controlled trials with longer term follow up . This trial aims to explore the feasibility of earlier and enhanced rehabilitation for patients mechanically ventilated for ≥5 days and to assess the impact on possible long term outcome measures for use in a definitive trial . Methods : Patients admitted to a large UK based intensive care unit and invasively ventilated for ≥5 days were r and omised to the rehabilitation intervention or st and ard care on a 1:1 basis , stratified by age and SOFA score . The rehabilitation intervention involved a structured programme , with progression along a functionally based mobility protocol according to set safety criteria . Results : 103 out of 128 eligible patients were recruited into the trial , achieving an initial recruitment rate of 80 % . Patients in the intervention arm mobilized significantly earlier ( 8 days vs 10 days , p = 0.035 ) , at a more acute phase of illness ( SOFA 6 vs 4 , p < 0.05 ) and reached a higher level of mobility at the point of critical care discharge ( MMS 7 vs 5 , p < 0.01 ) . Conclusion : We have demonstrated the feasibility of introducing a structured programme of rehabilitation for patients admitted to critical care . HighlightsThe introduction of an earlier and enhanced rehabilitation was feasible for patients ' ventilated ≥5 daysWhen introduced , patients were mobilised earlier and in a more acute phase of their illness , Earlier mobilisation led to patients achieving higher levels of mobility at the point of critical care dischargeThis positive impact was seen despite the previous successful implementation of a quality improvement project in the BACKGROUND muscle wasting is associated with a detrimental outcome in older people . Muscle strength measurements could be useful as part of a clinical evaluation of oldest old patients to determine who are most at risk of accelerated decline in the near future . OBJECTIVE this study aim ed to assess if h and grip strength predicts changes in functional , psychological and social health among oldest old . DESIGN the Leiden 85-plus Study is a prospect i ve population -based follow-up study . SUBJECTS five-hundred fifty-five , all aged 85 years at baseline , participated in the study . METHODS h and grip strength was measured with a h and grip strength dynamometer . Functional , psychological and social health were assessed annually . Baseline data on chronic diseases were obtained from the treating physician , pharmacist , electrocardiogram and blood sample analysis . RESULTS at age 85 , lower h and grip strength was correlated with poorer scores in functional , psychological and social health domains ( all , P < 0.001 ) . Lower baseline h and grip strength predicted an accelerated decline in activities of daily living ( ADL ) and cognition ( both , P < or= 0.001 ) , but not in social health ( P > 0.30 ) . CONCLUSION poor h and grip strength predicts accelerated dependency in ADL and cognitive decline in oldest old . Measuring h and grip strength could be a useful instrument in geriatric practice to identify those oldest old patients at risk for this accelerated decline BACKGROUND Immobilisation predicts adverse outcomes in patients in the surgical intensive care unit ( SICU ) . Attempts to mobilise critically ill patients early after surgery are frequently restricted , but we tested whether early mobilisation leads to improved mobility , decreased SICU length of stay , and increased functional independence of patients at hospital discharge . METHODS We did a multicentre , international , parallel-group , assessor-blinded , r and omised controlled trial in SICUs of five university hospitals in Austria ( n=1 ) , Germany ( n=1 ) , and the USA ( n=3 ) . Eligible patients ( aged 18 years or older , who had been mechanically ventilated for < 48 h , and were expected to require mechanical ventilation for ≥24 h ) were r and omly assigned ( 1:1 ) by use of a stratified block r and omisation via restricted web platform to st and ard of care ( control ) or early , goal -directed mobilisation using an inter-professional approach of closed-loop communication and the SICU optimal mobilisation score ( SOMS ) algorithm ( intervention ) , which describes patients ' mobilisation capacity on a numerical rating scale ranging from 0 ( no mobilisation ) to 4 ( ambulation ) . We had three main outcomes hierarchically tested in a prespecified order : the mean SOMS level patients achieved during their SICU stay ( primary outcome ) , and patient 's length of stay on SICU and the mini-modified functional independence measure score ( mmFIM ) at hospital discharge ( both secondary outcomes ) . This trial is registered with Clinical Trials.gov ( NCT01363102 ) . FINDINGS Between July 1 , 2011 , and Nov 4 , 2015 , we r and omly assigned 200 patients to receive st and ard treatment ( control ; n=96 ) or intervention ( n=104 ) . Intention-to-treat analysis showed that the intervention improved the mobilisation level ( Output:	Early mobilization appears to decrease the incidence of ICU-AW , improve the functional capacity , and increase the number of ventilator-free days and the discharged-to-home rate for patients with a critical illness in the ICU setting
MS21968	*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 did a prospect i ve study of women with singleton viable pregnancies at 10 - 13 weeks ' gestation who requested first-trimester fetal karyotyping because of advanced maternal age , parental anxiety , or family history of chromosomal abnormality . Women were counselled as to the available options of non-invasive screening or invasive testing by mid-trimester amniocentesis , early amniocentesis ( EA ) , or chorionic villus sampling ( CVS ) , or r and omisation to EA or CVS at 10 - 13 weeks . EA was done in 731 patients ( 493 by choice and 238 by r and omisation ) and CVS in 570 ( 320 by choice and 250 by r and omisation ) . Both procedures were done by transabdominal ultrasound-guided insertion of a 20-gauge needle . The rate of successful sampling was the same for both procedures ( 97.5 % ) . Spontaneous loss ( intrauterine or neonatal death ) was significantly higher after EA ( total group mean = 5.3 % , 95 % CI 3.8 - 7.2 ; r and omised subgroup mean = 5.9 % , 3.3 - 9.7 ) than after CVS ( total group : mean = 2.3 % , 1.2 - 3.9 ; r and omised subgroup : mean = 1.2 % , 0.3 - 3.5 ) . The gestation at delivery and birthweight of the infants after EA and CVS were similar . In the EA group the incidence of talipes equinovarus ( 1.63 % ) , was higher than in the CVS group ( 0.56 % ) , but this difference was not significant BACKGROUND Acute rejection episodes after renal transplantation are an important clinical challenge , despite use of multidrug immunosuppressive regimens . We did a prospect i ve , multicentre , r and omised , double-blind trial to investigate the impact of the addition of sirolimus , compared with azathioprine , to a cyclosporin and prednisone regimen . METHODS 719 recipients of primary HLA-mismatched cadaveric or living-donor renal allografts who displayed initial graft function were r and omly assigned , after transplantation , sirolimus 2 mg daily ( n=284 ) or 5 mg daily ( n=274 ) , or azathioprine ( n=161 ) . We assessed the primary composite endpoint of efficacy failure , occurrence of biopsy-confirmed acute rejection episodes , graft loss , or death , and various secondary endpoints that characterise these episodes at 6 months and 12 months . Analyses were done by intention to treat . FINDINGS The rate of efficacy failure at 6 months was lower in the two sirolimus groups ( 2 mg 18.7 % , p=0.002 ; 5 mg 16.8 % , p<0.001 ) than in the azathioprine group ( 32.3 % ) . The frequency of biopsy-confirmed acute rejection episodes was also lower ( 2 mg 16.9 % , p=0.002 ; 5 mg 12.0 % , p<0.001 ; azathioprine 29.8 % ) . At 12 months , survival was similar in all groups for grafts ( 97.2 % , 96.0 % , and 98.1 % ) and patients ( 94.7 % , 92.7 % , and 93.8 % ) . Patients on sirolimus showed a delay in the time to first acute rejection episode and decreased frequency of moderate and severe histological grade s of rejection episodes and related antibody treatment , compared with the azathioprine group . Rates of infection and malignant disorders were similar in all groups . INTERPRETATION Use of sirolimus reduced occurrence and severity of biopsy-confirmed acute rejection episodes with no increase in complications . Further studies are needed to establish the optimum doses for the combined regimen OBJECTIVES To compare the clinical - and cost-effectiveness of minimally invasive direct coronary artery bypass grafting ( MIDCAB ) and percutaneous transluminal coronary angioplasty ( PTCA ) with or without stenting in patients with single-vessel disease of the left anterior descending coronary artery ( LAD ) . DESIGN Multi-centre r and omised trial without blinding . The computer-generated sequence of r and omised assignments was stratified by centre , allocated participants in blocks and was concealed using a central ised telephone facility . SETTING Four tertiary cardiothoracic surgery centres in Engl and . PARTICIPANTS Patients with ischaemic heart disease with at least 50 % proximal stenosis of the LAD , suitable for either PTCA or MIDCAB , and with no significant disease in another vessel . INTERVENTIONS Patients r and omised to PTCA had local anaesthetic and underwent PTCA according to the method preferred by the operator carrying out the procedure . Patients r and omised to MIDCAB had general anaesthetic . The chest was opened through an 8 - 10-cm left anterior thoracotomy . The ribs were retracted and the left internal thoracic artery ( LITA ) harvested . The pericardium was opened in the line of the LAD to confirm the feasibility of operation . The distal LITA was anastomosed end-to-side to an arteriotomy in the LAD . All operators were experienced in carrying out MIDCAB . MAIN OUTCOME MEASURES The primary outcome measure was survival free from cardiac-related events . Relevant events were death , myocardial infa rct ion , repeat coronary revascularisation and recurrence of symptomatic angina or clinical signs of ischaemia during an exercise tolerance test at annual follow-up . Secondary outcome measures were complications , functional outcome , disease-specific and generic quality of life , health and social services re source use and their costs . RESULTS A total of 12,828 consecutive patients undergoing an angiogram were logged at participating centres from November 1999 to December 2001 . Of the 1091 patients with proximal stenosis of the LAD , 127 were eligible and consented to take part ; 100 were r and omised and the remaining 27 consented to follow-up . All r and omised participants were included in an intention-to-treat analysis of survival free from cardiac-related events , which found a non-significant benefit from MIDCAB . Cumulative hazard rates at 12 months were estimated to be 7.1 and 9.2 % for MIDCAB and PTCA , respectively . There were no important differences between MIDCAB and PTCA with respect to angina symptoms or disease-specific or generic quality of life . The total NHS procedure costs were 1648 British pounds and 946 British pounds for MIDCAB and PTCA , respectively . The costs of re sources used during 1 year of follow-up were 1033 British pounds and 843 British pounds , respectively . CONCLUSIONS The study found no evidence that MIDCAB was more effective than PTCA . The procedure costs of MIDCAB were observed to be considerably higher than those of PTCA . Given these findings , it is unlikely that MIDCAB represents a cost-effective use of re sources in the reference population . Recent advances in cardiac surgery mean that surgeons now tend to carry out off-pump bypass grafting via a sternotomy instead of MIDCAB . At the same time , cardiologists are treating more patients with multi-vessel disease by PTCA . Future primary research should focus on this comparison . Other small trials of PTCA versus MIDCAB have now finished and a more conclusive answer to the original objective could be provided by a systematic review The Emory Angioplasty versus Surgery Trial ( EAST ) showed that multivessel patients eligible for both percutaneous transluminal coronary angioplasty ( PTCA ) and coronary bypass surgery ( CABG ) had equivalent 3-year outcomes regarding survival , myocardial infa rct ion , and major myocardial ischemia . Patients eligible for the trial who were not r and omized because of physician or patient refusal were followed in a registry . This study compares the outcomes of the r and omized and registry patients . Of the 842 eligible patients , 450 did not enter the trial . Their baseline features closely resembled those of the r and omized patients and follow up was performed using the same methods . In the registry there was a bias toward selecting CABG in patients with 3-vessel disease ( 84 % ) and PTCA in patients with 2-vessel disease ( 54 % ) . Three-year survival for the registry patients was 96.4 % , which was better than the r and omized patients , 93.4 % ( p = 0.044 ) . Angina relief in the registry was equal for CABG and PTCA patients and was better for the PTCA registry ( 12.4 % ) than PTCA r and omized patients ( 19.6 % ) ( p = 0.079 ) . Thus , the registry confirms that EAST is representative of all eligible patients and does not represent a low-risk subgroup . Since baseline differences were small , improved survival in the registry may be due to treatment selection . Physician judgment , even in patients judged appropriate for clinical trials , remains a potentially important predictor of outcomes OBJECTIVES This study was done to compare characteristics and outcomes of patients with acute myocardial infa rct ion participating in two thrombolysis trials with those of nontrial patients at study hospitals and external hospitals . BACKGROUND Preferential recruitment of lower risk patients into r and omized trials of thrombolysis has been suggested by earlier studies . However , to date there has not been a definitive population -based comparison of characteristics and outcomes for thrombolysis trial participants and non participants . METHODS Population -based data on hospital admissions and mortality from acute myocardial infa rct ion for all hospitals in Ontario from 1989 to 1992 were linked to data on trial participants in two distinct thrombolysis studies ( GUSTO I and LATE ) . Included were 1,304 patients entered into GUSTO , 12,657 non participants at GUSTO hospitals , 249 patients entered into LATE , 5,997 non participants at LATE hospitals and 12,299 patients at external hospitals . The main outcomes were differences in age , gender , comorbidity scores , coronary revascularization and survival to hospital discharge . RESULTS Patients in both GUSTO and LATE were significantly more likely to be < 70 years old ( odds ratio [ OR ] 2.8 and 3.2 , respectively ) , to be male ( OR 2.0 and 2.1 , respectively ) , to have low comorbidity scores ( OR 2.0 and 2.3 , respectively ) and , for GUSTO alone , to undergo coronary revascularization ( OR 2.4 ) . Nontrial patients were similar between trial hospitals and external hospitals . In-hospital mortality rates for GUSTO and LATE patients were lower ( 6.9 % and 6.6 % , respectively ) than for non participants at study hospitals ( 16.8 % and 19.7 % , respectively ; p<0.001 for both comparisons ) . Survival to hospital discharge remained higher among GUSTO ( OR 1.9 ) and LATE patients ( OR 2.0 ) than non participants at study hospitals even after adjustment for age , gender , revascularization and comorbidity scores . CONCLUSIONS Compared with nontrial patients , thrombolysis trial participants are younger , more often male , undergo more revascularization and have less comorbid disease . Even after adjustment for these factors , participants have a survival advantage over non participants that is larger than expected from thrombolysis alone . These findings are not attributable to inferior care or skewed population s at hospitals that did not join these major trials . Further study of these selection biases may guide future trial design and deepen our underst and ing of why thrombolytics have been underused for high risk patients in routine practice The Coronary Artery Surgery Study ( CASS ) includes 780 patients with mild or moderate stable angina pectoris or asymptomatic survivors of a myocardial infa rct ion who were r and omized to either medical or surgical therapy and 1,319 patients who were eligible for r and omization but were not r and omized ( r and omizable patients ) . There were no substantial aggregate differences observed in any of the survival comparisons after 10 years of follow-up study between the r and omized and r and omizable patients assigned to the medical ( 79 % versus 80 % ) or surgical ( 82 % versus 81 % ) groups or in patient subgroups stratified according to coronary artery disease extent and left ventricular ejection fraction . Cox regression analyses were done with independent variables known to be predictors of survival , including surgical versus medical therapy and r and omized versus r and omizable group , to test the null hypothesis of a mortality difference between medical versus surgical assignment according to group assignment ( r and omized versus r and omizable ) . In no case did the initial group category enter as a significant predictor of survival . The results in the r and omizable group reinforce those in the r and omized group with respect to the medical versus surgical comparison . Two subgroups are identified with a significant surgical advantage : 1 ) patients with proximal left anterior descending coronary artery stenosis greater than or equal to 70 % and an ejection fraction less than 0.50 , and 2 ) patients with three vessel coronary artery disease and an ejection fraction less than 0.50 . In both groups , coronary bypass surgery had a statistically significant beneficial effect on survival ( p less than 0.05 ) . After a decade of follow-up Output:	This review indicates that participation in RCTs is associated with similar outcomes to receiving the same treatment outside RCTs .
MS21969	*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 assessed the safety of the multikinase inhibitor regorafenib in patients with hepatocellular carcinoma ( HCC ) that had progressed following first-line sorafenib . PATIENTS AND METHODS Thirty-six patients with Barcelona Clinic Liver Cancer stage B or C HCC and preserved to mildly impaired liver function ( Child-Pugh class A ) received regorafenib 160 mg once daily in cycles of 3 weeks on/1 week off treatment until disease progression , unacceptable toxicity , death or patient/physician decision to discontinue . The primary end-point was safety ; secondary end-points included efficacy ( including time to progression and overall survival ) . RESULTS The median treatment duration was 19.5 weeks ( range 2 - 103 ) . At data cutoff , three patients remained on treatment . Reasons for discontinuation were adverse events ( n=20 ) , disease progression ( n=10 ) , consent withdrawal ( n=2 ) and death ( n=1 ) . Seventeen patients required dose reductions ( mostly for adverse events [ n=15 ] ) ; 35 patients had treatment interruption ( mostly for adverse events [ n=32 ] or patient error [ n=11 ] ) . The most frequent treatment-related adverse events were h and -foot skin reaction ( any grade n=19 ; grade ≥3 n=5 ) , diarrhoea ( n=19 ; n=2 ) , fatigue ( n=19 ; n=6 ) , hypothyroidism ( n=15 ; n=0 ) , anorexia ( n=13 ; n=0 ) , hypertension ( n=13 ; n=1 ) , nausea ( n=12 ; n=0 ) and voice changes ( n=10 ; n=0 ) . Disease control was achieved in 26 patients ( partial response n=1 ; stable disease n=25 ) . Median time to progression was 4.3 months . Median overall survival was 13.8 months . CONCLUSION Regorafenib had acceptable tolerability and evidence of antitumour activity in patients with intermediate or advanced HCC that progressed following first-line sorafenib Summary Background The combination of bevacizumab ( B ) and erlotinib ( E ) has shown promising clinical outcomes as the first-line treatment of advanced HCC patients . We aim ed to evaluate the efficacy and safety of using combination of B + E in treating advanced HCC patients who had failed prior sorafenib treatment . Methods Eligible advanced HCC patients with documented radiological evidence of disease progression with sorafenib treatment were recruited . All patients received bevacizumab(B ) at 10 mg/kg every 2 weeks with erlotinib(E ) at 150 mg daily for a maximum of 6 cycles . Response assessment s using both RECIST and modified RECIST criteria were performed after every 6 weeks . The primary endpoint was clinical benefit ( CB ) rate and a Simon two-stage design was employed . Results The trial was halted in the first stage according to the pre-set statistical criteria with 10 patients recruited . The median age was 47 years ( range , 28–61 ) and all patients were in ECOG performance status 1 . Eighty percent of patients were chronic hepatitis B carriers and all patients had Child A cirrhosis . Among these 10 patients , none of the enrolled patients achieved response or stable disease . The median time-to-progression was 1.81 months ( 95 % confidence interval [ C.I. ] , 1.08–1.74 months ) and overall survival was 4.37 months ( 95 % C.I. , 1.08–11.66 months ) . Rash ( 70 % ) , diarrhea ( 50 % ) and malaise ( 40 % ) were the most commonly encountered toxicities . Conclusion The combination of B + E was well tolerated but had no activity in an unselected sorafenib-refractory advanced HCC population . Condensed abstract The combination of bevacizumab and erlotinib had no clinical activity in sorafenib-refractory HCC population Background : A phase I dose-escalating study of pazopanib was conducted to determine the maximum tolerated dose ( MTD ) , pharmacokinetic/pharmacodynamic relationships , and clinical activity in patients with advanced hepatocellular carcinoma ( HCC ) . Experimental Design : Asian patients ( N = 28 ) were dose escalated on pazopanib ( 200–800 mg ) once daily ( QD ) on 21-day cycles , with MTD as the primary endpoint using a modified 3 + 3 design . Changes in tumor vasculature were evaluated by dynamic contrast-enhanced MRI ( DCE — MRI ) . Results : Two of five patients at the 800-mg dose level experienced dose-limiting toxicities [ grade 3 aspartate aminotransferase (AST)/alanine aminotransferase ( ALT ) elevations and grade 3 malaise ] . The MTD in patients with HCC ( Child – Pugh class A ) was 600 mg QD . Diarrhea , skin hypopigmentation , and AST elevation were the most commonly reported adverse events at the MTD . Mean Cmax and area under the concentration-time curve ( AUC0–6 ) of pazopanib and its metabolites did not increase dose proportionally across the 200 to 800 mg range . Reductions in IAUGC and Ktrans were shown at all pazopanib doses evaluated , with the greatest reductions at 600 and 800 mg . Although larger DCE-MRI parameter decreases were associated with larger C24 and Cmax values , there was no constant relationship between tumor perfusion decreases measured by DCE-MRI and plasma pazopanib pharmacokinetic parameters . Overall , 19 patients ( 73 % ) had either partial response or stable disease . Conclusion : Pazopanib has a manageable safety profile in patients with advanced HCC , and 600 mg was chosen for further development of pazopanib in advanced HCCs . Moreover , pazopanib reduced tumor vessel leakage , as shown by DCE-MRI , indicating a direct effect on HCC vasculature that might be associated with its antitumor activity . Clin Cancer Res ; 17(21 ) ; 6914–23 . © 2011 AACR BACKGROUND Sorafenib has proven survival benefits in patients with advanced hepatocellular carcinoma ( HCC ) . The viability of continuing sorafenib at a higher dosage in patients who experienced radiologic disease progression was investigated . METHODS Patients who experienced disease progression while on sorafenib 400 mg twice daily were r and omized to sorafenib 600 mg twice daily ( n = 49 ) or best supportive care ( n = 52 ) . The primary end point was progression-free survival ( PFS ) . Time to progression , overall survival , and safety were also evaluated . RESULTS The study did not meet its primary end point . The difference in PFS between the sorafenib arm ( 3.91 months ) and the best supportive care arm ( 2.69 months ) did not reach statistical significance ( p = 0.086 ) . Adverse events were mainly grade 1 - 2 and similar across both groups . In the sorafenib arm , the most frequent events were diarrhea ( 80 % ) , weight loss ( 75 % ) , fatigue ( 67 % ) , h and -foot-skin reaction ( 49 % ) , abdominal pain ( 37 % ) , and stomatitis ( 26 % ) . CONCLUSIONS Escalated-dose sorafenib in patients with advanced HCC who progressed while on sorafenib , failed to provide any clinical benefit . Second-line treatment still remains an open issue to be explored in appropriate clinical trials Background : Hepatocellular carcinoma ( HCC ) is a highly vascularised and poor-prognosis tumour . NGR-hTNF is a vascular-targeting agent consisting of human tumour necrosis factor-alpha fused to the tumour-homing peptide NGR , which is able to selectively bind an aminopeptidase N overexpressed on tumour blood vessels . Methods : Twenty-seven patients with advanced-stage disease resistant to either locoregional ( 59 % ; range , 1–3 ) , systemic treatments ( 52 % ; range , 1–3 ) or both ( 33 % ) received NGR-hTNF 0.8 μg m−2 once every 3 weeks . The primary aim of the study was progression-free survival ( PFS ) . Results : No grade 3–4 treatment-related toxicities were noted . Common toxicity included mild-to-moderate , short-lived chills ( 63 % ) . Median PFS was 2.3 months ( 95 % CI : 1.7–2.9 ) . A complete response ongoing after 20 months was observed in a sorafenib-refractory patient and a partial response in a Child-Pugh class-B patient , yielding a response rate of 7 % . Six patients ( 22 % ) experienced stable disease . The disease control rate ( DCR ) was 30 % and was maintained for a median PFS time of 4.3 months . Median survival was 8.9 months ( 95 % CI : 7.5–10.2 ) . In a subset of 12 sorafenib-resistant patients , the response rate was 8 % and the median survival was 9.5 months . Conclusion : NGR-hTNF was well tolerated and showed single-agent activity in HCC . Further investigation in HCC is of interest Summary Background Sorafenib is the only systemic treatment that has shown a significant benefit in overall survival ( OS ) and in progression-free survival ( PFS ) in advanced hepatocellular carcinoma ( HCC ) patients . No st and ard of care currently exists for second-line treatment . The association of Gemcitabine-Oxaliplatine ( GEMOX ) has shown efficacy in the first-line setting . The aim of this study was to evaluate the efficacy of GEMOX after failure of at least one line of anti-angiogenic ( AA ) therapy . Patient and methods We performed a multicenter retrospective analysis of advanced HCC patients that received GEMOX chemotherapy after progression on at least one line of AA therapy . Results We analyzed a total of 40 patients that received a median of 7 cycles of GEMOX over a 6-year period . Grade 3/4 toxicity was observed in 25 % of patients , mainly neurotoxicity , thrombocytopenia and neutropenia in 12.5 % , 5 % and 5 % of patients respectively . Grade <3 toxicity was mainly hematological and neurotoxicity . In the sub-cohort of 35 patients evaluable for response , partial response was observed in 20 % of patients , while 46 % had stable disease . Median OS was 8.3 months , with a 6-month OS rate of 59 % . Median PFS was 3.1 months . Prognostic factors for OS in univariable analysis were the performance status and AFP levels at GEMOX start , and the BCLC score at diagnosis . None of these factors were prognostic for PFS or tumor response . Conclusion The GEMOX schedule seems to show clinical activity and an acceptable toxicity profile in advanced HCC patients who progressed after anti-angiogenic treatment . The observed median OS of over 8 months is encouraging in this population of heavily pretreated patients . These results would merit confirmation in a prospect i ve r and omized study The classifications of hepatocellular carcinoma ( HCC ) currently used are based on prognostic factors obtained from studies performed years ago when most tumors were diagnosed at advanced stages and the survival rates were substantially poor . Recent investigations have review ed the survival of early tumors properly selected to receive radical therapies and the natural outcome of nonsurgical HCC patients . These data enable a new staging system to be proposed , the Barcelona Clinic Liver Cancer ( BCLC ) staging classification , that comprises four stages that select the best c and i date s for the best therapies currently available . Early stage ( A ) includes patients with asymptomatic early tumors suitable for radical therapies -- resection , transplantation or percutaneous treatments . Intermediate stage ( B ) comprises patients with asymptomatic multinodular HCC . Advanced stage ( C ) includes patients with symptomatic tumors and /or an invasive tumoral pattern ( vascular invasion/extrahepatic spread ) . Stage B and C patients may receive palliative treatments/new agents in the setting of phase II investigations or r and omized controlled trials . End-stage disease ( D ) contain patients with extremely grim prognosis ( Okuda stage III or PST 3 - 4 ) that should merely receive symptomatic treatment Objectives : Hepatocellular carcinoma ( HCC ) is the fifth most common cancer worldwide . Sorafenib is considered the st and ard of care for patients with advanced HCC . Methods : We conducted a retrospective analysis of our cancer center ’s experience with sorafenib in patients with advanced HCC . Eligible patients were required to have measurable disease and were allowed to have been refractory ( with documented progression ) to prior systemic therapies before starting on sorafenib . Results : Twenty-six patients ( median age = 56 years ) who were treated at the Ohio State University with sorafenib were included in this study . Thirty-eight percent had exposure to prior systemic therapy . The median time to tumor progression was 5.4 months and the median overall survival 7 months . For the patients with exposure to prior systemic therapy , the median time to tumor progression was 9.1 months and is the median overall survival 9.83 months . There were no unexpected toxicities . Conclusion : Sorafenib has interesting activity and acceptable tolerability in patients with advanced HCC , including those who failed prior therapies Second‐line treatment options in advanced hepatocellular carcinoma ( HCC ) are limited . Axitinib , a selective potent tyrosine kinase inhibitor ( TKI ) of vascular end Output:	Reported grade 3/4 toxicities were regimen-specific and it includes hepatotoxicity , hypertension , and hematologic toxicities .
MS21970	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Introduction The objective of this study was to directly compare the safety of tocilizumab ( TCZ ) and TNF inhibitors ( TNFIs ) in rheumatoid arthritis ( RA ) patients in clinical practice . Methods This prospect i ve cohort study included RA patients starting TCZ [ TCZ group , n = 302 , 224.68 patient-years ( PY ) ] or TNFIs [ TNFI group , n = 304 , 231.01 PY ] from 2008 to 2011 in the registry of Japanese RA patients on biologics for long-term safety registry . We assessed types and incidence rates ( IRs ) of serious adverse events ( SAEs ) and serious infections ( SIs ) during the first year of treatment . Risks of the biologics for SAEs or SIs were calculated using the Cox regression hazard analysis . Results Patients in the TCZ group had longer disease duration ( P < 0.001 ) , higher disease activity ( P = 0.019 ) and more frequently used concomitant corticosteroids ( P < 0.001 ) than those in the TNFI group . The crude IR ( /100 PY ) of SIs [ TCZ 10.68 vs. TNFI 3.03 ; IR ratio ( 95 % confidence interval [ CI ] ) , 3.53 ( 1.52 to 8.18 ) ] , but not SAEs [ 21.36 vs. 14.72 ; 1.45 ( 0.94 to 2.25 ) ] , was significantly higher in the TCZ group compared with the TNFI group . However , after adjusting for covariates using the Cox regression hazard analysis , treatment with TCZ was not associated with higher risk for SAEs [ hazard ratio ( HR ) 1.28 , 95 % CI 0.75 to 2.19 ] or SIs ( HR 2.23 , 95 % CI 0.93 to 5.37 ) . Conclusions The adjusted risks for SAEs and SIs were not significantly different between TCZ and TNFIs , indicating an influence of clinical characteristics of the patients on the safety profile of the biologics in clinical practice CONTEXT High levels of lipoprotein(a ) are associated with increased risk of myocardial infa rct ion ( MI ) . OBJECTIVE To assess whether genetic data are consistent with this association being causal . DESIGN , SETTING , AND PARTICIPANTS Three studies of white individuals from Copenhagen , Denmark , were used : the Copenhagen City Heart Study ( CCHS ) , a prospect i ve general population study with 16 years of follow-up ( 1991 - 2007 , n = 8637 , 599 MI events ) ; the Copenhagen General Population Study ( CGPS ) , a cross-sectional general population study ( 2003 - 2006 , n = 29 388 , 994 MI events ) ; and the Copenhagen Ischemic Heart Disease Study ( CIHDS ) , a case-control study ( 1991 - 2004 , n = 2461 , 1231 MI events ) . MAIN OUTCOME MEASURES Plasma lipoprotein(a ) levels , lipoprotein(a ) kringle IV type 2 ( KIV-2 ) size polymorphism genotype , and MIs recorded from 1976 through July 2007 for all participants . RESULTS In the CCHS , multivariable-adjusted hazard ratios ( HRs ) for MI for elevated lipoprotein(a ) levels were 1.2 ( 95 % confidence interval [ CI ] , 0.9 - 1.6 ; events/10,000 person-years , 59 ) for levels between the 22nd and 66th percentile , 1.6 ( 95 % CI , 1.1 - 2.2 ; events/10,000 person-years , 75 ) for the 67th to 89th percentile , 1.9 ( 95 % CI , 1.2 - 3.0 ; events/10,000 person-years , 84 ) for the 90th to 95th percentile , and 2.6 ( 95 % CI , 1.6 - 4.1 ; events/10,000 person-years , 108 ) for levels greater than the 95th percentile , respectively , vs levels less than the 22nd percentile ( events/10,000 person-years , 55 ) ( trend P < .001 ) . Numbers of KIV-2 repeats ( sum of repeats on both alleles ) ranged from 6 to 99 and on analysis of variance explained 21 % and 27 % of all variation in plasma lipoprotein(a ) levels in the CCHS and CGPS , respectively . Mean lipoprotein(a ) levels were 56 , 31 , 20 , and 15 mg/dL for the first , second , third , and fourth quartiles of KIV-2 repeats in the CCHS , respectively ( trend P < .001 ) ; corresponding values in the CGPS were 60 , 34 , 22 , and 19 mg/dL ( trend P < .001 ) . In the CCHS , multivariable-adjusted HRs for MI were 1.5 ( 95 % CI , 1.2 - 1.9 ; events/10,000 person-years , 75 ) , 1.3 ( 95 % CI , 1.0 - 1.6 ; events/10,000 person-years , 66 ) , and 1.1 ( 95 % CI , 0.9 - 1.4 ; events/10,000 person-years , 57 ) for individuals in the first , second , and third quartiles , respectively , as compared with individuals in the fourth quartile of KIV-2 repeats ( events/10,000 person-years , 51 ) ( trend P < .001 ) . Corresponding odds ratios were 1.3 ( 95 % CI , 1.1 - 1.5 ) , 1.1 ( 95 % CI , 0.9 - 1.3 ) , and 0.9 ( 95 % CI , 0.8 - 1.1 ) in the CGPS ( trend P = .005 ) , and 1.4 ( 95 % CI , 1.1 - 1.7 ) , 1.2 ( 95 % CI , 1.0 - 1.6 ) , and 1.3 ( 95 % CI , 1.0 - 1.6 ) in the CIHDS ( trend P = .01 ) . Genetically elevated lipoprotein(a ) was associated with an HR of 1.22 ( 95 % CI , 1.09 - 1.37 ) per doubling of lipoprotein(a ) level on instrumental variable analysis , while the corresponding value for plasma lipoprotein(a ) levels on Cox regression was 1.08 ( 95 % CI , 1.03 - 1.12 ) . CONCLUSION These data are consistent with a causal association between elevated lipoprotein(a ) levels and increased risk of MI BACKGROUND To date , head-to-head trials comparing the efficacy and safety of biological disease-modifying antirheumatic drugs within the same class , including TNF inhibitors , in patients with active rheumatoid arthritis despite methotrexate therapy are lacking . We aim ed to compare the efficacy and safety of two different TNF inhibitors and to assess the efficacy and safety of switching to the other TNF inhibitor without a washout period after insufficient primary response to the first TNF inhibitor at week 12 . METHODS In this 104-week , r and omised , single-blind ( double-blind until week 12 and investigator blind thereafter ) , parallel-group , head-to-head superiority study ( EXXELERATE ) , eligible patients from 151 centres worldwide were aged 18 years or older with a diagnosis of rheumatoid arthritis at screening , as defined by the 2010 ACR/EULAR criteria , and had prognostic factors for severe disease progression , including a positive rheumatoid factor , or anti-cyclic citrullinated peptide antibody result , or both . Participants were r and omly assigned ( 1:1 ) via an interactive voice and web response system with no stratification to receive certolizumab pegol plus methotrexate or adalimumab plus methotrexate . All study staff were kept masked throughout the study and participants were masked until week 12 . At week 12 , patients were classified as responders ( by either achieving low disease activity [ LDA ] according to Disease Activity Score 28-erythrocyte sedimentation rate [ DAS28-ESR ] ≤3·2 or DAS28-ESR reduction ≥1·2 from baseline ) or as non-responders . Non-responders to the first TNF inhibitor to which they were r and omised were switched to the other TNF inhibitor with no washout period . Primary endpoints were the percentage of patients achieving a 20 % improvement according to the American College of Rheumatology criteria ( ACR20 ) at week 12 and LDA at week 104 ( week 12 non-responders were considered LDA non-responders ) . This study is registered with Clinical Trials.gov , number NCT01500278 . FINDINGS Between Dec 14 , 2011 , and Nov 11 , 2013 , 1488 patients were screened of whom 915 were r and omly assigned ; 457 to certolizumab pegol plus methotrexate and 458 to adalimumab plus methotrexate . No statistically significant difference was observed in ACR20 response at week 12 ( 314 [ 69 % ] of 454 patients and 324 [ 71 % ] of 454 patients ; odds ratio [ OR ] 0·90 [ 95 % CI 0·67 - 1·20 ] ; p=0·467 ) or DAS28-ESR LDA at week 104 ( 161 [ 35 % ] of 454 patients and 152 [ 33 % ] of 454 patients ; OR 1·09 [ 0·82 - 1·45 ] ; p=0·532 ) between certolizumab pegol plus methotrexate and adalimumab plus methotrexate , respectively . At week 12 , 65 non-responders to certolizumab pegol were switched to adalimumab and 57 non-responders to adalimumab were switched to certolizumab pegol ; 33 ( 58 % ) of 57 patients switching to certolizumab pegol and 40 ( 62 % ) of 65 patients switching to adalimumab responded 12 weeks later by achieving LDA or a DAS28-ESR reduction 1·2 or greater . 389 [ 75 % ] of 516 patients who received certolizumab pegol plus methotrexate and 386 [ 74 % ] of 523 patients who received adalimumab plus methotrexate reported treatment-emergent adverse events . Three deaths ( 1 % ) occurred in each group . No serious infection events were reported in the 70-day period after treatment switch . INTERPRETATION These results show that certolizumab pegol plus methotrexate is not superior to adalimumab plus methotrexate . The data also show the clinical benefit and safety of switching to a second TNF inhibitor without a washout period after primary failure to a first TNF inhibitor . FUNDING UCB Pharma Objectives The interleukin-6 receptor ( IL-6R ) blocker tocilizumab ( TCZ ) reduces inflammatory disease activity in rheumatoid arthritis ( RA ) but elevates lipid concentrations in some patients . We aim ed to characterise the impact of IL-6R inhibition on established and novel risk factors in active RA . Methods R and omised , multicentre , two-part , phase III trial ( 24-week double-blind , 80-week open-label ) , MEASURE , evaluated lipid and lipoprotein levels , high-density lipoprotein ( HDL ) particle composition , markers of coagulation , thrombosis and vascular function by pulse wave velocity ( PWV ) in 132 patients with RA who received TCZ or placebo . Results Median total-cholesterol , low-density lipoprotein-cholesterol ( LDL-C ) and triglyceride levels increased in TCZ versus placebo recipients by week 12 ( 12.6 % vs 1.7 % , 28.1 % vs 2.2 % , 10.6 % vs −1.9 % , respectively ; all p<0.01 ) . There were no significant differences in mean small LDL , mean oxidised LDL or total HDL-C concentrations . However , HDL-associated serum amyloid A content decreased in TCZ recipients . TCZ also induced reductions ( > 30 % ) in secretory phospholipase A2-IIA , lipoprotein(a ) , fibrinogen and D-dimers and elevation of paraoxonase ( all p<0.0001 vs placebo ) . The ApoB/ApoA1 ratio remained stable over time in both groups . PWV decreases were greater with placebo than TCZ at 12 Output:	Conclusions Despite an increase in cholesterol levels , TCZ has safe cardiovascular outcomes compared to other bDMARD
MS21971	*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: Forty-two patients with previously untreated T3/4 N1 - 4 MO/1 prostatic adenocarcinoma were treated with either cyproterone acetate ( n = 21 ; 300 mg intramuscularly per week ) or oestradiol undecylate ( n = 21 ; 100 mg intramuscularly per month ) after extensive staging which included open skeletal biopsy and pelvic lymphadenectomy in some cases . Subjective and objective parameters as well as signs of drug toxicity were recorded regularly . Evaluation after 6 months showed cyproterone acetate to be more effective in the following respects : ( 1 ) the significantly different castration effect as judged by plasma testosterone , ( 2 ) the objective voiding pattern and tumour response , with regression of palpable and histologically evaluable local tumour in 16 of 21 patients , and ( 3 ) side effects and untoward reactions . Thus cyproterone acetate is suggested as a valuable alternative in the treatment of advanced prostatic cancer 151 patients with locally advanced prostatic cancer ( T3 - 4 M0 ) , representing 38 % of the 404 cancer patients in a Finnish multicenter study , were r and omly assigned to one of three treatment arms : orchiectomy , estrogens or radiotherapy . During the 4-year follow-up period there were no significant differences in the progression rates ( appearance of metastases in bone scan ) between the therapy groups . The frequency of thromboembolic and other cardiovascular complications was highest in the estrogen group ( 13/50 patients ) . In the radiotherapy group , 19 of 45 patients had bowel or bladder complications . On the other h and , orchiectomy has few , if any , complications . The high risk of complications associated with estrogens and radiotherapy has to be taken into consideration in the selection of treatment Thirty previously untreated patients with carcinoma of the prostate were prospect ively r and omised to one of the following treatments : ethinyl oestradiol ( Etivex ) combined with polyoestradiol phosphate ( Estradurin ) ; estramustine phosphate ( Estracyt ) ; bilateral orchiectomy . Oestrogenic effects were measured by blood levels of pregnancy zone protein , sex hormone binding globulin , LH , FSH and prolactin . During a follow-up period of 6 months , estramustine phosphate and ethinyl oestradiol/polyoestradiol phosphate induced comparable changes in these proteins , suggesting comparable oestrogenic effects of these two forms of treatment in patients with prostatic carcinoma The authors made a r and omized prospect i ve study of estrogen therapy versus orchidectomy in patients with prostatic cancer ( n = 100 , Huddinge Hospital , Sweden ) to investigate the possibility of predicting cardiovascular events during hormonal treatment . Patients with preexisting cardiovascular morbidity were excluded ( 16 % ) . Prior to the allocation of therapy , the following were performed : exercise stress test ; physiologic evaluation of the peripheral circulation ; blood volume estimation ; chest x-ray ; blood tests , including hormones , lipoproteins , and antithrombin III ; and a physical examination and history by a cardiologist . Thirteen ( 25 % ) of the patients given estrogen therapy ( n = 53 ) had cardiovascular complications during the first year of treatment compared with none in the orchidectomy group . The authors made a multivariate discriminant analysis of the pretreatment examinations of the estrogen-treated patients ; this result ed in a discriminant function including S-T segment depression in lead CH2 during the exercise stress test and blood tests for cholesterol , follicle-stimulating hormone , and luteinizing hormone . This function correctly classified 84 % of the estrogen-treated patients as patients with or without risk of a cardiovascular complication . Briefly stated , if patients with prostatic cancer are examined by means of exercise stress tests and blood tests for luteinizing hormone , cholesterol , and follicle-stimulating hormone prior to treatment , the discriminant function enables the authors to identify an extremely high-risk group for cardiovascular complications if estrogen therapy is commenced . The strong association of an increased luteinizing hormone with cardiovascular complications during estrogen treatment makes it m and atory to investigate its role in the pathogenesis of atherosclerosis and cardiovascular events BACKGROUND Mortality increases after hip fractures in women and more so in men . Little is known , however , about mortality after other fractures . We investigated the mortality associated with all fracture types in elderly women and men . METHODS We did a 5-year prospect i ve cohort study in the semi-urban city of Dubbo , Australia , of all residents aged 60 years and older ( 2413 women and 1898 men ) . Low-trauma osteoporotic fractures that occurred between 1989 and 1994 , confirmed by radiography and personal interview , were classified as proximal femur , vertebral , and groupings of other major and minor fractures . We calculated st and ardised mortality rates from death certificates for people with fractures compared with the Dubbo population . FINDINGS 356 women and 137 men had low-trauma fractures . In women and men , mortality was increased in the first year after all major fractures . In women , age-st and ardised mortality ratios were 2.18 ( 95 % CI 2.03 - 2.32 ) for proximal femur , 1.66 ( 1.51 - 1.80 ) for vertebral , 1.92 ( 1.70 - 2.14 ) for other major , and 0.75 ( 0.66 - 0.84 ) for minor fractures . In men , these ratios were 3.17 ( 2.90 - 3.44 ) for proximal femur , 2.38 ( 2.17 - 2.59 ) for vertebral , 2.22 ( 1.91 - 2.52 ) for other major , and 1.45 ( 1.25 - 1.65 ) for minor fractures . There were excess deaths ( excluding minor fractures in women ) in all age-groups . INTERPRETATION All major fractures were associated with increased mortality , especially in men . The loss of potential years of life in the younger age-group shows that preventative strategies for fracture should not focus on older patients at the expense of younger women and of men BACKGROUND The present pilot study tested the clinical performance of a new pharmacokinetically guided dosing regimen of parenteral estrogen in patients with advanced prostatic carcinoma . The aim was to accelerate endocrine effects and to avoid cardiovascular side effects . METHODS Seventeen patients were r and omized to intramuscular injections of 240 mg polyestradiol phosphate ( PEP ) every second week for the first 8 weeks ( five doses ) , followed by a maintenance dose of 240 mg every month ; and 16 patients were r and omized to bilateral orchidectomy . The estrogen dosing was calculated by pharmacokinetic modelling to achieve a rapid increase in serum estradiol and thereby a fast decrease in testosterone . RESULTS The predicted increment in serum estrogen was achieved , together with a subsequent decrease in testosterone in the PEP group . In addition , there were no signs of an increased cardiovascular morbidity . This was probably due to a minimal estrogenic influence on the liver and was reflected by unchanged levels of coagulation factor VII . Clinical effects , during the first 2 years of treatment , were similar in the two treatment arms , with 12 patients in the orchidectomy group and 14 patients in the PEP group responding to treatment . CONCLUSIONS The present parenteral regimen is an efficient and time-saving estrogen regimen with a favorable side-effect profile . PEP seems to offer a potential for revival of the most cost-effective endocrine treatment of cancer of the prostate , i.e. , estrogen OBJECTIVE To evaluate the clinical efficacy and cardiovascular complications of orchidectomy or polyoestradiol phosphate ( PEP ) in the treatment of advanced prostatic cancer . PATIENTS AND METHODS In a prospect i ve , r and omized study 444 patients ( mean age 73 years , range 45 - 91 ) with T3 - 4 M0 or T1 - 4 M1 prostatic cancer were treated either by orchidectomy ( group 1 , n = 217 ) or parenteral PEP ( group 2 , n = 227 ; 240 mg/month ) . The patients were examined at 3 and 6 months after start of the therapy and thereafter every 6 months ; they were also assessed whenever they had symptoms indicating progression . Possible cardiovascular complications included myocardial infa rct ion , cerebrovascular accident , pulmonary embolism and deep vein thrombosis . RESULTS After a follow-up of 2 years there was no statistically significant difference between the groups in progression-free time ; 65 of 217 ( 30 % ) patients in group 1 showed evidence of progression , including seven ( 3 % ) who died from prostate cancer . In group 2 , 64 of 227 ( 28 % ) patients showed progression and eight ( 3.5 % ) died from prostatic cancer . There were 10 ( 5 % ) cardiovascular complications in patients in group 1 , including five ( 2 % ) cardiovascular deaths ; in group 2 there were 24 ( 11 % ) and 14 ( 6 % ) , respectively . During the first year of treatment there were three ( 1.4 % ) cardiovascular complications in group 1 and 14 ( 6 % ) in group 2 ( P < 0.05 ) , and during the second year , seven ( 4 % ) and 10 ( 6 % ) , respectively . CONCLUSION Parenteral PEP ( 240 mg/month ) seems to be as efficient as orchidectomy in inhibiting disease in patients with advanced prostatic cancer ( T3 - 4 M0 and T1 - 4 M1 ) . There were more cardiovascular complications in patients treated with PEP than after orchidectomy ; the difference was statistically significant during the first year of treatment BACKGROUND The aim of the study was to evaluate overall and prostate cancer ( PCa ) specific survival with special attention to cardiovascular ( CV ) mortality in patients primarily treated by parenteral polyestradiol phosphate ( PEP ) 240 mg/month or with orchiectomy ( OE ) , taking into account the effect of pretreatment diseases and medication , and later PCa therapies . METHODS The present Finnprostate 6 study ( 10-year follow-up ) consisted of 244 patients with locally advanced PCa ( T3 - 4 M0 ) and 200 patients with metastatic PCa ( T1 - 4 M1 ) . Patients were r and omized to OE or PEP therapy . The T3 - 4 M0 and T1 - 4 M1 patients were analyzed separately . RESULTS There was no difference in overall or PCa specific survival between the primary therapy groups in T3 - 4 M0 or T1 - 4 M1 patients . In the T3 - 4 M0 patients the primary treatment ( PEP vs. OE ) was statistically significantly associated with a risk of CV deaths ( P = 0.001 ) . Such an association was not found in the T1 - 4 M1 patients . CONCLUSIONS The primary PEP and OE therapies are equal in terms of overall and PCa specific survival in patients with T3 - 4 M0 or T1 - 4 M1 disease . In T3 - 4 M0 patients PEP increases the risk of CV deaths compared to OE but not in T1 - 4 M1 patients Thirty-eight patients with cancer of the prostate were treated with strict parenteral estrogen in the form of monthly polyestradiol phosphate injections--160 mg , 240 mg , and 320 mg -- in this nonr and omized study . In contrast to studies with oral estrogens , there have been no cardiovascular complications at a mean follow-up of 12.9 + /- 0.7 months ( SEM ) . Twenty-nine of the 38 patients ( 76 % ) have responded to therapy Objective To evaluate the cardiovascular ( CV ) complications associated with orchiectomy ( OE ) and parenteral polyestradiol phosphate ( PEP ) therapy ( 240 mg/month ) , taking into account the effect of pretreatment diseases and pretreatment medication . Material and methods A total of 244 T3–4 M0 patients and 200 T1–4 M1 patients were r and omized to either OE or PEP therapy . The two groups of patients were analyzed separately . The follow-up period was 36 months . The effect of pretreatment vascular and other diseases and pretreatment medication which may be associated with a risk of CV complications was evaluated . Results In the T3–4 M0 patients , the treatment ( PEP versus OE ) and the presence of pretreatment vascular diseases were statistically significantly associated with a risk of CV complications ( p=0.01 and 0.003 , respectively ) . In the T1–4 M1 patients , such an association was not found . No association was observed between pretreatment medication and CV complications . There was no difference in progression-free time between the therapy groups in either the T3–4 M0 or T1–4 M1 patients . Conclusion In patients with locally advanced prostatic cancer , Output:	The results provide no evidence to suggest that parenteral oestrogen , in doses sufficient to produce castrate levels of testosterone , is less effective than luteinising hormone-releasing hormone ( LHRH ) or orchidectomy in controlling prostate cancer , or that it is consistently associated with an increase in cardiovascular mortality .
MS21972	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In a recent study , children with movement clumsiness ( or Developmental Coordination Disorder-DCD ) were shown to have difficulties making rapid online corrections when reaching , demonstrated by slower and less accurate movements to double-step targets ( Hyde & Wilson , 2011 ) . These results suggest that children with DCD have difficulty using predictive estimates of limb position when making rapid adjustments to movement , in-flight . However , chronometric data alone does not provide strong evidence for this hypothesis : it remains unclear whether early ( and rapid ) control parameters or post-correction stages of the movement trajectory are affected . Thus , the overarching aim of this study was to conduct a kinematic analysis of double-step reaching in order to isolate the different control parameters that might explain the slower and less accurate double-step reaching performance of children with DCD . Participants were a new sample of 13 children with DCD aged between 8 - 12 years and 13 age-matched controls . Children were required to reach and touch one of three possible targets presented at the coordinates -20 ° , 0 ° and 20 ° on a 17 in . LCD touch-screen . For most trials ( 80 % ) the target remained stationary for the duration of movement ( non-jump trials ) , while for the remainder ( 20 % ) , the target jumped r and omly to one of two peripheral locations at movement onset ( jump trials ) . Consistent with earlier work , children with DCD were slower to initiate reaching compared to controls and showed longer MT and more errors on jump trials . Kinematic data showed that while the two groups did not differ on time to peak velocity or acceleration , children with DCD were slower to correct reach trajectory on jump trials . No group differences were observed on late kinematic markers , e.g. , post-correction time . The pattern of results support and extend earlier work showing deficits in ROC in DCD . From a computational perspective , delayed corrections to the reach trajectory suggests some difficulty integrating information about the target perturbation with a predictive ( or forward ) estimate of limb position relative to the initial target . These conclusions are discussed , along with directions for future research Children with developmental coordination disorder ( DCD ) have been demonstrated to show a deficit of inhibitory control in volitional shifts of attention . The aim of this study was to use ecological intervention to investigate the efficacy of table-tennis training on treating both problems with attentional networks and motor disorder in children with DCD . Forty-three children aged 9 - 10 years old were screened using the Movement Assessment Battery for Children and divided into DCD ( n=27 ) and typically developing ( TD , n=16 ) groups . Children with DCD were then quasi-r and omly assigned to either a DCD-training group who underwent a ten-week table-tennis training program with a frequency of 3 times a week or a DCD non-training group . Before and after training , the capacity of inhibitory control was examined with the endogenous Posner paradigm task for DCD and TD groups . Table-tennis training result ed in significant improvement of cognitive and motor functions for the children with DCD . The study demonstrated that exercise intervention employed within the school setting can benefit the inhibitory control and motor performance in children with DCD . However , future research efforts should continue to clarify whether the performance gains could be maintained over time Theoretical motor control predicts that because of delays in sensorimotor pathways , a neural system should exist in the brain that uses efferent copy of comm and s to the arm , sensory feedback , and an internal model of the dynamics of the arm to predict the future state of the h and ( i.e. , a forward model ) . We tested this theory under the hypothesis that saccadic eye movements , tracking an unseen reaching movement , would reflect the output of this state predictor . We found that in unperturbed reaching movements , saccade occurrence at any timet consistently provided an unbiased estimate of h and position at t + 196 msec . To investigate the behavior of this predictor during feedback error control , we applied 50 msec r and om-force perturbations to the moving h and . Saccades showed a sharp inhibition at 100 msec after perturbation . At ∼170 msec , there was a sharp increase in saccade probabilities . These postperturbation saccades were an unbiased estimator of h and position at saccade timet + 150 msec . The ability of the brain to guide saccades to the future position of the h and failed when a force field unexpectedly changed the dynamics of the h and immediately after perturbation . The behavior of the eyes suggested that during reaching movements , the brain computes an estimate of future h and position based on an internal model that relies on real-time proprioceptive feedback . When an error occurs in reaching movements , the estimate of future h and position is recomputed . The saccade inhibition period that follows the h and perturbation may indicate the length of time it takes for this computation to take place Children with impaired motor coordination ( or developmental coordination disorder ) have difficulty representing internally the visuospatial coordinates of intended movements . We have proposed that this deficit reflects impairment in the generation of forward models of the efference copy of intended movements―the efference-copy-deficit hypothesis . In this study , we challenged this hypothesis by examining the efficacy of an imagery intervention design ed specifically to train the forward modeling of purposive actions . A pre-post design was adopted . Fifty-four children referred with motor coordination problems were assigned r and omly to one of three groups : imagery training , traditional perceptual-motor training , and wait-list control . The imagery protocol ―delivered by an interactive CD―ROM―was shown to be equally effective to perceptual-motor training in facilitating the development of motor skill in the referred children . These results support the efference-copy-deficit hypothesis in explaining the cause of motor clumsiness in most children . Directions for future intervention studies and remediation in the field of developmental clumsiness are discussed . ( J Child Neurol 2002;17:491 - 498 ) The study investigated whether 10-week soccer training can benefit the inhibitory control and neuroelectric indices in children with developmental coordination disorder ( DCD ) . Fifty-one children were divided into groups of typically developing ( TD , n=21 ) , DCD-training ( n=16 ) , and DCD non-training ( n=14 ) individuals using the for Children test , and , before and after training , were assessed with the visuospatial attention orienting task with their lower extremities , while brain event-related potentials ( ERPs ) were concurrently recorded . The results indicated that , when compared to TD children , children with DCD responded significantly more slowly across conditions of the visuospatial attention orienting task and showed a deficit of inhibitory control capacity in their lower extremities , whereas no group differences were observed for the accuracy rate . Neuroelectric data indicated that , before training , P3 amplitude was smaller and P3 latency was slower for both DCD groups compared to TD children across conditions of the visuospatial attention orienting task ; after training , the beneficial effects were seen in the strength of inhibitory control and P3 latency in the DCD-training group . The data suggest that soccer training result ed in significant improvements in ERP and task performance indices for the children with DCD Abstract The motor control of a sequence of two motor acts forming an action was studied in the present experiment . The two analysed motor acts were reaching-grasping an object ( first target ) and placing it on a second target of the same shape and size ( experiment 1 ) . The aim was to determine whether extrinsic properties of the second target ( i.e. target distance ) could selectively influence the kinematics of reaching and grasping . Distance , position and size of both targets were r and omly varied across the experimental session . The kinematics of the initial phase of the first motor act , that is , velocity of reaching and h and shaping of grasping , were influenced by distance of the second target . No kinematic difference was found between movements executed with and without visual control of both h and and targets . These results could be due to computation of the general program of an action that takes into account extrinsic properties of the final target . Conversely , they could depend on a visual interference effect produced by the near second target on the control of the first motor act . In order to dissociate the effects due to second target distance from those due to visual interference , two control experiments were carried out . In the first control experiment ( experiment 2 ) subjects executed movements directed towards spatial locations at different distances from the first target , as in experiment 1 . However , the near second target was not presented and subjects were required to place the object on an arbitrary near position . Distance of the second ( either real or arbitrary ) target affected the reaching component of the first motor act , as in experiment 1 , but not the grasp component . In the second control experiment ( experiment 3 ) , the pure visual interference effect was tested . Subjects were required to reach and grasp the object and to lift it in either presence or absence of a second near stimulus . No effect on the initial phase of the first motor act was observed . The results of the this study suggest a dissociation in the control of reaching and grasping , concerning not only visual analysis of extrinsic properties of the immediate target but also visual analysis of the final target of the action . In other words , the notion of modularity for the motor control can be extended to the construction of an entire action & NA ; The chronometry of imagined and actual movements was investigated in a patient with a unilateral lesion of the motor cortex . Motor imagery generated highly accurate estimates of motor performance in a variety of situations , reflecting the hypokinesia of the contralesional h and . There were parallel increases in mental and actual movement times from proximal to distal limb segments . Bimanual movements adopted the slower speed of the impaired h and in both conditions . Imagined motor sequences to the beat of a metronome predicted the maximum speed reached in actual performance . Finally , visually guided pointing showed the same target‐size effects in the imagery and movement conditions . The results are in agreement with the hypothesis that common cerebral motor representations are activated when imaging and planning voluntary movements The aims of this study were to determine the motor outcome of extremely‐low‐birthweight ( ELBW ; < 1000 g ) or very preterm ( < 28wks ) children compared with normal birthweight ( NBW ) children , to establish the perinatal associations of developmental coordination disorder ( DCD ) and its cognitive and behavioural consequences . Participants were consecutive surviving ELBW or very preterm children and r and omly selected NBW(>2499 g ) children born in the state of Victoria , Australia , in 1991 or 1992 . Main outcomes were : ( 1 ) results of the Movement Assessment Battery for Children ( MABC ) at 8 years of age ; ( 2 ) cognitive function ; ( 3 ) academic progress ; and ( 4 ) behaviour . Of 298 consecutive ELBW/very preterm survivors , 255 ( 85.6 % ; 117 males , 138 females ) had the MABC at a mean age of 8 years 8 months . More ELBW/very preterm children ( 9.5 % ) had DCD than the NBW group ( 2 % , p=0.001 ) . Only male sex increased the likelihood of DCD in ELBW/very preterm children ( p=0.017 ) . ELBW/very preterm children with DCD had worse cognitive function and academic test scores ( up to 1SD below those without DCD ) ; they also had more adaptive behaviour and externalizing problems , but not internalizing problems . DCD is more common in ELBW/very preterm children , has few perinatal correlates , and is associated with poor cognitive and academic performance as well as increased behaviour problems The purpose of the study was to examine the relationship between the extremities in different aspects of motor performance , including simple reaction time , choice reaction time , speed of movement , tapping speed , and coordination , i.e. , speed of movement/accuracy . 186 healthy r and omly selected right-h and ed subjects ( 93 men , 93 women ; aged 21–70 years ) were measured on a test battery of five tests for both h and s and feet . Correlations between the extremities in motor performance were highest between h and s ( r = .71–.80 , p<.001 ) or between feet ( r = .57–.88 , p<.001 ) depending on the complexity of response for all subjects . These relations remained at almost the same magnitude even when age was eliminated . Correlations between the upper and lower extremities were lower ( r = .40–.62 ) . Correlations between extremities were lower for one age group ( 21–30 years ) than for all subjects ( 21–70 years ) . These results showed that the motor performance for the h and s is not a very good indicator of the motor performance of the lower extremities , especially in a homogeneous age group , and it seems that the lower extremities should be studied with specific motor performance tests Consistent preferences for particular types of movement suggest criteria for movement selection . These can be important when , as is usually the case , infinitely many movements allow a task to be achieved . The experiments reported here were design ed to identify the source of a strong preference observed in earlier object-manipulation studies . In those earlier studies , subjects usually grabbed objects to be moved from one location to another in a way that afforded a comfortable final posture rather than a comfortable initial posture ( the end-state comfort effect ) . The comfortable final state usually allowed the forearm to be at or near the middle of its range of motion on the pronation-supination dimension . The hypothesis tested here was that the end-state comfort effect stemmed from an expectation that movements can be made more quickly in the middle of the pronation-supination range than at either extreme . To test this hypothesis , we asked subjects , in the first experiment , to perform a h and le rotation task that dem and ed little or no precision and so no need to make rapid to- and -fro homing-in movements near the end of the rotation . Half the subjects did not show the end-state comfort effect , in contrast to all previous studies , where all subjects showed the effect . An incidental finding of the first experiment was that h and le rotations that ended at or near the end of the range of motion took longer than h and le rotations that ended at or near the middle of the range of motion . To test the latter result more carefully , we asked subjects , in Experiments 2 and 3 , to oscillate the forearm as quickly as possible , either in the supination part of the forearm rotation range , in the middle part of the range , or in the pronation part of the range . As predicted , oscillation frequencies were highest in midrange , and this was true for both h and s. The results as a whole have implication Output:	Results showed compromised control of overt and covert eye movements , dynamic postural control , manual control for tasks that vary in complexity , and for motor imagery of manual and whole-body postures . Importantly , this review shows support for general hypothesis that deficits of predictive control manifest in DCD across effector systems
MS21973	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE To evaluate the safety and efficacy of intravenous ( IV ) sodium ferric gluconate complex ( FG ) , oral ferrous sulfate , or no iron to increase hemoglobin ( Hb ) in anemic cancer patients receiving chemotherapy and epoetin alfa . PATIENTS AND METHODS In this open-label , multicenter trial , 187 patients with chemotherapy-related anemia ( Hb < 11 g/dl ; serum ferritin > or = 100 ng/ml or transferrin saturation > or = 15 % ) scheduled to receive chemotherapy and epoetin alfa ( 40,000 U subcutaneously weekly ) were r and omized to 8 weeks of 125 mg of IV FG weekly , 325 mg of oral ferrous sulfate three times daily , or no iron . The primary outcome was a change in Hb from baseline to endpoint , first whole-blood or red blood cell transfusion , or study withdrawal . RESULTS One hundred twenty-nine patients were evaluable for efficacy ( FG , n = 41 ; oral iron , n = 44 ; no iron , n = 44 ) . Mean increase in Hb was 2.4 g/dl ( 95 % confidence interval [ CI ] , 2.1 - 2.7 ) for FG ( p = .0092 vs. oral iron ; p = .0044 vs. no iron ) , 1.6 g/dl ( 95 % CI , 1.1 - 2.1 ) for oral iron ( p = .7695 vs. no iron ) , and 1.5 g/dl ( 95 % CI , 1.1 - 1.9 ) for no iron . Hb response ( increase > or = 2 g/dl ) was 73 % for FG ( p = .0099 vs. oral iron ; p = .0029 vs. no iron ) , 46 % for oral iron ( p = .6687 vs. no iron ) , and 41 % for no iron . FG was well tolerated . CONCLUSION For cancer patients with chemotherapy-related anemia receiving epoetin alfa , FG produces a significantly greater increase in Hb and Hb response compared with oral iron or no iron , supporting more aggressive treatment with IV iron supplementation for these patients BACKGROUND : It is uncertain whether anemia in elderly patients after primary hip arthroplasty has an effect on their quality of life . METHODS : We conducted a prospect i ve observational study over 3 mo to investigate the association between discharge hemoglobin levels and subjective experience of quality of life at 2 mo postoperatively in patients aged over 65 yr who were scheduled for primary hip arthroplasty . Quality of life was measured preoperatively and at 2 mo postoperatively using the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) and the Functional Assessment of Cancer Therapy Anemia ( FACT-Anemia ) subscale . Pearson correlation coefficients between change in SF-36 and FACT-Anemia subscale scores ( from preoperatively to 2 mo postoperatively ) and hemoglobin on Day 8 were calculated . RESULTS : Eighty-seven patients were included in the study . Data were available at 2 mo postoperatively from 79 of these patients . The correlation between Day 8 postoperative hemoglobin and change in SF-36 was 0.49 ( P < 0.0005 ) and change in FACT-Anemia subscale score was 0.46 ( P = < 0.0005 ) . The correlation was not significantly changed after adjusting for advancing age , presence of significant cardiovascular disease , or whether the patient was transfused . CONCLUSIONS : We found a positive correlation between hemoglobin levels on discharge and change in quality of life scores from preoperatively to 2 mo postoperatively in patients over 65 yr old after primary hip arthroplasty BACKGROUND AND OBJECTIVES Patients undergoing surgery for hip fracture ( HF ) often receive perioperative allogeneic blood transfusions ( ABT ) to avoid anaemia . However , concerns about the adverse effects of ABT have prompted the review of transfusion practice and the search for a safer treatment of perioperative anaemia . MATERIAL S AND METHODS We prospect ively investigated the effect of a blood-saving protocol of perioperative iron sucrose ( 3 x 200 mg/48 h , intravenously ) plus erythropoietin ( 1 x 40,000 IU , subcutaneously ) if admission haemoglobin level < 130 g/l , on transfusion requirements and postoperative morbid-mortality in patients with HF ( group 2 ; n= 83 ) . A parallel series of 41 HF patients admitted to another surgical unit within the same hospital served as the control group ( group 1 ) . Perioperative blood sample s were taken for haematimetric , iron metabolism and inflammatory parameter determination . RESULTS This blood-saving protocol reduced the number of transfused patients ( P < 0.001 ) , the number of transfused units ( P < 0.0001 ) , increased the reticulocyte count and improved iron metabolism . In addition , the blood-saving protocol also reduced the rate of postoperative infections ( P = 0.016 ) , but not the 30-day mortality rate or the mean length of hospital stay . CONCLUSIONS The blood-saving protocol implemented seems to reduce ABT requirements in patients with HF , and is associated with a lower postoperative morbidity . The possible mechanisms involved in these effects are discussed BACKGROUND Unilateral total knee replacement ( TKR ) can result in a substantial blood loss and 30 - 50 % of these patients receive allogeneic blood transfusion ( ABT ) , this transfusion rate may be even higher among anaemic patients . PATIENTS AND METHODS We assessed the requirements for ABT in 156 consecutive patients undergoing surgery for primary TKR , who received iron ferrous sulphate ( 256 mg/day ; 80 mg of Fe(2 + ) ) , vitamin C ( 1000 mg/day ) and folic acid ( 5mg/day ) during the 30 - 45 days preceding surgery , and who were transfused if Hb < 80 g/L and /or clinical signs/symptoms of acute anaemia/hypoxemia ( Group 2 ) . A previous series of 156 TKR patients serves as a control group ( Group 1 ) . RESULTS Compared to those in Group 1 , patients in Group 2 presented a lower transfusion rate ( 5.8 % vs. 32 % , for Group 2 and Group 1 , respectively ; p<0.01 ) , and a lower transfusion index ( 1.78+/-0.44 vs. 2.22+/-0.65 units per transfused patient , respectively ; p<0.05 ) . After patient 's stratification according to a preoperative Hb above or below 130 g/L , the differences in transfusion rate remained significant , although 19 % of patients from Group 2 still needed ABT if their preoperative Hb < 130 g/L. CONCLUSION This protocol seems to be effective for avoiding ABT in non-anaemic TKR patients , whereas for anaemic patients another blood saving strategy , such us preoperative erythropoietin administration or postoperative blood salvage , should be added to further increase its effectiveness Objective : To determine the effect of admission hemoglobin level on patient outcome after hip fracture . Study Design : Prospect i ve , consecutive . Patients : From July 1991 to June 1997 , 395 communitydwelling patients sixty‐five years of age or older who had sustained an operatively treated femoral neck or intertrochanteric fracture were prospect ively followed up . Main Outcome Measurements : Postoperative complications , in‐hospital mortality rate , hospital length of stay , hospital discharge status , place of residence at one year , and mortality and recovery of ambulatory ability and activities of daily living status at three , six , and twelve months . Results : Women with admission hemoglobin levels below 12.0 grams per deciliter and men with admission hemoglobin levels below 13.0 grams per deciliter were classified as anemic . One hundred eighty patients ( 45.6 percent ) were considered anemic on admission . Patients who were anemic were more likely to have an American Society of Anesthesiologists rating of III or IV and have sustained an intertrochanteric fracture . Hospital length of stay and mortality rate at six and twelve months were significantly higher for patients who were anemic on admission . There were no differences in the incidence of postoperative complications , hospital discharge status , place of residence at one year , in‐hospital mortality rate , and three‐month mortality rate between patients who were and were not anemic on admission . In addition , there were no differences in the recovery of ambulatory ability and of basic and instrumental activities of daily living status at three , six , and twelve months between the two patient groups . Conclusions : Patients at risk for poor outcomes after hip fracture can be identified by assessing hemoglobin levels at hospital admission Background Total hip replacement ( THR ) is associated with a significant perioperative blood loss , and 30–50 % of these patients receive allogeneic blood transfusion ( ABT ) . We evaluated the clinical utility of washed shed blood ( WSB ) return to reduce ABT in THR patients . Study design and methods Data from 108 consecutive THR patients were prospect ively collected . WSB salvage and reinfusion ( OrthoPAT ) was intended for 60 ( Reinfusion group ) , whereas the remaining 48 patients served as control group . Patients received ABT if haemoglobin < 8 g/dl or clinical signs and symptoms of acute anemia . Results WSB return was possible in 49 patients ( 205 ± 151 ml of erythrocyte/patient ) , without any clinical ly relevant incident . Return of WSB decreased both the ABT rate ( 48 vs. 15 % , for control and reinfusion groups , respectively ; P = 0.001 ) and the ABT index ( 371 ± 154 ml RBC vs. 53 ± 117 ml RBC , respectively ; P = 0.001 ) , without differences between cemented and uncemented THR . In addition , patients from reinfusion group showed a trend to lower postoperative infection rate ( 10 vs. 2 % , respectively ; P = 0.086 ) . Conclusions Perioperative salvage and return of WSB in THR seems to effectively reduce the requirements for ABT . However , for patients with preoperative Hb < 13 g/dl , some additional blood saving method should be associated to WSB return Patients undergoing total knee arthroplasty ( TKA ) are at high risk for postoperative anemia and allogeneic blood transfusions . Risks associated with allogeneic blood exposure ( ie , infection , fluid overload , and longer hospital stays ) have prompted alternative blood management strategies . The main goal of this study was to evaluate whether a single change in the clinical blood management of patients undergoing TKA reduced the severity of postoperative anemia or the need for allogeneic blood transfusions . A second goal of this study was to assess the financial impact of the change on the institution . This study compared perioperative cell salvage , preoperative autologous blood donation , and the practice of using allogeneic blood alone in patients undergoing TKA . Clinical and financial data of 154 unique cases of primary TKA at the Mayo Clinic Arizona were retrospectively review ed . Transfusion rates were 25 % , 18 % , and 52 % respectively for patients in the cell salvage , preoperative autologous blood donation , and allogeneic blood only groups . Respective relative risk reductions were 51.9 % ( P=.007 ) and 65.4 % ( P=.002 ) with the use of cell salvage or preoperative autologous blood donation versus allogeneic alone . Cell salvage and preoperative autologous blood donation were found to significantly reduce the requirements for allogeneic blood transfusions ; these techniques were found to be roughly equivalent in clinical benefit when compared to the use of allogeneic blood alone . The logistical advantages of cell salvage ( ie , no preoperative blood donation , no risk of wasting blood units ) were associated with greater costs to the institution OBJECTIVES To assess the risk of postoperative infection associated with blood transfusion in patients who undergo primary total hip arthroplasty . DESIGN A retrospective cohort study . SETTING Victoria General Hospital , Halifax , ( a tertiary-care centre ) . PATIENTS All patients who underwent primary total hip replacement between 1990 and 1995 ( N = 1206 ) . INTERVENTIONS Hip replacement with or without perioperative blood transfusion . OUTCOME MEASURES The rate of postoperative infection , the number of blood transfusions , patient age and sex , duration of surgery and the surgeon who performed the procedure . Victoria General Hospital medical records , the transfusion services record and the Dalhousie University Hip Study data bases were integrated and analyzed using a st and ard statistical package . RESULTS The incidence of infection postoperative was 9.9 % overall , 8.4 % in patients receiving no transfusion , and 14 % in those receiving homologous transfusion ( p = 0.035 ) . There were no infections in the 11 patients who received an autologous blood transfusion . Significant predictors of postoperative infection were sex , age and duration surgery ; these were not confounding variables multivariate analysis ) . Neither the operating surgeon nor the blood product transfused affected the infection rate . CONCLUSIONS These findings suggest an Output:	Treatment of preoperative anemia with iron , with or without erythropoietin , and perioperative cell salvage decreased the need for blood transfusion and may contribute to improved patient outcomes .
MS21974	*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 Midtrimester amniocentesis to investigate fetal karyotype carries a small risk of fetal loss . AIM To test the hypothesis that progesterone prophylaxis may reduce this . STUDY DESIGN A r and omised controlled trial comparing a short prophylactic treatment with progesterone after amniocentesis with untreated controls . RESULTS There were no differences in frequency of miscarriage , preterm delivery or neonatal outcome . CONCLUSION Prophylactic progesterone treatment after amniocentesis does not improve obstetric outcome A prior report suggested that active-duty pregnant women are at increased risk for low-birth weight infants and a higher perinatal mortality rate . The present double-blind investigation was design ed to prospect ively evaluate that risk and to test the efficacy of 17 alpha-hydroxyprogesterone caproate to prevent reported complications . Three groups of active-duty women were studied , beginning between 16 and 20 weeks ' gestation . They were similar for parity , previous abortion , race , cigarette smoking , and marital status . Of these , 80 were given 17 alpha-hydroxyprogesterone caproate , 88 received placebo , and 78 declined to participate in the protocol . There was no significant differences in the three groups when comparisons were made for low-birth weight infants and for perinatal mortality . However , when comparison was made to a military dependent population , they had a significantly worse outcome with regard to both perinatal mortality ( p = 0.001 ) and infants with a birth weight less than 2,500 gm ( p = 0.01 ) . We concluded that pregnant military personnel were at increased risk for adverse pregnancy outcome , but that this risk was not altered by therapy with 17 alpha-hydroxyprogesterone caproate OBJECTIVE The purpose of this study was to evaluate the effect of prophylactic vaginal progesterone in decreasing preterm birth rate in a high-risk population . STUDY DESIGN A r and omized , double-blind , placebo-controlled study included 142 high-risk singleton pregnancies . Progesterone ( 100 mg ) or placebo was administered daily by vaginal suppository and all patients underwent uterine contraction monitoring with an external tocodynamometer once a week for 60 minutes , between 24 and 34 weeks of gestation . Progesterone ( n = 72 ) and placebo ( n = 70 ) groups were compared for epidemiologic characteristics , uterine contraction frequency , and incidence of preterm birth . Data were compared by chi(2 ) analysis and Fisher exact test . RESULTS The preterm birth rate was 21.1 % ( 30/142 ) . Differences in uterine activity were found between the progesterone and placebo groups ( 23.6 % vs 54.3 % , respectively ; P < .05 ) and in preterm birth between progesterone and placebo ( 13.8 % vs 28.5 % , respectively ; P < .05 ) . More women were delivered before 34 weeks in the placebo group ( 18.5 % ) than in the progesterone group ( 2.7 % ) ( P < .05 ) . CONCLUSION Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity Patients with multiple gestations or recalcitrant preterm labor are at very high risk for preterm birth in spite of adequate tocolysis . Subcutaneous infusion of tocolytic medications on an ambulatory basis has been used in several small series and has effectively prolonged gestation . This retrospective analysis presents data from 992 patients at very high risk for preterm delivery who were prescribed this therapy . The amount of tocolytic medication was individualized by utilizing the patient 's volume of distribution and clearance . Pharmacists adjusted the dosage based on uterine activity strips received by nursing personnel . The average basal rate was .073 + /- .020 mg/h . Patients received an average of seven scheduled boluses per day and 1.54 + /- .93 unscheduled boluses per week ( .25 + /- .03 mg each ) . The therapy extended the gestation a mean of 38 + /- 23 days and average gestational age at delivery was 36.3 + /- 2.6 weeks with a mean birthweight of 2759 + /- 681 g. This study , utilizing a large number of patients , confirms earlier reports that for women at very high risk for preterm delivery subcutaneous tocolytic infusion therapy is beneficial . Prospect i ve studies evaluating such treatment on a r and omized basis are indicated The potential tocolytic effect of natural progesterone administration on premature labor was investigated in a double-blind study . An oral progesterone formulation was used because its ability to increase both plasma and myometrial concentration of progesterone in pregnant women had been previously demonstrated . Furthermore , no commercial intravenous or intramuscular natural progesterone formulation is currently available in France . Fifty-seven patients in two obstetric clinics , admitted because of the risk of premature delivery , were included in the study , and uterine contractility and fetal cardiac rhythm were monitored in all of them . At r and om and after 30 minutes ' rest , 29 women absorbed four capsules of 100 mg of progesterone each and 28 women absorbed four capsules of a placebo . Plasma progesterone levels were evaluated in all cases after 30 minutes ' rest and 1 hour after absorption of the capsules . The results showed that bed rest and placebo administration decrease uterine activity in 42 % of the cases and oral progesterone decreases activity in 75 % to 88 % of cases , depending on the initial severity of the menace of premature delivery . The difference between the effects of progesterone and of placebo is significant . The tocolytic effect of oral progesterone is not as intense or as rapid as the effect of intravenous beta-mimetics but is sufficient in 80 % of cases , on the average , to stop the premature labor without any detectable side effects . This tocolytic effect of oral progesterone is related not just to an increase in plasma progesterone levels but probably to an increase in myometrial progesterone concentration There are indications that prophylactic administration of 17α-hydroxyprogesterone caproate ( 17α-OHP-C ) could be beneficial in the treatment of women at risk for preterm delivery . Since twin pregnancy is commonly associated with prematurity , 77 women with twin pregnancy were treated during the last trimester until the 37th gestational week with weekly injections of either 17α-OHP-C or a placebo , following double-blind principles . The gestational length and birth weight and the outcome of the neonates were similar in both groups . The administration of 17α-OHP-C thus seems ineffective in the prevention of prematurity risks associated with twin pregnancy . ( Obstet Gynecol 56:692 , 1980 The results of a study concerning the treatment of acute menace of preterm labor are given : beta-mimetics were administered intravenously in all cases ( 44 ) and micronized progesterone or placebo was administered orally after classical double-blind r and omization ( 22 cases in each group ) . The mean index of pregnancy prolongation was the same in both groups . However the mean duration of the intravenous perfusion and the mean quantity of beta-mimetics administered intravenously were significantly reduced in the progesterone group ( P less than 0.01 ) . The mean duration of hospital stay was also significantly reduced ( P less than 0.05 ) . Cost and risks are finally significantly lessened Output:	No differences in rates of hospital admissions for threatened preterm labor or perinatal mortality were noted for subjects receiving progestational agents in general or for those receiving only 17α-hydroxyprogesterone caproate specifically . : The use of progestational agents and 17α-hydroxyprogesterone caproate reduced the incidence of preterm birth and low birth weight newborns
MS21975	*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 Human re source limitations are a challenge to the delivery of antiretroviral therapy ( ART ) in low-re source setting s. We conducted a cluster r and omized trial to assess the effect of community-based peer health workers ( PHW ) on AIDS care of adults in Rakai , Ug and a. Methodology /Principal Findings 15 AIDS clinics were r and omized 2∶1 to receive the PHW intervention ( n = 10 ) or control ( n = 5 ) . PHW tasks included clinic and home-based provision of counseling , clinical , adherence to ART , and social support . Primary outcomes were adherence and cumulative risk of virologic failure ( > 400 copies/mL ) . Secondary outcomes were virologic failure at each 24 week time point up to 192 weeks of ART . Analysis was by intention to treat . From May 2006 to July 2008 , 1336 patients were followed . 444 ( 33 % ) of these patients were already on ART at the start of the study . No significant differences were found in lack of adherence ( < 95 % pill count adherence risk ratio [ RR ] 0.55 , 95 % confidence interval [ CI ] 0.23–1.35 ; < 100 % adherence RR 1.10 , 95 % CI 0.94–1.30 ) , cumulative risk of virologic failure ( RR 0.81 , 95 % CI 0.61–1.08 ) or in shorter-term virologic outcomes ( 24 week virologic failure RR 0.93 , 95 % CI 0.65–1.32 ; 48 week , RR 0.83 , 95 % CI 0.47–1.48 ; 72 week , RR 0.81 , 95 % CI 0.44–1.49 ) . However , virologic failure rates ≥96 weeks into ART were significantly decreased in the intervention arm compared to the control arm ( 96 week failure RR 0.50 , 95 % CI 0.31–0.81 ; 120 week , RR 0.59 , 95 % CI 0.22–1.60 ; 144 week , RR 0.39 , 95 % CI 0.16–0.95 ; 168 week , RR 0.30 , 95 % CI 0.097–0.92 ; 192 week , RR 0.067 , 95 % CI 0.0065–0.71 ) . Conclusions / Significance A PHW intervention was associated with decreased virologic failure rates occurring 96 weeks and longer into ART , but did not affect cumulative risk of virologic failure , adherence measures , or shorter-term virologic outcomes . PHWs may be an effective intervention to sustain long-term ART in low-re source setting s. Trial Registration Clinical Trials.gov Background Prevention of mother to child HIV transmission ( PMTCT ) programmes have great potential to achieve virtual elimination of perinatal HIV transmission provided that PMTCT recommendations are properly followed . This study assessed mothers and infants adherence to medication regimen for PMTCT and the proportions of exposed infants who were followed up in the PMTCT programme . Methods A prospect i ve cohort study was conducted among 282 HIV-positive mothers attending 15 health facilities in Addis Ababa , Ethiopia . Descriptive statistics , bivariate and mulitivariate logistic regression analyses were done . Results Of 282 mothers enrolled in the cohort , 232 ( 82 % , 95 % CI 77 - 86 % ) initiated medication during pregnancy , 154 ( 64 % ) initiated combined zidovudine ( ZDV ) prophylaxis regimen while 78 ( 33 % ) were initiated lifelong antiretroviral treatment ( ART ) . In total , 171 ( 60 % , 95 % CI 55 - 66 % ) mothers ingested medication during labour . Of the 221 live born infants ( including two sets of twins ) , 191 ( 87 % , 95 % CI 81 - 90 % ) ingested ZDV and single-dose nevirapine ( sdNVP ) at birth . Of the 219 live births ( twin births were counted once ) , 148 ( 68 % , 95 % CI 61 - 73 % ) mother-infant pairs ingested their medication at birth . Medication ingested by mother-infant pairs at birth was significantly and independently associated with place of delivery . Mother-infant pairs attended in health facilities at birth were more likely ( OR 6.7 95 % CI 2.90 - 21.65 ) to ingest their medication than those who were attended at home . Overall , 189 ( 86 % , 95 % CI 80 - 90 % ) infants were brought for first pentavalent vaccine and 115 ( 52 % , 95 % CI 45 - 58 % ) for early infant diagnosis at six-weeks postpartum . Among the infants brought for early diagnosis , 71 ( 32 % , 95 % CI 26 - 39 % ) had documented HIV test results and six ( 8.4 % ) were HIV positive . Conclusions We found a progressive decline in medication adherence across the perinatal period . There is a big gap between mediation initiated during pregnancy and actually ingested by the mother-infant pairs at birth . Follow up for HIV-exposed infants seem not to be organized and is inconsistent . In order to maximize effectiveness of the PMTCT programme , the rate of institutional delivery should be increased , the quality of obstetric services should be improved and missed opportunities to exposed infant follow up should be minimized Background The aim of this study was to describe barriers to accessing and accepting highly active antiretroviral therapy ( HAART ) by HIV-positive mothers in the Ug and an Kabarole District 's Programme for the Prevention of Mother to Child Transmission-Plus ( PMTCT-Plus ) . Methods Our study was a qualitative descriptive exploratory study using thematic analysis . Individual in-depth interviews ( n = 45 ) were conducted with r and omly selected HIV-positive mothers who attended this programme , and who : ( a ) never enrolled in HAART ( n = 17 ) ; ( b ) enrolled but did not come back to receive HAART ( n = 2 ) ; ( c ) defaulted/interrupted HAART ( n = 14 ) ; and ( d ) are currently adhering to HAART ( n = 12 ) . A focus group was also conducted to verify the results from the interviews . Results Results indicated that economic concerns , particularly transport costs from residences to the clinics , represented the greatest barrier to accessing treatment . In addition , HIV-related stigma and non-disclosure of HIV status to clients ' sexual partners , long waiting times at the clinic and suboptimal provider-patient interactions at the hospital emerged as significant barriers . Conclusions These barriers to antiretroviral treatment of pregnant and post-natal women need to be addressed in order to improve HAART uptake and adherence for this group of the population . This would improve their survival and , at the same time , drastically reduce HIV transmission from mother to child Background Global coverage of prevention of mother-to-child ( PMTCT ) services reached 53 % in 2009 . However the number of pregnant women who test positive for HIV in antenatal clinics and who link into long-term HIV care is not known in many re source -poor countries . We measured the proportion of HIV-positive pregnant women in Mwanza city , Tanzania , who completed the cascade of care from antenatal HIV diagnosis to assessment and engagement in care in adult HIV clinics . Methods Thirty antenatal and maternity ward health workers were interviewed about PMTCT activities . Nine antenatal HIV education sessions were observed . A prospect i ve cohort of 403 HIV-positive women was enrolled by specially-trained clinicians and nurses on admission to delivery and followed for four months post-partum . Information was collected on referral and attendance at adult HIV clinics , eligibility for highly active antiretroviral therapy ( HAART ) and reasons for lack of attendance . Results Overall , 70 % of PMTCT health workers referred HIV-positive pregnant women to the HIV clinic for assessment and care . Antenatal HIV education sessions did not cover on-going care for HIV-infected women . Of 310 cohort participants tested in pregnancy , 51 % had received an HIV clinic referral pre-delivery . Only 32 % of 244 women followed to four months post-partum had attended an HIV clinic and been assessed for HAART eligibility . Non-attendance for HIV care was independently associated with fewer antenatal visits , poor PMTCT prophylaxis compliance , non-disclosure of HIV status , and non-Sukuma ethnicity . Conclusion Most women identified as HIV-positive during pregnancy were not assessed for HAART eligibility during pregnancy or in the first four months post-partum . Initiating HAART at the antenatal clinic , improved counselling and linkages to care between PMTCT and adult HIV treatment services and reducing stigma surrounding disclosure of HIV results would benefit on-going care of HIV-positive pregnant women Objective : There is limited evidence on whether growing mobile phone availability in sub-Saharan Africa can be used to promote high adherence to antiretroviral therapy ( ART ) . This study tested the efficacy of short message service ( SMS ) reminders on adherence to ART among patients attending a rural clinic in Kenya . Design : A r and omized controlled trial of four SMS reminder interventions with 48 weeks of follow-up . Methods : Four hundred and thirty-one adult patients who had initiated ART within 3 months were enrolled and r and omly assigned to a control group or one of the four intervention groups . Participants in the intervention groups received SMS reminders that were either short or long and sent at a daily or weekly frequency . Adherence was measured using the medication event monitoring system . The primary outcome was whether adherence exceeded 90 % during each 12-week period of analysis and the 48-week study period . The secondary outcome was whether there were treatment interruptions lasting at least 48 h. Results : In intention-to-treat analysis , 53 % of participants receiving weekly SMS reminders achieved adherence of at least 90 % during the 48 weeks of the study , compared with 40 % of participants in the control group ( P = 0.03 ) . Participants in groups receiving weekly reminders were also significantly less likely to experience treatment interruptions exceeding 48 h during the 48-week follow-up period than participants in the control group ( 81 vs. 90 % , P = 0.03 ) . Conclusion : These results suggest that SMS reminders may be an important tool to achieve optimal treatment response in re source -limited setting Objective : To compare compliance and infant HIV-1 infection risk at 6 weeks with the Thai-CDC and HIVNET-012 antiretroviral regimens in a field setting . Design : R and omized clinical trial . Setting : Tertiary hospital antenatal clinic in Nairobi , Kenya . Participants : HIV-1 infected women referred from primary care clinics . Interventions : Thai-CDC zidovudine regimen or HIVNET-012 nevirapine regimen . Main outcome measures : Women were considered compliant if they used ⩾ 80 % of the doses . Infants were tested for HIV-1 at 6 weeks . Results : Seventy women were r and omized to Thai-CDC and 69 to HIVNET-012 regimens . More women were compliant with the antenatal ( 86 % ) than the intrapartum ( 44 % ) Thai-CDC regimen doses ( P = 0.001 ) . Ninety-seven per cent took the maternal and 91 % gave the infant dose of the HIVNET-012 regimen ( P = 0.2 ) . Overall , 41 % were compliant with the Thai-CDC regimen and 87 % with the HIVNET-012 regimen ( P < 0.001 ) . Compliance with the Thai-CDC regimen was associated with partner support of antiretroviral use [ odds ratio ( OR ) , 3.0 ; , 95 % confidence interval ( CI ) , 1.0–9.1 ] and knowledge at recruitment that antiretroviral drugs could prevent infant HIV-1 ( OR , 2.9 ; 95 % CI , 1.0–8.1 ) . Compliance with the HIVNET-012 regimen was associated with partner notification ( OR , 8.0 ; 95 % CI , 1.5–50 ) and partner willingness to have HIV-1 testing ( OR , 7.5 ; 95 % CI , 1.4–40 ) . There was a trend for a higher risk of transmission with the HIVNET-012 regimen than with the Thai-CDC regimen ( 22 % versus 9 % ; P = 0.07 ) . Conclusion : Compliance with the Thai-CDC and HIVNET-012 regimens was comparable to that in efficacy trials . Partner involvement , support and education on perinatal HIV-1 prevention may improve compliance and increase the number of infants protected from HIV-1 infection Universal nevirapine ( NVP ) therapy ( provision of the drug without HIV testing ) has been suggested as potentially superior to targeted NVP therapy ( provision of the drug to seropositive patients identified through voluntary Output:	Stigma and fear of status disclosure to partners , family or community members ( community-level factors ) were the most frequently cited barriers overall and across time . The extent of partner/community support was another major factor impeding or facilitating the uptake of PMTCT ARVs , while cultural traditions including preferences for traditional healers and birth attendants were also common . Key health-systems issues included poor staff-client interactions , staff shortages , service accessibility and non-facility deliveries .
MS21976	*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 Whether there is an association between depression at the time of acute myocardial infa rct ion and subsequent risk of cardiac complications and death remains controversial . Most studies of this risk factor have been limited to patients of single institutions , and this might account for the varying results . We prospect ively evaluated patients admitted to 5 tertiary care and 5 community hospitals and followed them for 1 year to measure the prevalence and prognostic impact of depressive symptoms after acute myocardial infa rct ion . METHODS Patients were recruited for the study by trained nurse interviewers who had documented acute myocardial infa rct ion within 2 - 3 days of admission . The nurses collected information from the medical records and asked study subjects to complete the Beck Depression Inventory question naire during their stay in hospital and using a mailed question naire 30 days , 6 months and 1 year later . We obtained information on vital status for patients lost to follow-up from a central death registry . RESULTS Of the 587 study subjects , 550 ( 94 % ) completed the Beck Depression Inventory at baseline and 191 ( 35 % ) had a score of 10 or more , indicating at least mild depression . Rates of depression did not vary over the follow-up period and were similar among patients admitted to tertiary care or community hospitals . Depressed patients were more likely to undergo catheterization ( 57 % v. 47 % , 95 % confidence interval [ CI ] around the difference 0.1%-19.6 % ) and were more likely to undergo percutaneous coronary intervention ( 32 % v. 24 % , 95 % CI around the difference 0.1%-16.2 % ) within 30 days of first admission to hospital . Patients with depression on admission had higher rates of a composite of cardiac complications , including recurrent ischemia , infa rct ion or congestive heart failure during their first stay in hospital or readmission for angina , recurrent acute myocardial infa rct ion , congestive heart failure or arrhythmia ( adjusted hazard ratio 1.4 , 95 % CI 1.05 - 1.86 ) , compared with patients who were not depressed on admission . After 1 year , death rates were higher among patients who were depressed at admission ( 30 patients , 16 % ) compared with nondepressed patients ( 28 patients , 8 % ) , although the difference was not statistically significant ( hazard ratio 1.3 , 95 % CI 0.59 - 3.05 ) . INTERPRETATION Depressive symptoms are common after acute myocardial infa rct ion and are associated with a slight increase in risk of in-hospital catheterization and angiography and readmission because of cardiac complications . Death was infrequent , with no statistically significant difference between the 2 groups Plasma cortisol and platelet serotonin ( 5-hydroxytryptamine , 5-HT ) concentrations were determined in 39 male psychotic and 39 male non-psychotic depressed in patients , and in 69 male healthy control subjects . Psychotic or non-psychotic depressed patients had higher predexamethasone plasma cortisol levels than found in the control group . After the dexamethasone suppression test ( DST ) , psychotic and non-psychotic depressed patients were subdivided into suppressors and non-suppressors . Psychotic and non-psychotic patients had significantly different platelet 5-HT concentrations among themselves and compared with the control group . However , there was no significant correlation between plasma cortisol levels and platelet 5-HT concentrations . Dexamethasone administration did not affect platelet 5-HT concentrations within subtypes of depressed patients . Abnormal cortisol suppression after the DST occurred more frequently in psychotic than in non-psychotic patients . Platelet 5-HT and plasma cortisol concentrations were decreased in patients with pronounced suicidal behaviour . Our results suggest that plasma cortisol and platelet 5-HT concentrations might serve as independent biological markers for different subtypes of depression Background and Purpose — Depression may be a risk factor for cardiovascular disease ( CVD ) mortality . We evaluated long-term mortality risk associated with depressive symptoms measured at middle age among men at high risk for coronary heart disease ( CHD ) . Methods — 12 866 men without definite evidence of CHD at study entry but who had above average risk of CHD based on blood pressure , blood cholesterol levels , and /or cigarette smoking were recruited into the Multiple Risk Factor Intervention Trial ( MRFIT ) . Survivors at the end of the trial were followed-up for mortality for an additional 18 years . Men who had completed the Center for Epidemiologic Studies Depression ( CES-D ) scale near the end of the trial ( n=11 216 ) were used in a prospect i ve analysis of post-trial all-cause and cause-specific mortality during 18-year follow-up after CES-D assessment . Results — Greater depressive symptoms measured at the end of the trial were associated with significantly higher risk of all-cause mortality and for cause-specific death , a higher risk of CVD , and , more specifically , stroke mortality ( all P values < 0.02 ) but not CHD mortality ( P=0.48 ) in linear trend analyses . The significant associations were strongest for those reporting the greatest depression : hazard ratio (HR)=1.15 ( 95 % CI , 1.03 to 1.28 ; P<0.01 ) for all-cause mortality for those in the highest depressive symptom quintile , HR=1.21 for CVD mortality ( 95 % CI , 1.03 to 1.41 ; P<0.05 ) , and HR=2.03 for stroke mortality ( 95 % CI , 1.20 to 3.44 ; P<0.01 ) compared with those in the lowest quintile . These associations were adjusted for age , intervention group , race , educational attainment , smoking at baseline and visit 6 , trial averaged systolic blood pressure , alcohol consumption , and fasting cholesterol , as well as the occurrence of nonfatal cardiovascular events during the trial . Conclusions — Greater depressive symptoms are associated with an increase in the risk of all-cause and , more specifically , CVD mortality in men . Stroke but not CHD was the form of CVD with which depressive symptoms were associated Background and Purpose — This study examined depressive disorder as a risk factor for incident stroke in a prospect i ve , population -based design . Methods — The Baltimore Epidemiologic Catchment Area Study is a prospect i ve 13-year follow-up of a probability sample of household residents from Baltimore , Md. Depressive disorder was measured with the diagnostic interview schedule , and stroke was assessed by questions from the health interview survey or by documentation on a death certificate . Results — During the 13-year follow-up of 1703 individuals , 66 strokes were reported and 29 strokes were identified by death certificate search . Individuals with a history of depressive disorder were 2.6 times more likely to report stroke than those without this disorder after controlling for heart disease , hypertension , diabetes , and current and previous use of tobacco . Medications used in the treatment of depressive disorder at baseline did not alter this finding . A history of dysthymia demonstrated a similar relationship to stroke , although the estimate was not statistically significant . Conclusions — Depressive disorder is a risk factor for stroke that appears to be independent of traditional cardiovascular risk factors . Further research on mechanisms for the association and the impact of treatment for depressive disorder on subsequent stroke is needed CONTEXT Depressive symptoms predict adverse cardiovascular outcomes in patients with coronary heart disease , but the mechanisms responsible for this association are unknown . OBJECTIVE To determine why depressive symptoms are associated with an increased risk of cardiovascular events . DESIGN AND PARTICIPANTS The Heart and Soul Study is a prospect i ve cohort study of 1017 out patients with stable coronary heart disease followed up for a mean ( SD ) of 4.8 ( 1.4 ) years . SETTING Participants were recruited between September 11 , 2000 , and December 20 , 2002 , from 12 outpatient clinics in the San Francisco Bay Area and were followed up to January 12 , 2008 . MAIN OUTCOME MEASURES Baseline depressive symptoms were assessed using the Patient Health Question naire ( PHQ ) . We used proportional hazards models to evaluate the extent to which the association of depressive symptoms with subsequent cardiovascular events ( heart failure , myocardial infa rct ion , stroke , transient ischemic attack , or death ) was explained by baseline disease severity and potential biological or behavioral mediators . RESULTS A total of 341 cardiovascular events occurred during 4876 person-years of follow-up . The age-adjusted annual rate of cardiovascular events was 10.0 % among the 199 participants with depressive symptoms ( PHQ score > or = 10 ) and 6.7 % among the 818 participants without depressive symptoms ( hazard ratio [ HR ] , 1.50 ; 95 % confidence interval , [ CI ] , 1.16 - 1.95 ; P = .002 ) . After adjustment for comorbid conditions and disease severity , depressive symptoms were associated with a 31 % higher rate of cardiovascular events ( HR , 1.31 ; 95 % CI , 1.00 - 1.71 ; P = .04 ) . Additional adjustment for potential biological mediators attenuated this association ( HR , 1.24 ; 95 % CI , 0.94 - 1.63 ; P = .12 ) . After further adjustment for potential behavioral mediators , including physical inactivity , there was no significant association ( HR , 1.05 ; 95 % CI , 0.79 - 1.40 ; P = .75 ) . CONCLUSION In this sample of out patients with coronary heart disease , the association between depressive symptoms and adverse cardiovascular events was largely explained by behavioral factors , particularly physical inactivity Aortic pulse wave velocity ( PWV ) is a significant and independent predictor of cardiovascular mortality in subjects with essential hypertension and in patients with end-stage renal disease . Its contribution to cardiovascular risk in subjects 70 to 100 years old has never been tested . A cohort of 141 subjects ( mean±SD age , 87.1±6.6 years ) was studied in 3 geriatrics departments in a Paris suburb . Together with sphygmomanometric blood pressure measurements , aortic PWV was measured with a vali date d automatic device . During the 30-month follow-up , 56 patients died ( 27 from cardiovascular events ) . Logistic regressions indicated that age ( P = 0.005 ) and a loss of autonomy ( P = 0.01 ) were the best predictors of overall mortality . For cardiovascular mortality , aortic PWV was the major risk predictor ( P = 0.016 ) . The odds ratio was 1.19 ( 95 % confidence interval , 1.03 to 1.37 ) . Antihypertensive drug treatment and blood pressure , including systolic and pulse pressure , had no additive role . In subjects 70 to 100 years old , aortic PWV is a strong , independent predictor of cardiovascular death , whereas systolic or pulse pressure was not . This prospect i ve result will need to be confirmed in an intervention trial BACKGROUND AND PURPOSE Evidence is mounting linking cerebrovascular disease with depressive symptoms in the elderly . Lesions in both white and gray matter have been associated with depressive symptoms and major depression . We sought to investigate the relationship between depressive symptoms and white and gray matter lesions in subjects participating in the Cardiovascular Health Study . METHODS In a sample of 3660 men and women who underwent a st and ardized interview , physical examination , and MRI scan , we examined the association between number of white and gray matter lesions and white matter grade ( a measure of severity ) and reported depressive symptoms using a modified version of the Centers for Epidemiologic Studies Depression ( CES-D ) scale . We controlled for a variety of demographic and medical variables as well as functional status and Modified Mini-Mental State Examination score . RESULTS The number of small ( <3 mm ) basal ganglia lesions was significantly associated with reported depressive symptoms , but white matter grade was not . In subsequent logistic regression models , number of basal ganglia lesions remained a significant predictor after controlling for non-MRI variables and severity of white matter lesions . CONCLUSIONS Our findings extend previous reports that linked cerebrovascular changes to depressive symptoms in clinical population s to a large community-based population . This report provides further evidence of the importance of basal ganglia lesions in geriatric depression Background Availability of a range of techniques and devices allow measurement of many variables related to the stiffness of large or medium sized arteries . There is good evidence that , pulse wave velocity is a relatively simple measurement and is a good indicator of changes in arterial properties . The pulse wave velocity calculated from pulse wave recording by other methods like doppler or tonometry is tedious , time-consuming and above all their reproducibility depends on the operator skills . It requires intensive re source involvement . For epidemiological studies these methods are not suitable . The aim of our study was to clinical ly evaluate the validity and reproducibility of a new automatic device for measurement of pulse wave velocity that can be used in such studies . Methods In 44 subjects including normal healthy control and patients with coronary artery disease , heart brachial , heart ankle , brachial ankle and carotid femoral Output:	A complex pattern of systemic immune activation , endothelial dysfunction and HPA axis hyperactivity is suggestive of the biological relationship between CVD and depression subtypes .
MS21977	*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 Primary care physicians are increasingly being asked to participate in postal surveys . Difficulties in achieving adequate response rates among physicians have been reported . We investigated the effect of two low-cost interventions on response to a primary care physician postal question naire . STUDY DESIGN AND SETTING A 2x2 factorial trial was developed within the context of a national survey assessing views and practice s of physicians regarding prostate-specific antigen testing . We evaluated question naire order ( version 1 : demographics first , version 2 : topic-specific questions first ) and written precontact . A national data base of primary care physicians was compiled . One thous and five hundred ninety-nine physicians were r and omly selected , stratified by health board , and r and omized . RESULTS 47.9 % of eligible physicians completed a question naire . There was a statistically significant 5.1 % higher response rate among physicians receiving version 1 of the question naire than those receiving version 2 ( 50.6 % vs. 45.4 % , P=0.05 ) ; the adjusted odds of response were significantly raised ( odds ratio=1.24 ; 95 % confidence interval=1.01 - 1.54 ) . Precontact result ed in a nonsignificant 3.6 % increase in response ( 49.8 % vs. 46.2 % ; P=0.16 ) . The interventions did not interact . CONCLUSION Ordering question naires with general questions first can significantly increase response rates , whereas precontact can achieve a modest increase . These strategies may enhance response while adding little to the cost of a physician survey PURPOSE This study compared the response time , response rate , and cost of two types of survey administration techniques : e-mail/web-based versus conventional postal mail . The main aim of the survey was to collect descriptive information on the existence of Acute Care for Elders units and their characteristics by surveying geriatric division chiefs . DESIGN AND METHODS Two r and omized cohorts of geriatric division chiefs were formed to receive a survey either by electronic mail ( n = 57 ) or by conventional postal mail ( n = 57 ) . If there was no response to the initial mailing , two follow-up mailings were sent to both groups using the original modality ; a third follow-up was performed using the alternative modality . For each group , response rate and response time were calculated . The average total cost was computed and compared across two groups . RESULTS The aggregate response rate was 58 % ( n = 31 ) for the e-mail group versus 77 % ( n = 44 ) for the postal mail group . The overall average response time was shorter in the e-mail group , 18 days compared with 33 days for the conventional postal mailing group . The cost comparison showed that average cost was $ 7.70 for the e-mail group , compared to $ 10.50 per response for the conventional mail group . IMPLICATION S It appears that although the web-based technology is gaining popularity and leads to lower cost per response , the conventional postal method of surveying continues to deliver a better response rate among the geriatric medicine division chiefs . The web-based approach holds promise given its lower costs and acceptable response rate combined with the shorter response time Background Low response rates among surgeons can threaten the validity of surveys . Internet technologies may reduce the time , effort , and financial re sources needed to conduct surveys . Objective We investigated whether using Web-based technology could increase the response rates to an international survey . Methods We solicited opinions from the 442 surgeon – members of the Orthopaedic Trauma Association regarding the treatment of femoral neck fractures . We developed a self-administered question naire after conducting a literature review , focus groups , and key informant interviews , for which we used sampling to redundancy techniques . We administered an Internet version of the question naire on a Web site , as well as a paper version , which looked similar to the Internet version and which had identical content . Only those in our sample could access the Web site . We alternately assigned the participants to receive the survey by mail ( n=221 ) or an email invitation to participate on the Internet ( n=221 ) . Non-respondents in the mail arm received up to three additional copies of the survey , while non-respondents in the Internet arm received up to three additional requests , including a final mailed copy . All participants in the Internet arm had an opportunity to request an emailed Portable Document Format ( PDF ) version . Results The Internet arm demonstrated a lower response rate ( 99/221 , 45 % ) than the mail question naire arm ( 129/221 , 58 % ) ( absolute difference 13 % , 95 % confidence interval 4%-22 % , P<0.01 ) . Conclusions Our Internet-based survey to surgeons result ed in a significantly lower response rate than a traditional mailed survey . Research ers should not assume that the widespread availability and potential ease of Internet-based surveys will translate into higher response rates BACKGROUND Historically , achieving a high response rate on physician surveys has been a challenging task . Given such concerns , underst and ing research strategies that facilitate adequate response rates is important . Primary care physician responses to a mail survey on smoking cessation are summarized by physician specialty and timing of incentive . METHODS A stratified r and om- sample design , stratified by patient population s-adults , adolescents , and pregnant women-was used . The sampling frame included New Jersey internists , general practitioners , family physicians , pediatricians , and obstetrician-gynecologists . A total of 2100 physicians , 700 physicians from each patient strata , were sample d and mailed a smoking-cessation survey in summer 2002 . The sample was r and omized by incentive timing : Half received the incentive ( i.e. , 25 dollars gift card ) with the first survey mailing , and half received the incentive on receipt of their completed survey . RESULTS The promised-incentive group achieved a significantly lower response rate ( 56 % ) compared with the up-front-incentive group ( 71.5 % ) . Response rates by medical specialty varied overall and within incentive groups . The difference between the incentive groups was greatest among obstetrician-gynecologists ( i.e. , 20.2 percentage points ) and was least among pediatricians ( i.e. , 5.8 percentage points ) . CONCLUSIONS Physician response rates to mail surveys are greatly improved , especially among certain medical specialties , by using up-front incentives Background The use of Internet-based question naires for collection of data to evaluate patient education and other interventions has increased in recent years . Many self-report instruments have been vali date d using paper- and -pencil versions , but we can not assume that the psychometric properties of an Internet-based version will be identical . Objectives To look at similarities and differences between the Internet versions and the paper- and -pencil versions of 16 existing self-report instruments useful in evaluation of patient interventions . Methods Participants were recruited via the Internet and volunteered to participate ( N=397 ) , after which they were r and omly assigned to fill out question naires online or via mailed paper- and -pencil versions . The self-report instruments measured were overall health , health distress , practice mental stress management , Health Assessment Question naire ( HAQ ) disability , illness intrusiveness , activity limitations , visual numeric for pain , visual numeric for shortness of breath , visual numeric for fatigue , self-efficacy for managing disease , aerobic exercise , stretching and strengthening exercise , visits to MD , hospitalizations , hospital days , and emergency room visits . Means , ranges , and confidence intervals are given for each instrument within each type of question naire . The results from the two question naires were compared using both parametric and non-parametric tests . Reliability tests were given for multi-item instruments . A separate sample ( N=30 ) filled out identical question naires over the Internet within a few days and correlations were used to assess test-retest reliability . Results Out of 16 instruments , none showed significant differences when the appropriate tests were used . Construct reliability was similar within each type of question naire , and Internet test-retest reliability was high . Internet question naires required less follow-up to achieve a slightly ( non-significant ) higher completion rate compared to mailed question naires . Conclusions Among a convenience sample recruited via the Internet , results from those r and omly assigned to Internet participation were at least as good as , if not better than , among those assigned mailed question naires , with less recruitment effort required . The instruments administered via the Internet appear to be reliable , and to be answered similarly to the way they are answered when they are administered via traditional mailed paper question naires Background Postal surveys are a frequently used method of data collection in health services research . Low response rates increase the potential for bias and threaten study validity . The objectives of this study were to estimate current response rates , to assess whether response rates are falling , to explore factors that might enhance response rates and to examine the potential for non-response bias in surveys mailed to healthcare professionals . Methods A r and om sample of postal or electronic surveys of healthcare workers ( 1996 - 2005 ) was identified from Medline , Embase or Psycinfo data bases or Biomed Central . Outcome measures were survey response rate and non response analysis . Multilevel , multivariable logistic regression examined the relationship between response rate and publication type , healthcare profession , country and number of survey participants , question naire length and use of reminders . Results The analysis included 350 studies . Average response rate in doctors was 57.5 % ( 95%CI : 55.2 % to 59.8 % ) and significantly lower than the estimate for the prior 10 year period . Response rates were higher when reminders were sent ( adjusted OR 1.3 ; 95%CI 1.1 - 1.6 ) but only half the studies did this . Response rates were also higher in studies with fewer than 1000 participants and in countries other than US , Canada , Australia and New Zeal and . They were not significantly affected by publication type or healthcare profession ( p > 0.05 ) . Only 17 % of studies attempted assessment of possible non-response bias . Conclusion Response rates to postal surveys of healthcare professionals are low and probably declining , almost certainly leading to unknown levels of bias . To improve the informativeness of postal survey findings , research ers should routinely consider the use of reminders and assess potential for non-response bias OBJECTIVES To compare 3 communication modes ( postal , fax , and e-mail ) in a rotavirus vaccine physician survey . METHODS We used 3 communication modes to distribute a survey to physicians listed in the membership directory of the Georgia Chapter of the American Academy of Pediatrics . The directory listed 1391 members ; however , 404 were deemed ineligible on the basis of their listing as a specialist , retiree , resident in training , or government public health employee . Of the 987 members expected to administer vaccines , 150 were selected r and omly to receive the postal survey ( postal group ) . Of the remaining listings , 488 ( 58 % ) of 837 listed a fax number ; 150 members were selected r and omly and faxed a survey ( fax group ) . Of the remaining members , 266 ( 39 % ) of 687 had e-mail addresses listed ; 150 members were selected r and omly for the e-mail survey ( e-mail group ) . A follow-up survey was sent by the same mode at 2 weeks . A final survey was sent via another mode ( mixed mode ) at 1 month : by fax to e-mail and postal nonresponders and by post to fax nonresponders and those without fax . RESULTS Eligible respondents in the 3 survey groups were similar in their practice setting and location . Although the e-mail group had fewer median years ( 8 years ) since medical school graduation than the fax group ( 19 years ) and postal group ( 17 years ) , a similar percentage of responders in all groups had computers ( > 85 % ) and Internet access ( > or = 70 % ) at work . However , only 39 % of members listed an e-mail address in the directory . In the 2 weeks after the first mailing , 39 surveys were completed via postal mail , 50 via fax , and 16 via e-mail . In the 2 weeks after the second contact ( sent at 2 weeks ) , 20 surveys were completed via postal mail , 15 via fax , and 17 via e-mail . The response rate after the first 2 mailings was 41 % ( 59 of 143 ) for postal , 47 % ( 65 of 137 ) for fax , and 26 % ( 33 of 125 ) for e-mail surveys . The third and final survey ( sent 1 month after the first mailing ) was sent by a different ( ie , mixed ) mode and elicited an additional 73 responses : 19 responses ( 15 postal , 4 fax ) from the postal group , 19 responses ( 18 postal , 1 fax ) from the fax group , and 35 responses ( 15 postal , 13 fax , 7 e-mail ) from the e-mail group . Twenty-three percent ( 9 of 40 ) of the e-mail and 18 % ( 15 of 83 ) of the fax surveys completed were returned on the same or subsequent day they were sent , compared with none of the postal surveys . There were significant differences among the 3 groups for invalid addresses/numbers ( 4 % postal , 8 % fax , and 16 % e-mail ) listed in the directory . Using mixed modes as the third contact , the overall response rate increased from 39 % before mixed mode to a final of 53 % . On the basis of the 3 initial groups , responses to 1 of 12 rotavirus questions differed significantly . CONCLUSIONS Future use of e-mail surveys in selected circumstances is promising , because the majority of providers have Internet access and acknowledged interest in participating in e-mail surveys . E-mail surveys could be especially useful if rapid response time is necessary . There were fewer incomplete questions by participants who completed the e-mail survey compared with postal or fax participants . Updating membership e-mail addresses and routinely using e-mail as a communication tool should improve the ability to use e-mail surveys . There may need to be ongoing evaluations that critically Output:	The systematic review suggested that monetary incentives and paper ( vs web or email ) surveys increase response rates . We conclude that in addition to monetary incentives and paper surveys , physician-to-physician follow-up telephone calls are an effective method to increase response rates in oncology-focused physician surveys
MS21978	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background This study aim ed to evaluate the associations of selected demographic , individual , social , and environmental factors with moderate-to-vigorous physical activity ( MVPA ) in a sample of children and adolescents . Methods MVPA was assessed among youth ( n = 294 ) 10 - 17-years-old using the ActiGraph accelerometer . Youth completed measures of demographic and individual variables related to physical activity ( PA ) , perceived social support by parents and peers , and perceived neighborhood characteristics . Parents completed the long-form of the International Physical Activity Question naire . The Physical Activity and Media Inventory was used to measure the home environment and Geographical Information Systems software was used to measure the physical neighborhood environment . Bivariate correlations and hierarchical multiple regression were conducted stratified by gender . Results Boys participated in significantly more MVPA than girls . In hierarchical analyses , peer support , home PA equipment , and temperature were significantly associated with MVPA among boys whereas distance to the school they attended was associated with MVPA among girls . The final models accounted for 25 % and 15 % of the variance in MVPA among boys and girls , respectively . Conclusions Important differences exist among the individual , social , and environmental factors related to MVPA between boys and girls . Boys ' levels of activity appear to be influenced by factors closely linked to unstructured and social types of activities whereas girls ' activities relate to internal and external barriers as well as their proximity to their schools . The prospect i ve contribution of these important individual , social , and environmental factors to changes in MVPA among children and adolescents remains to be determined BACKGROUND Underst and ing the determinants of physical activity in children is critical for the treatment and prevention of childhood obesity . Social-cognitive theory has been used to underst and behavioral patterns in children . OBJECTIVES To explore the relationship between health beliefs , self-efficacy , social support , and sedentary activities and physical activity levels in children and to examine the relationship between physical activity and children 's self-esteem . METHODS Ninety-two children aged 10 to 16 years completed the study . Physical activity was monitored for 1 week with a motion detector ( Actitrac ; IM Systems , Baltimore , Md ) . Moderate-level activity and high-level activity were defined based on the results of treadmill testing . Health beliefs , self-efficacy , social influences , and time spent in sedentary behaviors were determined through question naires . Self-esteem was measured using the Piers-Harris Children 's Self-Concept Scale . Chronic anxiety was measured with the Revised Children 's Manifest Anxiety Scale . RESULTS There was a significant decline in physical activity levels between ages 10 and 16 years , particularly in girls . Preteen girls spent approximately 35 % more time in low- and high-level activity than did teenage girls ( P<.001 ) . Overall , children spent 75.5 % of the day inactive , with a mean + /- SD of 5.2 + /- 1.8 hours watching television , sitting at the computer , and doing homework . In contrast , only 1.4 % of the day ( 12.6 + /- 12.2 minutes ) was spent in vigorous activity . Time spent in sedentary behaviors was inversely correlated with the amount of moderate-level activity ( P<.001 ) but not high-level activity . In contrast , time spent in high-level activity correlated with self-efficacy scores ( P<.001 ) and social influences scores ( P<.005 ) . High-level physical activity was also associated with improved self-esteem ( P<.05 ) . Higher health beliefs scores were not correlated with physical activity levels . CONCLUSIONS Children and adolescents are largely sedentary . Correlates of high- and low-level physical activity are different . Time spent on sedentary activities is inversely correlated with moderate-level activity , while self-efficacy and social influences are positively correlated with more intense physical activity . In addition , increased high-level physical activity is an important component in the development of self-esteem in children OBJECTIVE To test whether self-efficacy for overcoming barriers to physical activity has direct , indirect ( i.e. , mediated ) , or moderating relations with naturally occurring change in perceived social support and declines in physical activity during high school . METHODS Latent growth modeling was used with measures completed in the 8th , 9th , and 12th grade s by a cohort of 195 Black and White girls . RESULTS Self-efficacy was stable and moderated the relation between changes in physical activity and perceived social support . Girls who maintained a perception of strong social support had less of a decline in physical activity if they also had high self-efficacy . However , girls having high self-efficacy had a greater decline in physical activity if they perceived declines in social support . CONCLUSIONS R and omized controlled trials of physical activity interventions based on social cognitive theory should consider that the influence of girls ' perceptions of social support on their physical activity may differ according to their efficacy beliefs about barriers to physical activity OBJECTIVE To identify factors associated with changes in physical activity in adolescent girls at risk for sedentary lifestyles and obesity . DESIGN A cohort study was performed with 201 high school girls recruited to participate in an evaluation study of a school-based obesity prevention physical education program . Three assessment s were performed during an 8-month period . MAIN OUTCOME MEASURES Associations between physical activity and a range of personal factors ( self-acceptance , self-worth , athletic competence , body image , depressive mood , perceived benefits , enjoyment of physical activity , self-efficacy , and body mass index ) , behavioral factors ( watching television and time constraints ) , and socioenvironmental factors ( social support and costs/re sources ) were assessed . RESULTS The 2 strongest and most consistent factors associated with change in physical activity were time constraints and support for physical activity from peers , parents , and teachers . Measures assessing self-perceptions , global ( ie , self-worth ) and specific to physical activity ( ie , self-efficacy to be physically active ) , were also associated with change in physical activity . For example , a decrease of 2.0 U for an adolescent 's perceived time constraints ( possible range , 3.0 - 12.0 U ) would be expected to lead to an increase of 53 minutes of moderate to vigorous physical activity per week ( 95 % confidence interval , 33 - 72 minutes ) . An increase of 2.0 U in perceived support for physical activity ( possible range , 3.0 - 12.0 U ) would be expected to lead to an increase of 35 minutes of moderate to vigorous physical activity per week ( 95 % confidence interval , 13 - 56 minutes ) . An increase of 3.0 U on the self-worth scale ( possible range , 5.0 - 20.0 U ) might be expected to lead to an increase of 19 minutes of moderate to vigorous physical activity per week ( 95 % confidence interval , 0 - 40 minutes ) . CONCLUSION The effectiveness of interventions aim ed at increasing physical activity among adolescent girls might be enhanced by engaging support from friends , family , and caring adults ; addressing real and perceived time constraints ; and helping adolescent girls feel more confident about themselves and their ability to engage in physical activity 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 The aim of this study was to examine modifiable biological , psychological , behavioral and social-environmental correlates of physical activity among 1129 Norwegian 11-year-old children within a cross-sectional sample from the HEalth In Adolescents study . Physical activity was assessed by accelerometer , and weight and height were measured objective ly . Age- and gender-specific cut-off points proposed by the International Obesity Task Force were used to define body mass index . Social-environmental variables were self-reported by question naire . Hierarchical regression ( linear mixed models ) revealed that normal weight children scored higher on percentage daily moderate-to-vigorous physical activity [ % daily moderate to vigorous physical activity ( MVPA ) ] than overweight/obese children ( P<0.001 ) . Self-efficacy ( P<0.01 ) and perceived social support from friends ( P<0.01 ) were positively associated with children 's % daily MVPA , and a negative association was found for computer/game-use on weekends ( P<0.01 ) . A moderator effect of weight category ( normal vs overweight/obese ) in the relationship between computer/game-use on weekends and % daily MVPA was detected ( P<0.05 ) , reflecting that higher computer/game-use on weekends was associated with lower % MVPA among the overweight/obese , but not among the normal weight . Modifiable correlates from multiple domains accounted for 14 % of the variance in % daily MVPA . Prospect i ve and intervention studies are needed to examine whether these factors act as mediators for physical activity change in pre-adolescent children OBJECTIVE This study examined differences in ( 1 ) psychosocial correlates of physical activity and in ( 2 ) physical activity within different context s and sedentary behaviors between normal weight and overweight adolescents . It further explored whether the prediction of physical activity by the psychosocial correlates is different in normal weight and overweight adolescents . RESEARCH METHODS AND PROCEDURE A community sample of 6078 11 to 19 year olds from 38 secondary schools , which were r and omly selected throughout the country , completed a vali date d computerized question naire about physical activity , sedentary behaviors , and psychosocial correlates . Differences in mean scores on the psychosocial correlates and on the self-rated physical activity were analyzed between the normal weight ( n=5563 ) and the overweight ( n=515 , 8.5 % ) group . RESULTS This study showed that overweight adolescents do less intense physical activities ( p<0.001 ) and have less favorable psychosocial correlates related to physical activity ( p<0.001 ) than their normal weight counterparts . However , the strength of the associations between psychosocial variables and total physical activity were comparable in overweight and normal weight adolescents . More support from family and friends , more fun in physical activity , higher self-efficacy , the perception of more competition benefits , and the perception of less lack of interest were all associated with higher total levels of physical activity . The results suggest that no specific tailoring on psychosocial correlates of physical activity is necessary for overweight adolescents compared with normal weight ones . DISCUSSION Both overweight and normal weight adolescents can be approached by interventions focusing on the same psychosocial variables to increase physical activity The present study examined whether self-efficacy mediates the relationship between family social influence and physical activity among youth who have experienced a recent lapse in their physical activity participation . Using a prospect i ve , longitudinal design , participants completed measures of social influence , self-regulatory efficacy and physical activity . Only those participants whose physical activity declined were retained for further analysis . Self-regulatory efficacy partially mediated the relationship between family social influence and physical activity , with self-efficacy mediating 36 percent of the total effect . The results provide support for self-regulatory efficacy as a mediator and provide preliminary insight into the potential mechanisms for preventing lapses in activity from developing into prolonged periods of inactivity within this population OBJECTIVE To determine if perceptions of the social and physical environment are associated with active transport and leisure-time sports among Belgian youth and to investigate if this relationship is moderated by self-efficacy . METHODS In February-May 2008 , 1445 adolescents ( 17.4+/-0.6 yrs ) were recruited in 20 r and omly selected Belgian schools . Physical activity , psychosocial , and environmental factors were assessed using vali date d question naires . Moderated multilevel regression analysis was used to examine the association between physical activity and possible correlates . RESULTS Social environmental variables ( modeling and social support ) were positively associated with active transportation and leisure-time sports ( p<0.05 ) . Higher l and use mix diversity , higher street connectivity , more attractive environments Output:	Social support was positive and consistently associated with the physical activity level of adolescents in cross-sectional and longitudinal studies . Those who received more overall social support as well as support from both parents , friends and family showed higher levels of physical activity .
MS21979	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES The study aim ed to test two hypotheses . Firstly , that participants who relapsed during the 12-month follow-up period of our r and omized controlled trial , would show increased negative beliefs about their illness and reduced self-esteem , in comparison to the non-relapsed participants . Secondly , that cognitive behavioural therapy ( CBT ) for early signs of relapse would result in a reduction in negative beliefs about psychosis and an improvement in self-esteem at 12 months . DESIGN AND METHODS A total of 144 participants with schizophrenia or a related disorder were r and omized to receive either treatment as usual ( TAU ; N=72 ) or CBT ( N=72 ) . Participants completed the Personal Beliefs about Illness Question naire ( PBIQ ; Birchwood , Mason , MacMillan , & Healy , 1993 ) and the Rosenberg Self-Esteem Scale ( RSES ; Rosenberg , 1965 ) at entry , 3 months , 6 months , and 12 months . RESULTS At 12 months , relapsers showed greater increase in scores for PBIQ entrapment compared with non-relapsers . In addition , after controlling for baseline covariates ( treatment group and PBIQ self versus illness ) , relapsers also showed greater increase in scores for PBIQ self versus illness at 12 months . Furthermore , in comparison to treatment as usual , participants who received CBT showed greater improvement in PBIQ loss and in Rosenberg self-esteem . CONCLUSIONS The study provides evidence that relapse is associated with the development of negative appraisal s of entrapment and self-blame ( self vs. illness ) . In addition , this is the first study to show that CBT reduces negative appraisal s of loss arising from psychosis and improvements in self-esteem . Implication s for future research and treatment are discussed 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 Patient-rated unmet need is cross-sectionally associated with quality of life . Its longitudinal relationship has not been established . AIMS To test the hypotheses that : ( a ) higher patient-rated unmet need is associated with lower individual quality of life assessment s by a patient over time ; and ( b ) reduction in patient-rated unmet need precedes improvement in quality of life . METHOD One hundred and one individuals using adult mental health services were asked to complete 6-monthly question naires , comprising quality of life ( Manchester Short Assessment of Quality of Life , MANSA ) and unmet need ( Camberwell Assessment of Need Short Appraisal Schedule , CANSAS ) assessment s. RESULTS Seventy-three participants provided 240 separate pairs of consecutive assessment s. R and om effects regression models indicated an impact on current quality of life for both average level of unmet need ( B= -0.23 , 95 % CI -0.29 to -0.17 ) and change in unmet need over the past month ( B= -0.04 , 95 % CI -0.02 ) . CONCLUSIONS Changes in patient-rated unmet needs may cause changes in quality of life BACKGROUND Patient-clinician communication is central to mental healthcare but neglected in research . AIMS To test a new computer-mediated intervention structuring patient-clinician dialogue ( DIALOG ) focusing on patients ' quality of life and needs for care . METHOD In a cluster r and omised controlled trial , 134 keyworkers in six countries were allocated to DIALOG or treatment as usual ; 507 people with schizophrenia or related disorders were included . Every 2 months for 1 year , clinicians asked patients to rate satisfaction with quality of life and treatment , and request additional or different support . Responses were fed back immediately in screen displays , compared with previous ratings and discussed . Primary outcome was subjective quality of life , and secondary outcomes were unmet needs and treatment satisfaction . RESULTS Of 507 patients , 56 were lost to follow-up and 451 were included in intention-to-treat analyses . Patients receiving the DIALOG intervention had better subjective quality of life , fewer unmet needs and higher treatment satisfaction after 12 months . CONCLUSIONS Structuring patient-clinician dialogue to focus on patients ' views positively influenced quality of life , needs for care and treatment satisfaction Nonadherence to medication is a widespread problem in schizophrenia and is associated with poor clinical outcomes and inappropriate management and utilization of re sources . The aim of the current investigation was to assess the impact of telemonitoring of medication adherence on symptomatology and service use in patients with schizophrenia . A total of 108 schizophrenia patients were r and omized into three equal groups according to the approaches used to assess medication adherence ; self-report , pill counting , and telemonitoring . Telementoring was achieved through an innovative new platform called @HOME . This platform offers clinicians early warnings about impeding nonadherence as well as information about the pattern of medication taking . Patient 's adherence was observed over an 8-week period , during which patient 's clinical status and service use were recorded . In comparison to the other two groups , patients using @HOME showed improvement in the Global Clinical Impression Scale and a significant reduction in emergency visits and medical appointments . The @HOME platform was highly acceptable by patients , caregivers , and professionals , and required minimal training for implementation . The results of the study suggest that the use of telemonitoring in psychiatric setting s was both feasible and acceptable and may be associated with significant clinical and service related benefits BACKGROUND : Interactive Health Communication Applications ( IHCAs ) are computer-based , usually web-based health information packages for patients that combine information with at least one of social support , decision support , or behaviour change support . These are innovations in health care and their effects on health are uncertain . OBJECTIVES : To assess the effects of IHCAs for people with chronic disease . SEARCH STRATEGY : We design ed a four-part search strategy . First , we search ed electronic bibliographic data bases for published work ; second , we search ed the grey literature and third , we search ed for ongoing and recently completed clinical trials in the appropriate data bases . Finally , research ers of included studies were contacted , and reference lists from relevant primary and review articles were followed up . As IHCAs require relatively new technology , the search commenced at 1990 where possible . SELECTION CRITERIA : R and omised controlled trials ( RCTs ) of Interactive Health Communication Applications for adults and children with chronic disease . DATA COLLECTION AND ANALYSIS : One review er screened abstract s. Two review ers screened all c and i date studies to determine eligibility , apply quality criteria , and extract data from included studies . Authors of included RCTs were contacted for missing data . Results of RCTs were pooled using a r and om effects model and st and ardised mean differences ( SMDs ) were calculated to provide net effect sizes . MAIN RESULTS : We screened 24,757 unique citations and retrieved 958 papers for further assessment , yielding 28 RCTs involving 4042 participants . One of these had an inadequate method of concealment of allocation , and sensitivity analyses were performed to determine the effects of including or excluding these data in the meta-analyses . Results in the abstract are from the meta-analyses excluding data from this study .IHCAs were found to have a positive effect on knowledge ( SMD 0.49 ; 95 % confidence interval ( CI ) 0.14 to 0.84 ) and on social support ( SMD 0.47 ; 95 % CI 0.28 to 0.66 ) . IHCAs were found to have no effect on self-efficacy ( SMD 0.15 ; 95 % CI -0.13 to 0.43 ) or behavioural outcomes ( SMD -0.09 ; 95 % CI -0.49 to 0.32 ) . IHCAs had a negative effect on clinical outcomes ( SMD -0.32 ; 95 % CI -0.63 to -0.02 ) . REVIEW ERS ' CONCLUSIONS : The number and range of IHCAs is increasing rapidly ; however there is a shortage of high quality evaluative data . Consumers who wish to increase their knowledge or social support amongst people with a similar problem may find an IHCA helpful . However , consumers whose primary aim is to achieve optimal clinical outcomes should not use an IHCA at present . Further research is needed to determine the reason for this negative effect on clinical outcomes , whether an optimal IHCA can achieve behaviour change and improved health outcomes , and if so , what are the essential features of such an IHCA , and the extent to which they differ according to patient group or condition BACKGROUND Preliminary results have demonstrated the clinical efficacy of computerised cognitive-behavioural therapy ( CBT ) in the treatment of anxiety and depression in primary care . AIMS To determine , in an exp and ed sample , the dependence of the efficacy of this therapy upon clinical and demographic variables . METHOD A sample of 274 patients with anxiety and /or depression were r and omly allocated to receive , with or without medication , computerised CBT or treatment as usual , with follow-up assessment at 6 months . RESULTS The computerised therapy improved depression , negative attributional style , work and social adjustment , without interaction with drug treatment , duration of preexisting illness or severity of existing illness . For anxiety and positive attributional style , treatment interacted with severity such that computerised therapy did better than usual treatment for more disturbed patients . Computerised therapy also led to greater satisfaction with treatment . CONCLUSIONS Computer-delivered CBT is a widely applicable treatment for anxiety and /or depression in general practice 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 Output:	Adding technology-mediated psychoeducation on top of st and ard care did not clearly improve either general mental state , negative or positive symptoms , global state , level of knowledge or quality of life . However , the results were not consistent regarding level of knowledge and satisfaction with treatment . Using ICT to deliver psychoeducational interventions has no clear effects compared with st and ard care , other methods of delivering psychoeducation and support , or both .
MS21980	*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 study was to investigate the efficacy and safety of Cerebrolysin in patients with hemorrhagic stroke . The primary objective of this trial was to assess the clinical efficacy and safety of a 10–days course of therapy with a daily administration of Cerebrolysin ( 50 mL Ⅳ per day ) . The trial had to demonstrate that Cerebrolysin treatment is safe in hemorrhagic stroke . Methods : The study was performed as a prospect i ve , r and omized , double blind , placebo – controlled , parallel group study with 2 treatment groups . Efficacy measures were the Unified Neurological Stroke Scale , Barthel Index , and Syndrome Short Test . The duration of the trial was of 21 days for each patient . Out of 100 r and omized patients , a total of 96 ( 96 % ) completed the study . Results : Overall , no statistically significant group effects were observed based on single average comparisons at the individual visits . It could be shown that the treatment of hemorrhagic stroke with Cerebrolysin is safe and well tolerated . Conclusion : In the changes of UNSS , BI and SST from baseline to day 21 , the group differences are not statistically significant ; however , the use of Cerebrolysin in hemorrhagic stroke is safe and well tolerated and studies with a larger sample size may provide statistical evidence of Cerebrolysin 's efficacy in patients with hemorrhagic stroke Summary . Background and purpose . Cerebrolysin is a compound with neurotrophic and neuroprotective activity . It is produced by enzymatic breakdown of purified brain proteins and consists of low molecular weight peptides and amino acids . Cellular and animal models of cerebral ischaemia have shown that it is a potent neuroprotective agent . We explored the safety and preliminary outcome of Cerebrolysin treatment in patients with acute stroke . Methods . R and omised , placebo-controlled , parallel group trial . Patients with acute stroke were r and omised within 24 h of stroke onset to IV therapy with placebo or Cerebrolysin 50 mL/day for 21 days . Both groups received concomitant treatment with ASA 250 mg/day PO and pentoxifylline 300 mg/day IV . Clinical examinations were performed on days 1 , 3 , 7 , 21 and 90 post baseline . Outcome measures were the Canadian Neurological Scale , the Barthel Index , the Clinical Global Impressions , the Mini-Mental State Examination , and the Syndrome Short Test . Treatment emergent adverse events , lab tests , and vital signs were recorded to assess the safety of Cerebrolysin . Results . 146 patients were enrolled in two groups : 78 Cerebrolysin and 68 placebo . At baseline , no significant group differences were observed . Patients in the Cerebrolysin group had no significant improvement in the CNS score , the Barthel Index and the Clinical Global Impressions when compared to the placebo group . A significant improvement of cognitive function of the patients on Cerebrolysin was observed in the Syndrome Short Test when compared to the placebo group . Cerebrolysin was well tolerated and safe . Adverse events occurred with a similar frequency in both groups . Conclusion . The results demonstrate that neurotrophic treatment with Cerebrolysin is safe and well tolerated by patients with acute stroke . The findings , despite the small sample size , also indicate a potential treatment effect of Cerebrolysin in acute stroke . Larger studies , however , are needed to confirm and extend these findings Background and Purpose — The aim of this trial was to investigate whether stroke patients who receive Cerebrolysin show improved motor function in the upper extremities at day 90 compared with patients who receive a placebo . Methods — This study was a prospect i ve , r and omized , double-blind , placebo-controlled , multicenter , parallel-group study . Patients were treated with Cerebrolysin ( 30 mL/d ) or a placebo ( saline ) once daily for 21 days , beginning at 24 to 72 hours after stroke onset . The patients also participated in a st and ardized rehabilitation program for 21 days that was initiated within 72 hours after stroke onset . The primary end point was the Action Research Arm Test score on day 90 . Results — The nonparametric effect size on the Action Research Arm Test score on day 90 indicated a large superiority of Cerebrolysin compared with the placebo ( Mann – Whitney estimator , 0.71 ; 95 % confidence interval , 0.63–0.79 ; P<0.0001 ) . The multivariate effect size on global status , as assessed using 12 different outcome scales , indicated a small-to-medium superiority of Cerebrolysin ( Mann – Whitney estimator , 0.62 ; 95 % confidence interval , 0.58–0.65 ; P<0.0001 ) . The rate of premature discontinuation was < 5 % ( 3.8 % ) . Cerebrolysin was safe and well tolerated . Conclusions — Cerebrolysin had a beneficial effect on function and global outcome in early rehabilitation patients after stroke . Its safety was comparable with that of the placebo , suggesting a favorable benefit/risk ratio . Because this study was exploratory and had a relatively small sample size , the results should be confirmed in a large-scale , r and omized clinical trial . Clinical Trial Registration — URL : http://www . clinical trialsregister.eu . Unique identifier : 2007 - 000870 - 21 Background The neurotrophic drug Cerebrolysin accelerated recovery and prevented acute neuronal damage in pre clinical models of ischaemia . Previous clinical trials support therapeutic effects in stroke patients . The study investigated whether the combination with alteplase and Cerebrolysin is safe and can further reduce disability after acute ischaemic stroke . Methods This placebo-controlled , double-blind trial involved 119 patients with acute ischaemic hemispheric stroke , r and omly assigned to a combined treatment with alteplase plus Cerebrolysin or placebo ( administered 1 h after thrombolytic treatment ) starting within three-hours after onset of symptoms . A daily i.v . infusion of 30 ml Cerebrolysin or placebo was given for 10 consecutive days . Primary outcome was the modified Rankin Scale at day 90 . A sequential design with interim analyses was applied . Results The third interim analysis did not show a benefit in the modified Rankin Scale for Cerebrolysin on day 90 compared to placebo and the study was stopped . The National Institutes of Health Stroke Scale responder analysis ( secondary outcome measure ) showed significantly more patients with an improvement of 6 or more points ( or a total score of 0 or 1 ) after two- , five- , 10 , and 30 days in the Cerebrolysin group . Similar trends were observed for the modified Rankin Scale responder analysis without achieving statistical significance . There was no difference between treatment groups regarding adverse events . Conclusions The combination of Cerebrolysin with recombinant tissue-Plasminogen Activator is safe for treatment of acute ischaemic stroke but did not improve outcome at day 90 . During the treatment period with Cerebrolysin ( 10 days ) , significantly more patients had a favourable response in neurological outcome measures ( National Institutes of Health Stroke Scale ) as compared to the placebo group Background Cerebrolysin , a brain-derived neuropeptide , has been shown to improve the neurological outcomes of stroke , but no study has demonstrated its effect on cerebral blood flow . This study aim ed to determine the cerebrolysin impact on the neurological outcomes and cerebral blood flow . Methods In a r and omized , double-blinded , placebo-controlled trial , 46 patients who had acute focal ischemic stroke were r and omly assigned into two groups to receive intravenously either 30 mL of cerebrolysin diluted in normal saline daily for 10 days ( n=23 ) or normal saline alone ( n=23 ) adjunct to 100 mg of aspirin daily . All patients were examined using the National Institutes of Health Stroke Scale and transcranial Doppler to measure the mean flow velocity and pulsatility index ( PI ) of their cerebral arteries at baseline as well as on days 30 , 60 , and 90 . Results The patients ’ mean age was 60±9.7 years , and 51.2 % of patients were male . The National Institutes of Health Stroke Scale was significantly lower in the cerebrolysin group compared with the placebo group on day 60 ( median 10 , interquartile range 9–11 , P=0.008 ) and day 90 ( median 11 , interquartile range 10–13.5 , P=0.001 ) . The median of PI in the right middle cerebral artery was significantly lower in the cerebrolysin group compared with the placebo group on days 30 , 60 , and 90 ( P<0.05 ) . One patient in the cerebrolysin group and two patients in the placebo group died before day 30 ( 4.3 % versus 8.7 % ) . Conclusion Cerebrolysin can be useful to improve the neurological outcomes and the PI of middle cerebral artery in patients with acute focal ischemic stroke Cerebrolysin has exhibited neuroprotective as well as neurotrophic properties in various animal models of cerebral ischaemia and has shown clinical efficacy and good safety in several small controlled clinical studies in ischaemic stroke . Therefore , a large double-blind placebo-controlled r and omized clinical trial was launched in Asia to prove the validity of this treatment strategy . In the more than 50 participating centres patients with acute ischemic hemispheric stroke are r and omized within 12 hours of symptoms onset to treatment ( 30 ml Cerebrolysin diluted in physiologic saline ) or placebo ( saline ) given as intravenous infusion once daily added to st and ard care for 10 days . The patients are followed with regular visits for 90 days . Efficacy is evaluated on day 90 by three outcome scales – modified Rankin Scale , Barthel Index and NIH Stroke Scale – combined to single global directional test . Additionally , adverse events are documented to prove safety . In this study a total of 1060 patients will be included and analysis of data will be completed in 2010 . If positive , this trial will add an effective strategy to the treatment of acute ischaemic stroke Background and Purpose Approved use of intravenous alteplase for ischemic stroke offers net benefit . Pooled r and omized controlled trial analysis suggests additional patients could benefit but others be harmed with treatment initiated beyond 4·5 h after stroke onset . We proposed prognostic scoring methods to identify a strategy for patient selection . Methods We selected 500 patients treated by intravenous alteplase and 500 controls from Virtual International Stroke Trials Archive , matching modified Rankin score outcomes to those from pooled r and omized controlled trial 4·5–6 h data . We ranked patients by prognostic score . We chose limits to optimize our sample for a net treatment benefit significant at P = 0·01 by Cochran – Mantel – Haenszel test and by ordinal regression . For validation , we had these applied to the pooled r and omized controlled trial data for 4·5–6 h , testing for net benefit by Cochran – Mantel – Haenszel test , ordinal regression , and also by dichotomized outcomes : modified Rankin score 0–1 , mortality and parenchymal hemorrhage type 2 bleeds . All analyses were adjusted for age and National Institutes of Health Stroke Scale . Results In the training data set , limits of 56–95 on a prognostic score retained 714 patients in whom there was net benefit significant at P = 0·01 . When applied to the 1120 patients in the pooled r and omized controlled trial 4·5–6 h data set , score limits of 56–95 retained 711 patients and gave odds ratio for improved modified Rankin score distribution of 1·13 , 95 % confidence interval 0·87–1·47 , Cochran – Mantel – Haenszel P = 0·89 . More patients achieved modified Rankin score 0–1 ( odds ratio 1·44 , 1·02–2·05 , P = 0·04 ) but mortality and parenchymal hemorrhage type 2 bleeds were increased : odds ratio 1·56 , 1·01–2·40 , P = 0·04 ; odds ratio 15·6 , 3·7–65·8 , P = 0·0002 , respectively . Conclusion Selection of patients between 4·5 and 6 h based on simple clinical measures failed to deliver a population in whom the alteplase effect would be safe and effective Background and Purpose — Cerebrolysin showed neuroprotective and neurotrophic properties in various pre clinical models of ischemia and small clinical trials . The aim of this large double-blind , placebo-controlled r and omized clinical trial was to test its efficacy and safety in patients with acute ischemic stroke . Methods — Patients with acute ischemic hemispheric stroke were r and omized within 12 hours of symptoms onset to active treatment ( 30 mL Cerebrolysin daily ) or placebo ( saline solution ) given as intravenous infusion for 10 days in addition to aspirin ( 100 mg daily ) . The patients were followed up to 90 days . The primary end point was the result of a combined global directional test of modified Rankin Scale , Barthel Index , and National Institutes of Health Stroke Scale . Adverse events were documented to assess safety . Results — A total of 1070 patients were enrolled in this study . Five hundred twenty-nine patients were assigned to Cerebro Output:	The findings of this Cochrane Review do not demonstrate clinical benefits of cerebrolysin for treating acute ischaemic stroke . We found moderate- quality evidence of an increase in non-fatal SAEs with cerebrolysin use but not in total SAEs
MS21981	*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 hypothesized that leg-length discrepancies of as little as 1 cm would induce a significant postural shift and increase the extent of postural sway . We had 14 normal volunteers st and on a force platform with their feet in a st and ard position . Center-of-pressure data were recorded at 100Hz for 20 seconds while the subjects stood barefoot with no lifts or ( in r and om order ) with lifts of 1 , 2 , 3 , and 4 cm under their left and right feet . From these data we derived the mean center-of-pressure position and the extent of postural sway . Lifts of as little as 1 cm shifted the mean center-of-pressure toward the longer leg to a statistically significant extent ( p less than 0.001 ) , the mean difference compared with the barefoot condition being 6.1 % of the distance between the feet ; increasing the discrepancy did not proportionately increase the effect . The postural sway ( total travel of the center-of-pressure ) in a mediolateral direction increased significantly with a 1 cm discrepancy ( p less than 0.01 ) , and continued to increase in proportion to the magnitude of the discrepancy . There were no effects on anteroposterior position or sway and no influence of left-right dominance . These results support our hypothesis that a leg-length discrepancy of as little as 1 cm may be biomechanically important Current surgery outcome evaluations in patients with Legg-Calvé-Perthes disease ( LCPD ) are usually based on static radiological changes . The aim of the present study was to assess the development of characteristic gait parameters and passive hip range of motion ( ROM ) measurements during the postoperative period up to healed stage of the femoral head represented by Stulberg classification . Twelve children ( 10 male , 2 female ) with unilateral diagnosis of LCPD and 19 healthy control subjects at the same age participated in this prospect i ve longitudinal study . Instrumented gait analysis was performed preoperatively , 13.4 ( ±1.7 ) , and 28.0 ( ±4.4 ) months postoperatively . At final follow-up , the mean leg length of the involved side was reduced by 1.10 (±0.53)cm compared to the non-involved side . In addition , a significant reduction in maximum knee flexion ( -26 % , p=0.037 ) and knee flexion/extension ROM ( -26 % , p=0.017 ) in stance was still present in the patient group compared to controls indicating a " stiff knee gait pattern " . In contrast , the sagittal plane hip parameters , the ipsilateral trunk lean toward the involved stance limb , and the knee and hip joint loading during gait normalized during the postoperative period . The results of the present study should motivate further exploration if patients with LCPD stiffen their knees to compensate for leg length discrepancy . Besides the st and ard radiological evaluation of the surgery outcome , instrumented gait analysis is a valuable method of recording functional deficits and early recognition of the need for physiotherapeutic treatment or insole supply in patients with LCPD Abstract The purpose of this study was to quantitatively evaluate the effects of experimental leg length discrepancies on body posture and dental occlusion . Thirty asymptomatic subjects ( 15 males and 15 females , ages 19 - 33 , mean age 25.6 years ) were included in this study and r and omly assigned to one of two groups based on a table of r and om numbers . The only difference between group A and group B was the sequence of testing . Experimental leg length discrepancies were provided by using ten types of insoles with heights ranging from one to ten mm at one mm intervals , placed under both feet . The MatScan ( Nitta Corp. , Osaka , Japan ) system was used to measure changes in body posture ( center of foot pressure : COP ) while subjects maintained the following three postural positions : 1 . natural st and ing posture ( control ) ; 2 . control with a heel lift under the right foot ; or 3 . control with a heel lift under the left foot . The T-Scan II system ( Nitta Corp. , Osaka , Japan ) was used to analyze the results of changes in dental occlusion ( center of occlusal force : COF ) in the above-mentioned three postural positions . When subjects used a heel lift of six mm or more under the right foot , lateral weight distribution ( LWD ) shifted to the right side compared to the control ( p<0.05 ) . When a heel lift of four mm or more was used under the left foot , LWD shifted to the left side compared to the control ( p<0.05 ) . When subjects used a heel lift of eight mm or more under the right foot , occlusal force shifted to the right side compared to the control ( p<0.05 ) . When subjects used a heel lift of seven mm or more under the left foot , occlusal force shifted to the left side compared to the control ( p<0.05 ) . Based on these findings , it was concluded that leg length discrepancy affected body posture and dental occlusion Acromegaly is a chronic debilitating disease that presents with multiple systemic manifestations , including changes in body composition , joint abnormalities , muscular impairment and visual disturbances . This study aim ed to assess posture and body balance in acromegalic patients and to establish the correlation between these measures . Twenty-eight acromegalic patients and a similar number of control subjects matched for sex , age , weight , height and body mass index underwent postural evaluation using the photogrammetry and measurement of balance using the stabilometry in two tasks : feet apart , eyes open and feet together , eyes closed . In comparison with the control group , the acromegalic group presented postural deviations in lateral views in the vertical alignment of the trunk ( P=0.001 for the right side and P=0.021 for the left ) , the hip angle ( P=0001 for the right side and P=0.016 for the left side ) and horizontal alignment of the pelvis ( P=0.017 for the right and P<0.001 for the left side ) . Compared with healthy subjects , the acromegalic patients presented displacement of the centre of pressure in both the anterior-posterior direction and the medial-lateral direction in both evaluated tasks . We observed significant correlations between balance measures and the following posture evaluation variables : distance between the lower limbs , horizontal alignment of the head and vertical alignment of the head . Our results suggest that posture and balance need to be evaluated for acromegalic patients in clinical practice , as there are significant postural imbalances and deviations in these patients We aim ed to investigate the relationship between postoperative leg length/offset ( LL/OS ) reconstruction and gait performance after total hip arthroplasty ( THA ) . In the course of a prospect i ve r and omized controlled trial , 60 patients with unilateral hip arthrosis received cementless THA through a minimally-invasive anterolateral surgical approach . One year post-operatively , LL and global OS restoration were analyzed and compared to the contralateral hip on AP pelvic radiographs . The combined postoperative limb length/OS reconstruction of the operated hip was categorized as restored ( within 5 mm ) or non-restored ( more than 5 mm reduction or more than 5 mm increment ) . The acetabular component inclination , anteversion and femoral component anteversion were evaluated using CT scans of the pelvis and the femur . 3D gait analysis of the lower extremity and patient related outcome measures ( HHS , HOOS , EQ-5D ) were obtained pre-operatively , six months and twelve months post-operatively by an observer blinded to radiographic results . Component position of cup and stem was comparable between the restored and non-restored group . Combined LL and OS restoration within 5 mm result ed in higher Froude number ( p<0.001 ) , normalized walking speed ( p<0.001 ) and hip range-of-motion ( ROM ) ( p=0.004 ) during gait twelve months postoperatively , whereas gait symmetry was comparable regardless of LL and OS reconstruction at both examinations . Clinical scores did not show any relevant association between the accuracy of LL or OS reconstruction and gait six/twelve months after THA . In summary , postoperative LL/OS discrepancies larger than 5 mm relate to unphysiological gait kinematics within the first year after THA . DRKS00000739 , German Clinical Trials Register Output:	We found most of the published data that we analyzed to be inconsistent , and very little data was obtained on the correlation between LLD severity and changes in body posture stability during st and ing and walking . However , the results of the present review study are in line with previous observational studies , which describe asymmetry in the lower limbs corresponding to biomechanical parameters such as gait kinematics , kinetics , and other parameters described during static ( st and ing ) postural balance .
MS21982	*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 : Most electronic health record ( EHR ) systems have the capability of generating a printed after-visit summary ( AVS ) , but there has been little research on optimal content . We conducted a qualitative study and a r and omized trial to underst and the effect of AVS content on patient recall and satisfaction . Methods : Adult primary care patients ( n = 272 ) with at least 1 chronic condition were r and omly assigned to 4 AVS content conditions : minimum , intermediate , maximum , or st and ard AVS . Demographics and health literacy were measured at an index clinic visit . Recall and satisfaction were measured by telephone 2 days and 2 to 3 weeks after the clinic visit . Results : Average age was 52 years ; 75 % of patients were female , 61 % were Hispanic , and 21 % were African American , and 64 % had adequate health literacy . Average medication recall accuracy was 53 % at 2 days and 52 % at 3 weeks , with no significant difference among groups at either time . Satisfaction with AVS content was high and did not differ among groups . Recall of specific content categories was low and unrelated to group assignment . Health literacy was unrelated to recall and satisfaction . Conclusion : Primary care patients like to receive an AVS , but the amount of information included does not affect content recall or satisfaction with the information OBJECTIVES Diabetes self-management is a key element in the overall management of diabetes . Identifying barriers to disease self-management is a critical step in achieving optimal health outcomes . Our goal was to explore patients ' perceptions about barriers to self-management of diabetes that could possibly help explain poor health outcomes among minority patients . STUDY DESIGN Four focus groups were conducted among 31 predominately African American patients with diabetes who were enrolled in the Baltimore Cardiovascular Partnership Study , a NIH-funded multiyear prospect i ve partnership study . The topic guide consisted of a series of open-ended questions about knowledge of current health status , medication use , continuity of care , blood glucose level and nutrition . RESULTS The focus groups confirmed that previously reported barriers to self-management persisted and identified new concerns that could be associated with poor health outcomes among minority patients with diabetes . Attitudes , perceptions and behaviors surrounding diabetes and self-management of the condition did vary across individuals , however , the variation appeared to reflect the individual 's knowledge and opinions rather than patient 's age , sex , or culture . The primary barrier to diabetes self-management result ed from lack of knowledge of target blood glucose and blood pressure . Several participants found some of the health information to be quite confusing . CONCLUSIONS Diabetes is a major public health concern and the lack of awareness of target blood glucose and blood pressure further complicates the problem . The limited health literacy seen in this study could help explain several of the barriers to self-management . The barriers to self-management identified in this qualitative study are amenable to intervention that could improve health outcomes Introduction Older , chronically ill patients with limited health literacy are often under-engaged in managing their health and turn to the emergency department ( ED ) for healthcare needs . We tested the impact of an ED-initiated coaching intervention on patient engagement and follow-up doctor visits in this high-risk population . We also explored patients ’ care-seeking decisions . Methods We conducted a mixed- methods study including a r and omized controlled trial and in-depth interviews in two EDs in northern Florida . Participants were chronically ill older ED patients with limited health literacy and Medicare as a payer source . Patients were assigned to an evidence -based coaching intervention ( n= 35 ) or usual post-ED care ( n= 34 ) . Qualitative interviews ( n=9 ) explored patients ’ reasons for ED use . We assessed average between-group differences in patient engagement over time with the Patient Activation Measure ( PAM ) tool , using logistic regression and a difference-in-difference approach . Between-group differences in follow-up doctor visits were determined . We analyzed qualitative data using open coding and thematic analysis . Results PAM scores fell in both groups after the ED visit but fell significantly more in “ usual care ” ( average decline −4.64 ) than “ intervention ” participants ( average decline −2.77 ) ( β=1.87 , p=0.043 ) . There were no between-group differences in doctor visits . Patients described well-informed reasons for ED visits including onset and severity of symptoms , lack of timely provider access , and immediate and comprehensive ED care . Conclusion The coaching intervention significantly reduced declines in patient engagement observed after usual post-ED care . Patients reported well-informed reasons for ED use and will likely continue to make ED visits unless strategies , such as ED-initiated coaching , are implemented to help vulnerable patients better manage their health and healthcare Knowledge of nutrition among breast cancer patients is insufficient , despite their motivation to seek valid information about healthy food choices . This study examines the feasibility of nutrition education workshops for cancer survivors , to inform the design of a multi-center intervention . Fifty-nine female English-speaking breast cancer patients , who had completed treatment , were enrolled . Participants were r and omized to the intervention or control group . The intervention group attended six nutrition education sessions , and the control group received brochures . Measurements were done at baseline and 3-month follow-up and included the Assessment Instrument for Breast Cancer ( NLit-BCa ) , fruit/vegetable and general health literacy screeners . Height and weight were measured . Changes in nutrition literacy , health literacy , and food intake from baseline to follow-up ( within-group change ) were calculated for both groups ( effect sizes were reported as Cohen ’s d ) . Participants were mostly white , with a mean age of 58 years , BMI of 31.6 kg/m2 , and had college degrees . Follow-up rates were high ( 89 % = control and 77 % = intervention group ) . At baseline , participants scored high for most NLit-BCa assessment components except food portions in both groups . At the 3-month follow-up , effect sizes ( d ) on the NLit-BCa ranged from −0.5 to 0.16 . The study met its recruitment goals within 6 months . Focus groups indicated that ( a ) attending six sessions was acceptable , ( b ) patients found social/emotional support , ( c ) improvements should include information for special diets and booster sessions . This pilot study suggests that the intervention was acceptable and that scaling up of this intervention is feasible and could provide benefit to breast cancer survivors BACKGROUND Chronic obstructive pulmonary disease ( COPD ) is an illness that affects patients on multiple levels , both physically and psychologically . While there is a growing body of evidence for the efficacy of self-management among patients with COPD , little evidence is available on the optimal content and methods for delivering self-management support . AIMS The purpose of this study was to address gaps in the literature on self-management support by examining patients ' responses to questions about goals , needs , and expectations regarding self-management using qualitative methods in a broadly representative sample of patients with moderate to severe COPD . By focusing on patients ' perceptions of their needs , we hoped to guide development of cognitive-behavioural interventions for self-management support . METHODS Patients > 45 years of age with a physician diagnosis of COPD were recruited as part of a larger r and omised controlled trial design ed to determine the effectiveness of a lifestyle behavioural intervention to increase physical activity . In-depth interviews were conducted at baseline data collection using 10 st and ardised open-ended questions tailored to examine factors relevant to self-management support including concerns , fears , learning needs , barriers , facilitators , and goals . All interviews were audio recorded and analysed using qualitative methods . Responses were coded by three raters into thematic categories . RESULTS A sample of 47 interviews with patients of mean age 68.4 years , 53 % male , 87 % white were used in the analysis . The distribution of spirometric impairment based on percent predicted forced expiratory volume in 1 second ( FEV1 ) was moderate ( 57.5 % ) , severe ( 31.9 % ) , and very severe ( 10.6 % ) . In response to questions targeting needs and goals for care , three main themes ( loss , fear , and desire for improved care ) and seven associated sub-themes were identified . Because of breathlessness and fatigue as well as symptoms from conditions other than COPD , patients reported the loss of ability to participate in pleasurable and necessary activities of daily living and the desire to recover at least some of their functioning . They expressed problems with social isolation and uncertainty about their prognosis , as well as the hope to improve . In addition , fearful experiences associated with uncontrolled breathlessness and a wish for greater underst and ing and knowledge about treatment were major concerns . CONCLUSIONS These qualitative results suggest that the content of self-management support for patients with COPD should focus on addressing patients ' fears associated with the uncertainty , progression , and suffering of their disease , their expectations about overcoming or replacing losses , their needs for improved health literacy and their desire for improved care . These responses indicate areas where cognitive-behavioural intervention should focus in order to enhance patient self-efficacy , motivation , and behavioural change for improved self-management Background : Stroke patients ’ involvement in the rehabilitation process including decision making has made significant advances clinical ly over the past two decades . However , development of patient-focused interventions in stroke rehabilitation is a relatively under developed area of research . The aim of this study was to interpret the explanations that patients gave of their experience after stroke and how these may vali date an already established patient-focused intervention framework – the Quest for quality and improved performance ( QQUIP ) ( 2006 ) that includes seven quality improvement goals . Methods : A r and om purposive sample of eight stroke patients was interviewed between 3 and 6 months following discharge . Patients ’ reports of their experience after stroke were obtained using in-dept semi-structured interviews and analysed using Qualitative Content Analysis . Results : Explanations given by patients included both positive and negative reports of the stroke experience . Regardless of consequences as a result of physical , psychological and social impairments , there were other life style disruptions that were reported by all patients such as taking new medication and adverse effects of these , experiencing increasing fatigue , difficulties with social activities and situations and having to make changes in health behaviours and lifestyle . Some of the core themes that emerged reflected the aims of QQUIP improvement goals that include improving health literacy , clinical decision-making , self-care , patient safety , access to health advice , care experience and service development . Discussion : Further recommendations based on the findings from this study would be to consider using the QQUIP framework for developing intervention studies in stroke rehabilitation care that are person-centred . This framework provides a template that is equipped to address some of the main concerns that people have following the experience of stroke and also focuses on improving quality of care . Implication s for Rehabilitation Consideration for the use of established patient focused frameworks for improving the design and development of rehabilitation stroke interventions . Identify patients ’ main concerns following the experience of stroke and its result ing consequences in developing stroke rehabilitation interventions Greater need to move from a provider-led model of care towards a more favourably balanced view that includes patient participation and involvement in their self management of the rehabilitation programme Output:	Patient perspectives were categorized into four key themes : ( 1 ) Support system ; ( 2 ) Patient self-management ; ( 3 ) Capacities of HCPs ; ( 4 ) Barriers in healthcare systems . " The perspectives of patients with LHL provided valuable input for a comprehensive and person-centred educational framework that can enhance the relevance and quality of education for ( future ) HCPs , and contribute to better person-centred care for patients with LHL
MS21983	*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 Treatment of secondary hyperparathyroidism ( SHPT ) with activated vitamin D analogues is associated with better survival in patients receiving dialysis . It is unclear whether such a benefit is present in patients with predialysis chronic kidney disease ( CKD ) . METHODS We examined the association of oral calcitriol treatment with mortality and the incidence of dialysis in 520 male US veterans ( mean [ SD ] age , 69.8 [ 10.3 ] years ; 23.5 % black ) with CKD stages 3 to 5 and not yet receiving dialysis ( mean [ SD ] estimated glomerular filtration rate , 30.8 [ 11.3 ] ) . Associations were examined by the Kaplan-Meier method and in Poisson regression models with adjustment for age , race , comorbidities , smoking , blood pressure , body mass index , use of phosphate binders , estimated glomerular filtration rate , proteinuria , white blood cell count , percentage of lymphocytes , and levels of parathyroid hormone , calcium , phosphorus , albumin , bicarbonate , and hemoglobin . RESULTS Two hundred fifty-eight of 520 subjects received treatment with calcitriol , 0.25 to 0.5 microg/d , for a median duration of 2.1 years ( range , 0.06 - 6.0 years ) . The incidence rate ratios for mortality and combined death and dialysis initiation were significantly lower in treated vs untreated patients ( P < .001 for both in the fully adjusted models ) . Treatment with calcitriol was associated with a trend toward a lower incidence of dialysis . These results were consistent across different subgroups . CONCLUSIONS Treatment with the activated vitamin D analogue calcitriol appears to be associated with significantly greater survival in patients with CKD not yet receiving dialysis . R and omized clinical trials are required to verify the causality of these associations and to examine whether similar associations are seen with different activated vitamin D analogues BACKGROUND A need exists for a therapy that lowers parathyroid hormone ( PTH ) without increasing calcium x phosphorus in patients with secondary hyperparathyroidism . The calcimimetic AMG 073 increases the sensitivity of the parathyroid calcium-sensing receptor to extracellular calcium , thereby reducing PTH secretion . Consequently , AMG 073 may provide a novel therapy for secondary hyperparathyroidism . METHODS Seventy-eight hemodialysis patients with secondary hyperparathyroidism were enrolled into this 18-week , double-blind , r and omized , placebo-controlled , dose titration study . Daily oral AMG 073 doses were administered to determine the effect on PTH , serum calcium , phosphorus , and calcium x phosphorus . RESULTS The mean baseline PTH was similar in patients administered AMG 073 or placebo ( 632 + /- 280.1 pg/mL vs. 637 + /- 455.9 pg/mL , respectively ) . PTH decreased by 26.0 % in the AMG 073-treated group , compared with an increase of 22.0 % in the placebo group ( P < 0.001 ) . A greater proportion in the AMG 073 group ( 38 % ) had a decrease in PTH > or=30 % , compared with the placebo group ( 8 % ) ( P = 0.001 ) . Decreases in PTH were independent of baseline vitamin D usage . Patients receiving AMG 073 had an 11.9 % decrease in calcium x phosphorus compared with a 10.9 % increase in the placebo group ( P < 0.001 ) . Use of vitamin D sterols , as well as both calcium and noncalcium-containing phosphate binders . were similar between treatment groups . Administration of AMG 073 was safe and well tolerated in this 18-week study . CONCLUSIONS The calcimimetic AMG 073 decreases both PTH and calcium x phosphorus levels in hemodialysis patients with secondary hyperparathyroidism Management of secondary hyperparathyroidism is challenging with traditional therapy . The calcimimetic cinacalcet HCl acts on the calcium-sensing receptor to increase its sensitivity to calcium , thereby reducing parathyroid hormone ( PTH ) secretion . This phase 3 , multicenter , r and omized , placebo-controlled , double-blind study evaluated the efficacy and safety of cinacalcet in hemodialysis ( HD ) and peritoneal dialysis ( PD ) patients with PTH > or = 300 pg/ml despite traditional therapy . A total of 395 patients received once-daily oral cinacalcet ( 260 HD , 34 PD ) or placebo ( 89 HD , 12 PD ) titrated from 30 to 180 mg to achieve a target intact PTH ( iPTH ) level of < or = 250 pg/ml . During a 10-wk efficacy assessment phase , cinacalcet was more effective than control for PTH reduction outcomes , including proportion of patients with mean iPTH levels < or = 300 pg/ml ( 46 versus 9 % ) , proportion of patients with > or = 30 % reduction in iPTH from baseline ( 65 versus 13 % ) , and proportion of patients with > or = 20 , > or = 40 , or > or = 50 % reduction from baseline . Cinacalcet had comparable efficacy in HD and PD patients ; 50 % of PD patients achieved a mean iPTH < or = 300 pg/ml . Cinacalcet also significantly reduced serum calcium , phosphorus , and Ca x P levels compared with control treatment . The most common side effects , nausea and vomiting , were usually mild to moderate in severity and transient . Once-daily oral cinacalcet was effective in rapidly and safely reducing PTH , Ca x P , calcium , and phosphorus levels in patients who received HD or PD . Cinacalcet offers a new therapeutic option for controlling secondary hyperparathyroidism in patients with chronic kidney disease on dialysis BACKGROUND The calcimimetic agent R-568 lowers plasma parathyroid hormone ( PTH ) levels in hemodialysis patients with mild secondary hyperparathyroidism , but its efficacy in those with more severe secondary hyperparathyroidism has not been studied . METHODS Twenty-one patients undergoing hemodialysis three times per week with plasma PTH levels between 300 and 1200 pg/mL were r and omly assigned to 15 days of treatment with either 100 mg of R-568 ( N = 16 ) or placebo ( N = 5 ) . Plasma PTH and blood ionized calcium levels were measured at intervals of up to 24 hours after oral doses on days 1 , 2 , 3 , 5 , 8 , 11 , 12 , and 15 . RESULTS Pretreatment PTH levels were 599 + /- 105 ( mean + /- SE ) and 600 + /- 90 pg/mL in subjects given R-568 or placebo , respectively , and values on the first day of treatment did not change in those given placebo . In contrast , PTH levels fell by 66 + /- 5 % , 78 + /- 3 % , and 70 + /- 3 % at one , two , and four hours , respectively , after initial doses of R-568 , remaining below pretreatment values for 24 hours . Blood ionized calcium levels also decreased after the first dose of R-568 but did not change in patients given placebo . Despite lower ionized calcium concentrations on both the second and third days of treatment , predose PTH levels were 422 + /- 70 and 443 + /- 105 pg/mL , respectively , in patients given R-568 , and values fell each day by more than 50 % two hours after drug administration . Predose PTH levels declined progressively over the first nine days of treatment with R-568 and remained below pretreatment levels for the duration of study . Serum total and blood ionized calcium concentrations decreased from pretreatment levels in patients given R-568 , whereas values were unchanged in those given placebo . Blood ionized calcium levels fell below 1.0 mmol/L in 7 of 16 patients receiving R-568 ; five patients withdrew from study after developing symptoms of hypocalcemia , whereas three completed treatment after the dose of R-568 was reduced . CONCLUSIONS The calcimimetic R-568 rapidly and markedly lowers plasma PTH levels in patients with secondary hyperparathyroidism caused by end-stage renal disease BACKGROUND This prospect i ve , r and omized , controlled trial compared the progression of vascular and cardiac valve calcification in 360 prevalent adult hemodialysis patients with secondary hyperparathyroidism treated with either cinacalcet plus low-dose vitamin D sterols or flexible doses of vitamin D sterols alone . METHODS Eligible subjects were on hemodialysis for ≥ 3 months with parathyroid hormone ( PTH ) > 300 pg/mL or PTH 150 - 300 pg/mL with calcium-phosphorus product > 50 mg(2)/dL(2 ) while receiving vitamin D. All subjects received calcium-based phosphate binders . Coronary artery calcification ( CAC ) and aorta and cardiac valve calcium scores were determined both by Agatston and volume scoring using multi-detector computed tomography . Subjects with Agatston CAC scores ≥ 30 were r and omized to cinacalcet ( 30- 180 mg/day ) plus low-dose calcitriol or vitamin D analog ( ≤ 2 μg paricalcitol equivalent/dialysis ) , or flexible vitamin D therapy . The primary end point was percentage change in Agatston CAC score from baseline to Week 52 . RESULTS Median ( P10 , P90 ) Agatston CAC scores increased 24 % ( -22 % , 119 % ) in the cinacalcet group and 31 % ( -9 % , 179 % ) in the flexible vitamin D group ( P = 0.073 ) . Corresponding changes in volume CAC scores were 22 % ( -12 % , 105 % ) and 30 % ( -6 % , 133 % ; P = 0.009 ) . Increases in calcification scores were consistently less in the aorta , aortic valve and mitral valve among subjects treated with cinacalcet plus low-dose vitamin D sterols , and the differences between groups were significant at the aortic valve . CONCLUSIONS In hemodialysis patients with moderate to severe secondary hyperparathyroidism , cinacalcet plus low-dose vitamin D sterols may attenuate vascular and cardiac valve calcification BACKGROUND AND OBJECTIVES Patients with chronic kidney disease ( CKD ) receiving dialysis often develop secondary hyperparathyroidism with disturbed calcium and phosphorus metabolism . The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative ( KDOQI ) was established to guide treatment practice s for these disorders . The ACHIEVE study was design ed to test two treatment strategies for achieving KDOQI goals . DESIGN , SETTING , PARTICIPANTS , MEASUREMENTS Individuals on hemodialysis treated with vitamin D sterols were enrolled in this 33-week study . Subjects were r and omly assigned to treatment with either cinacalcet and low-dose vitamin D ( Cinacalcet-D ) or flexible vitamin D alone ( Flex-D ) to achieve KDOQI-recommended bone mineral targets . ACHIEVE included a 6-week screening phase , including vitamin D washout , a 16-week dose-titration phase , and an 11-week assessment phase . RESULTS Of 173 subjects enrolled , 83 % of Cinacalcet-D and 67 % of Flex-D subjects completed the study . A greater proportion of Cinacalcet-D versus Flex-D subjects had a > 30 % reduction in parathyroid hormone ( PTH ) ( 68 % versus 36 % , P < 0.001 ) as well as PTH < 300 pg/ml ( 44 % versus 23 % , P = 0.006 ) . The proportion of subjects simultaneously achieving targets for intact PTH ( 150 - 300 pg/ml ) and calcium-phosphorus product ( Ca x P ) ( < 55 mg2/dl2 ) was also greater ( 21 % versus 14 % ) , but this was not statistically significant . This was attributable to 19 % of Cinacalcet-D subjects with a PTH value below the KDOQI target range . CONCLUSIONS Achievement of KDOQI targets was difficult , especially with Flex-D. Maintaining calcium and phosphorus target values precluded the use of vitamin D doses necessary to lower PTH to within the narrow target range and highlighted limitations inherent to the KDOQI treatment algorithm BACKGROUND Secondary hyperparathyroidism is observed in patients with early chronic kidney disease ( CKD ) . This study investigated the safety and efficacy of cinacalcet for secondary hyperparathyroidism in participants with CKD not receiving dialysis . STUDY DESIGN Double-blind , r and omized , 32-week , phase 3 study . SETTING & PARTICIPANTS 404 participants with stage 3 or 4 Output:	Cinacalcet reduces the need for parathyroidectomy in patients with CKD stage 5D , but does not appear to improve all-cause or cardiovascular mortality . Additional trials in CKD stage 5D are unlikely to change our confidence in the treatment effects of cinacalcet in this population
MS21984	*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 Owing to modern lifestyles , individuals are dependent on out-of-home eating . The catering sector can have a pivotal role in influencing our food choices . The objective of the present study was to examine the impact of a structured catering initiative on food choices in a public sector workplace setting . DESIGN A cross-sectional comparison study in two hospitals , one of which had implemented a catering initiative design ed to provide nutritious food while reducing sugar , fat and salt intakes . SETTING Two public sector hospitals in Cork , Irel and . SUBJECTS A total of 100 r and om participants aged 18 - 64 years ( fifty intervention , fifty non-intervention ) who consumed at least one main meal in the hospital staff canteen daily . Each respondent was asked to complete one anonymous 24 h dietary recall and question naire . Food and nutrient analysis was conducted using WISP ( Weighed Intake Software Program ) . RESULTS Reported mean intakes of total sugars ( P < 0·001 ) , total fat ( P < 0·000 ) , saturated fat ( P < 0·000 ) and salt ( P < 0·046 ) were significantly lower in the intervention hospital when adjusted for age and gender . In the intervention hospital , 72 % of respondents , compared with 42 % in the non-intervention hospital , complied with the recommended under-3 daily servings of food high in fat and sugar ( P < 0·005 ) . In the intervention hospital , 43 % of respondents exceeded the recommended salt intake of 4 - 6 g/d , compared with 57 % in the non-intervention hospital . CONCLUSIONS Structured catering initiatives in the workplace are a potentially important option in the promotion of healthy food choices . Targeted public health programmes and health policy changes are needed to motivate caterers in the public sector and other industries to develop interventions that promote a healthy diet OBJECTIVE To assess the impact of a school-based nutrition education intervention aim ed at increasing the consumption of fruits and vegetables . DESIGN The intervention programme increased the provision of fruits and vegetables in schools and provided a range of point-of-purchase marketing material s , newsletters for children and parents , and teacher information . Curriculum material s at age 6 - 7 and 10 - 11 years were also developed and utilised . Evaluation was undertaken with groups of younger ( aged 6 - 7 years ) and older ( aged 10 - 11 years ) children . Methods included 3-day dietary records with interview and cognitive and attitudinal measures at baseline , with follow-up at 9 months , in intervention and control schools . SETTING The work was undertaken in primary schools in Dundee , Scotl and . SUBJECTS Subjects comprised 511 children in two intervention schools with a further 464 children from two schools acting as controls . RESULTS Children ( n=64 ) in the intervention schools had an average increase in fruit intake ( 133+/-1.9 to 183+/-17.0 g day(-1 ) ) that was significantly ( P<0.05 ) greater than the increase ( 100+/-11.7 to 107+/-14.2 g day(-1 ) ) estimated in children ( n=65 ) in control schools . No other changes in food or nutrient intake were detected . Increases in scores for variables relating to knowledge about fruits and vegetables and subjective norms were also greater in the intervention than in the control group , although taste preferences for fruits and vegetables were unchanged . CONCLUSIONS It is concluded that a whole school approach to increasing intakes of fruits and vegetables has a modest but significant effect on cognitive and attitudinal variables and on fruit intake The S and y Lake school-based diabetes prevention program is a culturally appropriate intervention for Ojibway-Cree students in the 3rd , 4th , and 5th grade s. This paper reports the results of the program in changing dietary intake behaviors and related psychosocial factors . Physical activity results are not included . The study was a pretest/post-test , single- sample design conducted during the 1998 - 1999 school year . A total of 122 students completed all 4 measurements ( anthropometry , 24-h dietary recall , and 2 question naires ) , at baseline and follow-up . There were significant increases ( P < 0.0001 ) in dietary intention , dietary preference , knowledge , and dietary self-efficacy , and in the curriculum knowledge scale between baseline and follow-up . Intervention exposure was significantly associated with being in the highest category for knowledge about foods that were low in dietary fat [ Medium Exposure odds ratio ( OR ) : 3.4 ; P < 0.05 ; High Exposure OR : 6.4 ; P < 0.05 ] , being in the highest category for dietary self-efficacy ( Medium Exposure OR : 3.7 ; P < 0.05 ; High Exposure OR : 3.9 ; P < 0.1 ) , being in the highest category for knowledge about curriculum concepts ( Medium Exposure OR : 3.4 ; P < 0.05 ; High Exposure OR : 9.4 : P < 0.01 ) , and for having met the age + 5 g dietary fiber intake/d ( Medium Exposure OR : 2.9 ; P < 0.1 ; High Exposure OR : 11.0 ; P < 0.01 ) . Exposure to the intervention was not associated with dietary intent or the percentage of energy from dietary fat . This program was associated with improved knowledge and the psychosocial factors related to healthy eating and dietary fiber intake of students in a remote First Nations community BACKGROUND This study evaluated the effects of a school-based dietary intervention program to increase fruit and vegetable consumption among fourth- grade rs . METHODS Twenty-eight elementary schools were r and omized to an immediate intervention condition or to a delayed intervention control condition . Measures of diet and psychosocial variables were collected at base line and 1 and 2 years post-baseline . The intervention included classroom , parent , and cafeteria components . RESULTS Mean daily consumption of fruit and vegetables was higher for the intervention children compared with controls at Follow-up 1 ( X(t ) = 3.96 , X(c ) = 2.28 ) and at Follow-up 2 ( X(t ) = 3.20 , X(c ) = 2.21 ) . Macro- and micronutrient changes favoring the intervention children were also observed at both Follow-up 1 and Follow-up 2 . Mean daily consumption of fruit and vegetables was higher for intervention parents compared with controls at Follow-up 1 ( X(t ) = 4.23,X(c ) = 3.94 ) but not at Follow-up 2 . CONCLUSIONS Strong effects were found for the High 5 intervention on fruit and vegetable consumption , on macro- and micro-nutrients , and on psychosocial variables . Future work is needed to enhance the intervention effects on parents ' consumption and to test the effectiveness of the intervention when delivered by classroom teachers OBJECTIVES This study examined the effects of pricing and promotion strategies on purchases of low-fat snacks from vending machines . METHODS Low-fat snacks were added to 55 vending machines in a convenience sample of 12 secondary schools and 12 worksites . Four pricing levels ( equal price , 10 % reduction , 25 % reduction , 50 % reduction ) and 3 promotional conditions ( none , low-fat label , low-fat label plus promotional sign ) were crossed in a Latin square design . Sales of low-fat vending snacks were measured continuously for the 12-month intervention . RESULTS Price reductions of 10 % , 25 % , and 50 % on low-fat snacks were associated with significant increases in low-fat snack sales ; percentages of low-fat snack sales increased by 9 % , 39 % , and 93 % , respectively . Promotional signage was independently but weakly associated with increases in low-fat snack sales . Average profits per machine were not affected by the vending interventions . CONCLUSIONS Reducing relative prices on low-fat snacks was effective in promoting lower-fat snack purchases from vending machines in both adult and adolescent population OBJECTIVES A r and omized school based trial sought to increase fruit and vegetable consumption among children using a multicomponent approach . METHODS The intervention , conducted in 20 elementary schools in St. Paul , targeted a multiethnic group of children who were in the fourth grade in spring 1995 and the fifth grade in fall 1995 . The intervention consisted of behavioral curricula in classrooms , parental involvement , school food service changes , and industry support and involvement . Lunchroom observations and 24-hour food recalls measured food consumption . Parent telephone surveys and a health behavior question naire measured psychosocial factors . RESULTS The intervention increased lunchtime fruit consumption and combined fruit and vegetable consumption , lunchtime vegetable consumption among girls , and daily fruit consumption as well as the proportion of total daily calories attributable to fruits and vegetables . CONCLUSIONS Multicomponent school-based programs can increase fruit and vegetable consumption among children . Greater involvement of parents and more attention to increasing vegetable consumption , especially among boys , remain challenges in future intervention research OBJECTIVES We evaluated an environmental intervention intended to increase sales of lower-fat foods in secondary school cafeterias . METHODS Twenty secondary schools were r and omly assigned to either an environmental intervention or a control group for a 2-year period . The intervention increased the availability of lower-fat foods and implemented student-based promotions . RESULTS A steeper rate of increase in sales of lower-fat foods in year 1 ( 10 % intervention vs -2.8 % control , P = .002 ) and a higher percentage of sales of lower-fat foods in year 2 ( 33.6 % intervention vs 22.1 % control , P = .04 ) were observed . There were no significant changes in student self-reported food choices . CONCLUSIONS School-based environmental interventions to increase availability and promotion of lower-fat foods can increase purchase of these foods among adolescents BACKGROUND 5 a Day for Better Health is a simple message encouraging people to eat more fruits and vegetables . The Seattle 5 a Day worksite investigators design ed and evaluated an intervention , organized on stages of behavioral change , to increase worksitewide fruit and vegetable consumption . METHODS We recruited 28 worksites with cafeterias and r and omized 14 to intervention and 14 to control . The intervention addressed both changes in the work environment and individual level behavior change . In each worksite , an employee advisory board , with study interventionist assistance , implemented the program . By surveying cross-sectional sample s of 125 employees per worksite , we compared worksite mean fruit and vegetable consumption at 2-year follow-up with that at baseline . Unobtrusive site-level indicators including plate observation and cafeteria checklist were also used . RESULTS The difference at 2 years was 0.5 for the intervention worksites and 0.2 for the control worksites , with an intervention effect of 0.3 daily serving ( P < 0.05 ) . Other measures of fruit and vegetable consumption , including unobtrusive indicators , supported the effectiveness of the intervention . CONCLUSIONS This simple 5 a Day intervention is feasible and acceptable for use in worksites with cafeterias . There was a significant differential increase in fruit and vegetable consumption in the intervention worksites . This kind of worksite intervention can achieve important health benefits on a population basis , because of its potential to reach large numbers of people The Cafeteria Power Plus project examined whether a cafeteria-based intervention would increase the fruit and vegetable ( FV ) consumption of children . Twenty-six schools were r and omly assigned to either an intervention or control condition . Baseline lunch observations of a sample ( N = 1668 ) of first- and third- grade students occurred in the spring of 2000 ; follow-up was in the spring of 2002 . The intervention took place during two consecutive school years beginning in the fall of 2000 and consisted of daily activities ( increasing the availability , attractiveness , and encouragement for FV ) and special events ( kick-offs , samplings , challenge weeks , theater production , and finale meal ) . Training of food-service staff and cook managers was ongoing throughout the intervention phase . Students in the intervention schools significantly increased their total fruit intake . Process measures indicated that verbal encouragement by food-service staff was associated with outcomes . The outcomes suggest that multicomponent interventions are more powerful than cafeteria programs alone with this age group OBJECTIVE A two-phase study was conducted to determine the effect of an environmental intervention aim ed to increase the selection of low- and moderate-fat entrees at school . DESIGN An evaluation of a school-wide intervention followed for two semesters . SUBJECTS Two schools of similar size and demographic data were r and omly assigned to either intervention or control . Participants were the children in these schools . INTERVENTION In Phase 1 , the rotation of existing entrees was modified such that one of three entree choices was low or moderate in fat . In Phase 2 , the number of competing high-fat entrees was reduced from two choices to one . MAIN OUTCOME MEASURES Data were : ( a ) entree fat content ( determined by a registered dietitian ) and ( b ) the aggregate entree selection s compiled from daily selection reports . STATISTICAL ANALYSES PERFORMED Frequency distributions were used to describe entree availability . Two-way analysis of variance indicated differences in the mean daily selection of low- , moderate- , and high-fat entrees . RESULTS In Phase 1 in the intervention school , the number of days that a low-fat entree was offered increased by 70 % , with no increase in the rate of selection of the low- or moderate-fat entrees . In Phase 2 Output:	Implementation of healthy food procurement policies in schools , worksites , hospitals , care homes , correctional facilities , government institutions , and remote communities increase markers of healthy eating .
MS21985	*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 assess in a prospect i ve trial the feasibility and late toxicity of hypofractionated radiotherapy ( RT ) for prostate cancer . METHODS AND MATERIAL S Eligible patients had clinical stage T1c-2cNXM0 disease . They received 60 Gy in 20 fractions over 4 weeks with intensity-modulated radiotherapy including daily on-line image guidance with intraprostatic fiducial markers . RESULTS Between June 2001 and March 2004 , 92 patients were treated with hypofractionated RT . The cohort had a median prostate-specific antigen value of 7.06 ng/mL. The majority had Gleason grade 5 - 6 ( 38 % ) or 7 ( 59 % ) disease , and 82 patients had T1c-T2a clinical staging . Overall , 29 patients had low-risk , 56 intermediate-risk , and 7 high-risk disease . Severe acute toxicity ( Grade 3 - 4 ) was rare , occurring in only 1 patient . Median follow-up was 38 months . According to the Phoenix definition for biochemical failure , the rate of biochemical control at 14 months was 97 % . According to the previous American Society for Therapeutic Radiology and Oncology definition , biochemical control at 3 years was 76 % . The incidence of late toxicity was low , with no severe ( Grade > or =3 ) toxicity at the most recent assessment . CONCLUSIONS Hypofractionated RT using 60 Gy in 20 fractions over 4 weeks with image guidance is feasible and is associated with low rates of late bladder and rectal toxicity . At early follow-up , biochemical outcome is comparable to that reported for conventionally fractionated controls . The findings are being tested in an ongoing , multicenter , Phase III trial PURPOSE To perform a r and omized trial comparing 70 and 80 Gy radiotherapy for prostate cancer . PATIENTS AND METHODS A total of 306 patients with localized prostate cancer were r and omized . No and rogen deprivation was allowed . The primary endpoint was biochemical relapse according to the modified 1997-American Society for Therapeutic Radiology and Oncology and Phoenix definitions . Toxicity was grade d using the Radiation Therapy Oncology Group 1991 criteria and the late effects on normal tissues-subjective , objective , management , analytic scales ( LENT-SOMA ) scales . The patients ' quality of life was scored using the European Organization for Research and Treatment of Cancer Quality of Life Question naire 30-item cancer-specific and 25-item prostate-specific modules . RESULTS The median follow-up was 61 months . According to the 1997-American Society for Therapeutic Radiology and Oncology definition , the 5-year biochemical relapse rate was 39 % and 28 % in the 70- and 80-Gy arms , respectively ( p = .036 ) . Using the Phoenix definition , the 5-year biochemical relapse rate was 32 % and 23.5 % , respectively ( p = .09 ) . The subgroup analysis showed a better biochemical outcome for the higher dose group with an initial prostate-specific antigen level > 15 ng/mL. At the last follow-up date , 26 patients had died , 10 of their disease and none of toxicity , with no differences between the two arms . According to the Radiation Therapy Oncology Group scale , the Grade 2 or greater rectal toxicity rate was 14 % and 19.5 % for the 70- and 80-Gy arms ( p = .22 ) , respectively . The Grade 2 or greater urinary toxicity was 10 % at 70 Gy and 17.5 % at 80 Gy ( p = .046 ) . Similar results were observed using the LENT-SOMA scale . Bladder toxicity was more frequent at 80 Gy than at 70 Gy ( p = .039 ) . The quality -of-life question naire results before and 5 years after treatment were available for 103 patients with no differences found between the 70- and 80-Gy arms . CONCLUSION High-dose radiotherapy provided a better 5-year biochemical outcome with slightly greater toxicity BACKGROUND / AIM Based on a radiobiological assumption of a low alpha/beta ( α/β ) ratio for prostate cancer , hypofractionated radiotherapy has increasingly gained traction in the clinical practice and recent guidelines have confirmed the non-inferiority of this approach . Nevertheless , the largest studies that have used hypofractionation so far , employed image-guided radiation therapy/intensity modulated radiation therapy ( IGRT/IMRT ) facilities that might have overcome the radiobiological advantages , which remain to be fully confirmed . The aim of this trial was to evaluate the feasibility of a hypofractionated schedule delivered with 3D-Conformal Radiotherapy to prostate and seminal vesicles in combination with hormonal therapy . PATIENTS AND METHODS The study included 97 consecutive patients with localized prostate cancer ( PCa ) , irrespective of risk class , treated with a schedule of 62 Gy in 20 fractions over 5 weeks ( 4 fractions of 3.1 Gy each per week ) . According to National Comprehensive Cancer Network ( NCCN ) prognostic classification , patients were divided into a favourable group ( 19 % ) , intermediate group ( 41 % ) and unfavourable group ( 40 % ) . Early and late toxicities were scored using the radiation toxicity grading/European Organisation for Research and Treatment of Cancer ( RTOG/EORTC ) criteria . Additionally , the international prostate symptom index ( IPSS ) for benign prostate hypertrophy was used to evaluate obstructive urinary symptoms . Biochemical outcome was reported according to the Phoenix definition for biochemical failure . Hormonal therapy ( HT ) was administrated in 92 % of patients . RESULTS After a median follow-up of 39 months ( range=25 - 52 ) , maximum ≥G2 late genitourinary ( GU ) and gastrointestinal ( GI ) toxicities occurred in 8 % and 11 % patients , respectively . The corresponding figures for acute toxicities were 24 % and 15 % . Patients with higher IPSS score before enrolment had significantly worse urinary function after treatment . Only 2 % of patients died from PCa . Biochemical non- evidence of disease ( bNED ) was 83 % for all patients . CONCLUSION Our study confirms that 3D conformal radiotherapy ( 3DCRT ) remains a safe and effective method to deliver a dose-escalated hypofractionated regimen for PCa patients in all risk classes with acceptable toxicity rates and optimal biochemical control Background Quality of life ( QoL ) is one of the most significant issues in prostate cancer treatment decisions . This study aim ed to investigate the toxicity of hypofractionated stereotactic radiotherapy ( SBRT ) and QoL after treatment in localized prostate cancer patients . Material s and methods A prospect i ve single-center clinical study was performed in low- and intermediate-risk prostate cancer patients . Patients received 33.5 Gy in 5 fractions ( SHARP regimen ) . Acute and late toxicity was assessed according to RTOG/EORTC score . Patients filled out EORTC QLQ-C30 and prostate cancer-specific QLQ-PR25 question naires . Results The analysis included 68 prostate cancer patients ( 55–83 years , median 73 ) with clinical stage T1c-T2cN0M0 , median combined Gleason score of 6 ( 3–8 ) , and median prostate-specific antigen ( PSA ) level of 10 ng/mL ( 4–20 ng/mL ) . Neoadjuvant and rogen deprivation therapy was given to 52 patients ( 76.5 % ) , and stopped in 31 patients ( 45.5 % ) after 6 months ; in 21 patients ( 31 % ) after 2–3 years . Average and median follow-up was 24 months ( 18–45 ) . Median nadir PSA level was 0.03 ng/mL for all patients and 0.6 ng/mL for patients without hormone treatment . No patients had PSA failure . There were no acute grade IV toxicities . One patient ( 1.5 % ) developed grade III and 24 patients ( 35.3 % ) grade II acute bladder toxicity . No one developed grade III and 7 patients ( 10.3 % ) grade II acute rectal toxicity . No grade III or IV late gastrointestinal or genitourinary toxicities were reported . Grade II late urinary symptoms were observed in 8 patients ( 11.8 % ) and gastrointestinal symptoms in 3 patients ( 4.4 % ) . Global health status/QoL was good and improved during the observational period . ConclusionS BRT for prostate cancer patients is a well-tolerated treatment in terms of toxicity and QoL , has no negative impact on functioning and everyday life , with the important benefit of a short treatment period . However , long-term follow-up data are needed . ZusammenfassungHintergrundDie Lebensqualität ( QoL ) ist zu einem der wichtigsten Schwerpunkte bei der Wahl der Prostatakarzinombeh and lung geworden . Das Thema dieser Studie war die Untersuchung der Toxizität der hypofraktionierten stereotaktischen Radiotherapie ( SBRT ) und der QoL nach Beh and lung des lokal begrenzten Prostatakarzinoms . Material ien und Method enDie prospektive , monozentrische , klinische Studie wurde bei Prostatakarzinompatienten mit niedrigem bis mittlerem Risiko durchgeführt . Die Patienten erhielten 33,5 Gy in 5 Fraktionen ( SHARP-Beh and lungsschema ) . Akute und späte Toxizität wurden nach den Kriterien des RTOG/EORTC-Scores klassifiziert . Die Patienten füllten das EORTC-QLQ-C30- und das prostatakarzinomspezifische QLQ-PR25-Formular aus . ErgebnisseDie Analyse umfasste 68 Prostatakarzinompatienten ( medianes Alter 73 , Spanne 55–83 Jahre ) i m klinischen Staging T1c – T2cN0M0 , mit einem medianen Gleason-Score von 6 ( Spanne 3–8 ) und einem medianen PSA-Wert ( prostataspezifisches Antigen ) von 10 ng/ml ( Spanne 4–20 ng/ml ) . Eine neoadjuvante And rogendeprivationstherapie erhielten 52 Patienten ( 76,5 % ) ; die Hormontherapie beendet 31 Patienten ( 45,5 % ) nach 6 Monaten und 21 Patienten ( 31 % ) nach 2–3 Jahren . Das durchschnittliche und mediane Follow-up dauerte 24 Monate ( Spanne 18–45 ) . Der mediane PSA-Nadir betrug 0,03 ng/ml für alle Patienten und 0,6 ng/ml für Patienten ohne Hormontherapie . PSA-Versagen und akute Grad-IV-Toxizitäten traten nicht auf . Ein Patient ( 1,5 % ) hatte eine Grad-III- und 24 Patienten ( 35,3 % ) eine Grad-II-Harnblasentoxizität , kein Patient eine Grad-III- und 7 Patienten ( 10,3 % ) eine akute Grad-II-Rektumtoxizität . Späte gastrointestinale oder urogenitale Toxizitäten III . oder IV . Grade s wurden nicht berichtet . Bei 8 Patienten ( 11,8 % ) traten späte Miktionsbeschwerden II . Grade s und bei 3 Patienten ( 4,4 % ) gastrointestinale Symptome auf . Globaler Gesundheitsstatus/QoL war gut und besserte sich in der untersuchten Zeit . SchlussfolgerungSBRT ist beim Prostatakarzinom eine gut tolerierte Beh and lung hinsichtlich Toxizität und QoL , ohne negativen Einfluss auf das Alltagsleben und dem wichtigen Vorteil einer kurzen Beh and lungszeit . Langfristige Follow-up-Untersuchungen müssen noch folgen Summary Background Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment . We present a pre-planned analysis of the efficacy and side-effects of a r and omised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up . Methods CHHiP is a r and omised , phase 3 , non-inferiority trial that recruited men with localised prostate cancer ( pT1b – T3aN0M0 ) . Patients were r and omly assigned ( 1:1:1 ) to conventional ( 74 Gy delivered in 37 fractions over 7·4 weeks ) or one of two hypofractionated schedules ( 60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3·8 weeks ) all delivered with intensity-modulated techniques . Most patients were given radiotherapy with 3–6 months of neoadjuvant and concurrent and rogen suppression . R and omisation was by computer-generated r and om permuted blocks , stratified by National Comprehensive Cancer Network ( NCCN ) risk group and radiotherapy treatment centre , and treatment allocation was not masked . The primary endpoint was time to biochemical or clinical failure ; the critical hazard ratio ( HR ) for non-inferiority was 1·208 . Analysis was by intention to treat . Long-term follow-up continues . The CHHiP trial is registered as an International St and ard R and om Output:	RESULTS The initial search yielded 575 results , but only 32 manuscripts met all eligibility requirements : in terms of radiation-induced side effects , such as gastrointestinal and genitourinary acute and late toxicity , hypofractionated 3DCRT seemed to be more advantageous than 3DCRT with conventional fractionation as well as IMRT with conventional fractionation compared to 3DCRT with conventional fractionation ; furthermore , IMRT hypofractionated technique appeared more advantageous than IMRT with conventional fractionation in late toxicities . R and omized trials meta- analysis disclosed an advantage in terms of acute gastrointestinal and late genitourinary toxicity for Hypofractionated schemes .
MS21986	*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: Although the incidence of carotid atheromatous disease is presumably equal between the right and left carotid arteries , right and left carotid endarterectomies ( CEs ) may not be performed with equal frequency on the two sides . This study sought to examine whether right and left CEs are performed with equal frequency and whether there are any differences in outcome between these groups . Detailed chart review was performed on all CEs performed from 1979 through 1998 at our institution , and those lacking side data were excluded . Data were collected on the side of the procedure , demographics , comorbid conditions , details of the procedure , hospital stay , and major complications . The surgeons performing CE were surveyed about their practice of considering side factors . CE was performed on the left in 1190 ( 52 % ) of 2305 procedures ; 1115 ( 48 % ) of the procedures were right CEs . This difference is statistically significant ( P = 0.014 ) . No significant differences in demographics , comorbidity , presence of symptoms before surgery , length of stay , or postoperative morbidity or mortality between the left and right groups were found . A majority of the surgeons surveyed indicated they do consider the relationship of side of the carotid disease to the patient 's dominant side . The significant difference in the performance of left CE more often than right has not been previously reported . This may reflect willingness by surgeons to intervene more frequently in carotid disease on the side supplying the dominant hemisphere . A prospect i ve CE outcome study that identifies the side of CE and the patient 's dominant side is needed for further exploration of this issue BACKGROUND The objective of this study was to assess whether carotid endarterectomy is an appropriate treatment for patients with recent cerebrovascular events in the territory supplied by a moderately stenosed ( 30 - 69 % ) internal carotid artery . Results have previously been reported for severe ( 70 - 99 % ) and mild ( 0 - 29 % ) stenosis . METHODS A multicentre r and omised controlled trial recruited 1599 patients with moderate stenosis treated in 97 hospitals from 15 countries . 60 % of patients were allocated to receive and 40 % to avoid carotid endarterectomy . The analysis was by intention to treat . FINDINGS Nine patients were omitted from the analysis because no follow-up data were received . Stroke-free life expectancy ( curtailed at 8 years ) was shorter in the surgery patients than in the non-surgery control groups ( patients with 30 - 49 % stenosis , life expectancy = 6.16 years [ controls : 6.63 years ] ; patients with 50 - 69 % stenosis , life expectancy = 5.93 [ 6.14 ] years ) . It remains possible that patients might derive some benefit from surgery in the very long term ; however , our data show that no benefit would be gained over a period of < 4 - 5 years in patients with 50 - 69 % stenosis and < 6 - 7 years in patients with 30 - 49 % stenosis . INTERPRETATION Previous interim results from this study showed that surgery is beneficial in patients with severe stenosis but harmful in those with mild stenosis . With more r and omised patients and longer follow-up , the study now shows that endarterectomy is not indicated for most , possibly all , patients with moderate symptomatic carotid stenosis BACKGROUND AND PURPOSE This study reports the surgical results in those patients who underwent carotid endarterectomy in the North American Symptomatic Carotid Endarterectomy Trial ( NASCET ) . METHODS The rates of perioperative stroke and death at 30 days and the final assessment of stroke severity at 90 days were calculated . Regression modeling was used to identify variables that increased or decreased perioperative risk . Non outcome surgical complications were summarized . The durability of carotid endarterectomy was examined . RESULTS In 1415 patients there were 92 perioperative outcome events , for an overall rate of 6.5 % . At 30 days the results were as follows : death , 1.1 % ; disabling stroke , 1.8 % ; and nondisabling stroke , 3.7 % . At 90 days , because of improvement in the neurological status of patients judged to have been disabled at 30 days , the results were as follows : death , 1.1 % ; disabling stroke , 0.9 % ; and nondisabling stroke , 4.5 % . Thirty events occurred intraoperatively ; 62 were delayed . Most strokes result ed from thromboembolism . Five baseline variables were predictive of increased surgical risk : hemispheric versus retinal transient ischemic attack as the qualifying event , left-sided procedure , contralateral carotid occlusion , ipsilateral ischemic lesion on CT scan , and irregular or ulcerated ipsilateral plaque . History of coronary artery disease with prior cardiac procedure was associated with reduced risk . The risk of perioperative wound complications was 9.3 % , and that of cranial nerve injuries was 8.6 % ; most were of mild severity . At 8 years , the risk of disabling ipsilateral stroke was 5.7 % , and that of any ipsilateral stroke was 17.1 % . CONCLUSIONS The overall rate of perioperative stroke and death was 6.5 % , but the rate of permanently disabling stroke and death was only 2.0 % . Other surgical complications were rarely clinical ly important . Carotid endarterectomy is a durable procedure The Feasibility And Safety Trial for its embolic protection device during transluminal intervention in coronary vessels : a European Registry ( FASTER ) was design ed to demonstrate that ( 1 ) the Proxis embolic protection system can control antero grade flow and reverse blood flow in native coronary arteries and saphenous vein grafts ; and ( 2 ) this system can capture embolic debris . Percutaneous coronary intervention on stenotic coronary lesions revolutionized treatment of coronary disease , but is associated with the risk of major adverse cardiac events . This prospect i ve , nonr and omized , multicenter clinical feasibility and safety study enrolled 40 patients with 51 lesions at 4 centers who underwent treatment of stenotic lesions with proximal emboli protection ( Proxis system ) . Proxis was successfully used 95 % of the time , and embolic debris was qualitatively identified in all cases . Major adverse cardiac events occurred in 2 patients ( 5.0 % ) : 1 late in-stent thrombosis result ing in death and 1 non-Q-wave infa rct ion when a lesion was crossed before deployment of the Proxis system . Mean vessel occlusion time was 4.3 + /- 2.4 minutes . Native flow reversal was sufficient in 31 patients , with a mean aspirate volume of 11.8 + /- 6.5 ml . When the infusion catheter was used to augment reflow , mean occlusion time was 4.6 minutes . In conclusion , this trial is the first to demonstrate that retro grade blood flow can be achieved during proximal occlusion and that the Proxis system can be used safely during intervention of saphenous vein grafts and native coronary arterial lesions to capture embolic material BACKGROUND The efficacy of carotid endarterectomy for selected patients has been evaluated with r and omized controlled clinical trials . The generalizability of these studies to average surgical practice remains an important public health concern . OBJECTIVE The objective of the study was to determine the predictors of outcome after carotid endarterectomy on a regional basis . PATIENTS AND METHODS The study was design ed as a retrospective cohort study and included all consecutive patients presented for carotid endarterectomy at the 8 University of Toronto-affiliated hospitals in the period from January 1 , 1994 , to December 31 , 1996 . The main outcome measure was 30-day postoperative stroke or death rate . RESULTS During the study interval , 1280 primary carotid endarterectomies were performed . The overall combined stroke and death rate was 6.3 % for all patients who underwent endarterectomy ( 4.0 % for patients who were asymptomatic ) . The significant predictors of poor outcome were the following : presenting symptoms ( odds ratio , 1.74 ; 95 % confidence interval [ CI ] , 0.96 , 3.12 ) , low surgeon volume ( < 6 cases per year ; odds ratio , 3.98 ; 95 % CI , 1.65 , 9.58 ) , and left-sided surgery ( odds ratio , 1.72 ; 95 % CI , 1.07 , 2.76 ) . CONCLUSION These data suggest that adoption of the recommendations of the symptomatic carotid endarterectomy trials is appropriate . However , endarterectomy for asymptomatic lesions remains of uncertain benefit on a regional basis and must be individualized to the experience of the specific surgeon . The surgeon volume/ outcome relationship that is identified in this study suggests a need for a minimum volume threshold for this procedure BACKGROUND Without strong evidence of benefit , the use of carotid endarterectomy for prophylaxis against stroke rose dramatically until the mid-1980s , then declined . Our investigation sought to determine whether carotid endarterectomy reduces the risk of stroke among patients with a recent adverse cerebrovascular event and ipsilateral carotid stenosis . METHODS We conducted a r and omized trial at 50 clinical centers throughout the United States and Canada , in patients in two predetermined strata based on the severity of carotid stenosis--30 to 69 percent and 70 to 99 percent . We report here the results in the 659 patients in the latter stratum , who had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic carotid artery . All patients received optimal medical care , including antiplatelet therapy . Those assigned to surgical treatment underwent carotid endarterectomy performed by neurosurgeons or vascular surgeons . All patients were examined by neurologists 1 , 3 , 6 , 9 , and 12 months after entry and then every 4 months . End points were assessed by blinded , independent case review . No patient was lost to follow-up . RESULTS Life-table estimates of the cumulative risk of any ipsilateral stroke at two years were 26 percent in the 331 medical patients and 9 percent in the 328 surgical patients --an absolute risk reduction ( + /- SE ) 17 + /- 3.5 percent ( P less than 0.001 ) . For a major or fatal ipsilateral stroke , the corresponding estimates were 13.1 percent and 2.5 percent -- an absolute risk reduction of 10.6 + /- 2.6 percent ( P less than 0.001 ) . Carotid endarterectomy was still found to be beneficial when all strokes and deaths were included in the analysis ( P less than 0.001 ) . CONCLUSIONS Carotid endarterectomy is highly beneficial to patients with recent hemispheric and retinal transient ischemic attacks or nondisabling strokes and ipsilateral high- grade stenosis ( 70 to 99 percent ) of the internal carotid artery BACKGROUND Our objective was to assess the risks and benefits of carotid endarterectomy , primarily in terms of stroke prevention , in patients with recently symptomatic carotid stenosis . METHODS This multicentre , r and omised controlled trial enrolled 3024 patients . We enrolled men and women of any age , with some degree of carotid stenosis , who within the previous 6 months had had at least one transient or mild symptomatic ischaemic vascular event in the distribution of one or both carotid arteries . Between 1981 and 1994 , we allocated 1811 ( 60 % ) patients to surgery and 1213 ( 40 % ) to control ( surgery to be avoided for as long as possible ) . Follow-up was until the end of 1995 ( mean 6.1 years ) , and the main analyses were by intention to treat . FINDINGS The overall outcome ( major stroke or death ) occurred in 669 ( 37.0 % ) surgery-group patients and 442 ( 36.5 % ) control-group patients . The risk of major stroke or death complicating surgery ( 7.0 % ) did not vary substantially with severity of stenosis . On the other h and , the risk of major ischaemic stroke ipsilateral to the unoperated symptomatic carotid artery increased with severity of stenosis , particularly above about 70 - 80 % of the original luminal diameter , but only for 2 - 3 years after r and omisation . On average , the immediate risk of surgery was worth trading off against the long-term risk of stroke without surgery when the stenosis was greater than about 80 % diameter ; the Kaplan-Meier estimate of the frequency of a major stroke or death at 3 years was 26.5 % for the control group and 14.9 % for the surgery group , an absolute benefit from surgery of 11.6 % . However , consideration of variations in risk with age and sex modified this simple rule based on stenosis severity . We present a graphical procedure that should improve the selection of patients for surgery . INTERPRETATION Carotid endarterectomy is indicated for most patients with a recent non-disabling carotid-territory ischaemic event when the symptomatic stenosis is greater than about 80 % . Age and sex should also be taken into account in decisions on whether to operate OBJECTIVES Neurologic complications during carotid artery stenting ( CAS ) are most clearly associated with embolization of visible debris . Distal filter devices may provide cerebr Output:	Left-sided CE is consistently associated with higher postoperative adverse event rates .
MS21987	*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 perform a r and omized trial comparing 70 and 80 Gy radiotherapy for prostate cancer . PATIENTS AND METHODS A total of 306 patients with localized prostate cancer were r and omized . No and rogen deprivation was allowed . The primary endpoint was biochemical relapse according to the modified 1997-American Society for Therapeutic Radiology and Oncology and Phoenix definitions . Toxicity was grade d using the Radiation Therapy Oncology Group 1991 criteria and the late effects on normal tissues-subjective , objective , management , analytic scales ( LENT-SOMA ) scales . The patients ' quality of life was scored using the European Organization for Research and Treatment of Cancer Quality of Life Question naire 30-item cancer-specific and 25-item prostate-specific modules . RESULTS The median follow-up was 61 months . According to the 1997-American Society for Therapeutic Radiology and Oncology definition , the 5-year biochemical relapse rate was 39 % and 28 % in the 70- and 80-Gy arms , respectively ( p = .036 ) . Using the Phoenix definition , the 5-year biochemical relapse rate was 32 % and 23.5 % , respectively ( p = .09 ) . The subgroup analysis showed a better biochemical outcome for the higher dose group with an initial prostate-specific antigen level > 15 ng/mL. At the last follow-up date , 26 patients had died , 10 of their disease and none of toxicity , with no differences between the two arms . According to the Radiation Therapy Oncology Group scale , the Grade 2 or greater rectal toxicity rate was 14 % and 19.5 % for the 70- and 80-Gy arms ( p = .22 ) , respectively . The Grade 2 or greater urinary toxicity was 10 % at 70 Gy and 17.5 % at 80 Gy ( p = .046 ) . Similar results were observed using the LENT-SOMA scale . Bladder toxicity was more frequent at 80 Gy than at 70 Gy ( p = .039 ) . The quality -of-life question naire results before and 5 years after treatment were available for 103 patients with no differences found between the 70- and 80-Gy arms . CONCLUSION High-dose radiotherapy provided a better 5-year biochemical outcome with slightly greater toxicity Abstract The urinary bladder shows considerable individual variation in shape and position during a course of radiotherapy ( RT ) . In this study we have developed and compared three different adaptive RT ( ART ) strategies for bladder cancer involving daily cone beam CT ( CBCT ) imaging and plan selection . Material and methods . Ten patients treated for bladder cancer had daily CBCTs acquired that were registered online using bony anatomy registration . Seven patients received intensity modulated RT ( IMRT ) with a simultaneous integrated boost ( SIB ) technique to the bladder and pelvic lymph nodes . Three patients received treatment to the bladder only . Retrospectively , we compared three ART strategies that were all based on daily selection of the most suitable plan from a library consisting of three IMRT-plans corresponding to a small , medium and large target volume . ART method A utilised population -based margins while methods B and C used the bladder as seen on CBCT-scans from the first week of treatment ; method B without delineation of the bladder on CBCT and method C with delineation of the bladder . Total dose distributions were calculated using the planning CT . For each patient , we calculated ratios of the dose volume histograms ( DVHs ) for the three ART strategies relative to non-adaptive therapy . Results . The inter-patient variation was large for all three ART strategies . The mean ratios of the volumes receiving 57 Gy or more ( corresponding to 95 % of prescribed dose ) for methods A , B and C were 0.66 ( SD : 0.11 ) , 0.67 ( SD : 0.13 ) and 0.67 ( SD : 0.16 ) respectively when compared to the non-adaptive plan . Conclusion . When using any of the ART strategies , it is possible to reduce significantly the volumes receiving high doses compared to the use of a st and ard non-adaptive plan . The differences in dose volume parameters between the three methods were small compared with the differences from the st and ard plan Background To analyse the overall clinical outcome and benefits by applying protocol based image guided adaptive brachytherapy combined with 3D conformal external beam radiotherapy ( EBRT ) ± chemotherapy ( ChT ) . Methods Treatment schedule was EBRT with 45–50.4 Gy ± concomitant cisplatin chemotherapy plus 4 × 7 Gy High Dose Rate ( HDR ) brachytherapy . Patients were treated in the “ protocol period ” ( 2001–2008 ) with the prospect i ve application of the High Risk CTV concept ( D90 ) and dose volume constraints for organs at risk including biological modelling . Dose volume adaptation was performed with the aim of dose escalation in large tumours ( prescribed D90 > 85 Gy ) , often with inserting additional interstitial needles . Dose volume constraints ( D2cc ) were 70–75 Gy for rectum and sigmoid and 90 Gy for bladder . Late morbidity was prospect ively scored , using LENT/SOMA Score . Disease outcome and treatment related late morbidity were evaluated and compared using actuarial analysis . Findings One hundred and fifty-six consecutive patients ( median age 58 years ) with cervix cancer FIGO stages IB – IVA were treated with definitive radiotherapy in curative intent . Histology was squamous cell cancer in 134 patients ( 86 % ) , tumour size was > 5 cm in 103 patients ( 66 % ) , lymph node involvement in 75 patients ( 48 % ) . Median follow-up was 42 months for all patients . Interstitial techniques were used in addition to intracavitary brachytherapy in 69/156 ( 44 % ) patients . Total prescribed mean dose ( D90 ) was 93 ± 13 Gy , D2cc 86 ± 17 Gy for bladder , 65 ± 9 Gy for rectum and 64 ± 9 Gy for sigmoid . Complete remission was achieved in 151/156 patients ( 97 % ) . Overall local control at 3 years was 95 % ; 98 % for tumours 2–5 cm , and 92 % for tumours > 5 cm ( p = 0.04 ) , 100 % for IB , 96 % for IIB , 86 % for IIIB . Cancer specific survival at 3 years was overall 74 % , 83 % for tumours 2–5 cm , 70 % for tumours > 5 cm , 83 % for IB , 84 % for IIB , 52 % for IIIB . Overall survival at 3 years was in total 68 % , 72 % for tumours 2–5 cm , 65 % for tumours > 5 cm , 74 % for IB , 78 % for IIB , 45 % for IIIB . In regard to late morbidity in total 188 grade 1 + 2 and 11 grade 3 + 4 late events were observed in 143 patients . G1 + 2/G3 + 4 events for bladder were n = 32/3 , for rectum n = 14/5 , for bowel ( including sigmoid ) n = 3/0 , for vagina n = 128/2 , respectively . Interpretation 3D conformal radiotherapy ± chemotherapy plus image ( MRI ) guided adaptive intracavitary brachytherapy including needle insertion in advanced disease results in local control rates of 95–100 % at 3 years in limited/favourable ( IB/IIB ) and 85–90 % in large/poor response ( IIB/III/IV ) cervix cancer patients associated with a moderate rate of treatment related morbidity . Compared to the historical Vienna series there is relative reduction in pelvic recurrence by 65–70 % and reduction in major morbidity . The local control improvement seems to have impact on CSS and OS . Prospect i ve clinical multi-centre studies are m and atory to evaluate these challenging mono-institutional findings Abstract Background . The first Nordic protocol for three-dimensional ( 3D ) planned radiotherapy in locally advanced cervical cancer was the prospect i ve NOCECA study ( 1994–2000 ) . NOCECA consisted of computed tomography (CT)-based 3D conformal external beam radiotherapy ( EBRT ) with a simultaneous integrated boost ( SIB ) to the primary tumour combined with brachytherapy ( BT ) based on x-ray imaging . In NOCECA the planning aim was to achieve 80 Gy at point A from EBRT and BT combined . However , the balance of dose between EBRT and BT was determined by tumour size at diagnosis with more EBRT dose given to point A and less by BT in more advanced stages . In 2005 image-guided adaptive brachytherapy ( IGABT ) based on magnetic resonance imaging ( MRI ) and optimisation of the BT dose distribution to the remaining tumour and cervix at time of BT ( HR CTV ) was introduced in Aarhus . EBRT remained like in NOCECA until 2008 when the SIB to the primary tumour was ab and oned and IMRT was introduced as routine technique . In this study , we report outcome of our first five-year experience with IGABT using our NOCECA cohort as reference . Material and methods . The NOCECA cohort comprising 99 patients was compared with 140 consecutive patients treated by IGABT . Patients with para-aortic nodes were excluded in NOCECA but were present in 9 % of the patients treated with IGABT . No patient in NOCECA received chemotherapy whereas concomitant cisplatin was given to 79 % of the IGABT patients . Results . With IGABT actuarial local control was 91 % at three years . When comparing NOCECA with IGABT overall survival was significantly improved from 63 % to 79 % ( p = 0.005 ) . In parallel , both moderate and severe late morbidity were reduced by about 50 % ( p = 0.02 ) . Conclusion . Introduction of IGABT reduced morbidity and generated a very high rate of local control , which likely has improved survival by at least as much as concomitant chemotherapy PURPOSE Report of clinical cancer control outcomes on Radiation Therapy Oncology Group ( RTOG ) 9406 , a three-dimensional conformal radiation therapy ( 3D-CRT ) dose escalation trial for localized adenocarcinoma of the prostate . METHODS AND MATERIAL S RTOG 9406 is a Phase I/II multi-institutional dose escalation study of 3D-CRT for men with localized prostate cancer . Patients were registered on five sequential dose levels : 68.4 Gy , 73.8 Gy , 79.2 Gy , 74 Gy , and 78 Gy with 1.8 Gy/day ( levels I-III ) or 2.0 Gy/day ( levels IV and V ) . Neoadjuvant hormone therapy ( NHT ) from 2 to 6 months was allowed . Protocol -specific , American Society for Therapeutic Radiation Oncology ( ASTRO ) , and Phoenix biochemical failure definitions are reported . RESULTS Thirty-four institutions enrolled 1,084 patients and 1,051 patients are analyzable . Median follow-up for levels I , II , III , IV , and V was 11.7 , 10.4 , 11.8 , 10.4 , and 9.2 years , respectively . Thirty-six percent of patients received NHT . The 5-year overall survival was 90 % , 87 % , 88 % , 89 % , and 88 % for dose levels I-V , respectively . The 5-year clinical disease-free survival ( excluding protocol prostate-specific antigen definition ) for levels I-V is 84 % , 78 % , 81 % , 82 % , and 82 % , respectively . By ASTRO definition , the 5-year disease-free survivals were 57 % , 59 % , 52 % , 64 % and 75 % ( low risk ) ; 46 % , 52 % , 54 % , 56 % , and 63 % ( intermediate risk ) ; and 50 % , 34 % , 46 % , 34 % , and 61 % ( high risk ) for levels I-V , respectively . By the Phoenix definition , the 5-year disease-free survivals were 68 % , 73 % , 67 % , 84 % , and 80 % ( low risk ) ; 70 % , 62 % , 70 % , 74 % , and 69 % ( intermediate risk ) ; and 42 % , 62 % , 68 % , 54 % , and 67 % ( high risk ) for levels I-V , respectively . CONCLUSION Dose-escalated 3D-CRT yields favorable outcomes for localized prostate cancer . This multi-institutional experience allows comparison to other experiences with modern radiation therapy This study compares three online image guidance techniques ( IGRT ) for prostate IMRT treatment : bony-anatomy matching , soft-tissue matching , and online replanning . Six prostate IMRT patients were studied . Five daily CBCT scans from the first week were acquired for each patient to provide representative " snapshots " of anatomical variations during the course of treatment . Initial IMRT plans were design ed for each patient with seven coplanar 15 MV beams on a Output:	Advantageous dosimetric and outcome patterns using ART was documented by the studies of this review . Despite this , clinical implementations were scarce due to challenges in target/organ re-contouring and suboptimal patient selection in the ART workflows
MS21988	*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 was a prospect i ve double blind comparative study on 40 patients . It compared the effects of the leukotriene receptor antagonist montelukast and beclomethasone nasal spray on the post-operative course of patients with sinonasal polyps . All patients underwent endoscopic sphenoethmoidectomy and were r and omized post-operatively into two groups . Group I : 20 patients ( 9 females and 11 males ) age 17 to 67 ( 32.4 ± 9.5 years ) , receiving 10 mg montelukast orally daily and Group II : 20 patients ( 6 females and 14 males ) age 17 years to 57 years ( 33.5 ± 11.9 years ) , receiving 400 ug beclomethasone local sprays daily . All patients were followed up for 1 year and a symptom score was recorded throughout this period . There was a significant reduction in symptom scores in both groups throughout the study period . In the montelukast group improvement was more marked in itching , post-nasal discharge and headache . The control of sneezing and rhinorrhea was comparable in both groups with a marginal advantage of montelukast . Steroids had a more marked effect on smell disturbances and obstruction . There was no difference in the recurrence rate or in the need for rescue medications between both groups . Both drugs seem to have a complementary action and further studies are needed to determine which patients should receive which treatment BACKGROUND Leukotrienes , especially LTC4 , are important inflammatory mediators in allergic and nonallergic inflammation of the entire airways . Of particular interest are numerous theories regarding the pathogenesis of aspirin intolerance with subsequent hyperproduction of leukotrienes and inhibition of cyclooxygenase . OBJECTIVE To examine the influence of the cysteinyl-leukotriene receptor antagonist montelukast on clinical symptoms and inflammatory markers in nasal lavage fluid in patients with bronchial asthma and nasal polyps , and determine its dependency on aspirin sensitization . METHODS Twenty-four patients ( 7 women , 17 men ; median age , 55.5 years ) with nasal polyps and controlled asthma ( n=12 with aspirin intolerance ) were treated with 10 mg montelukast once daily for 6 weeks in a blinded , placebo-controlled fashion . The placebo phase was r and omly assigned 4 weeks before ( n=12 ) or after treatment ( n=12 ) . Symptom score , rhinoendoscopy , rhinomanometry , smears for eosinophils , and nasal lavages for the determination of different mediators were performed . RESULTS Compared to placebo , there were significant improvements in the nasal symptom score and airflow limitation as well as a reduction in the inflammatory mediators in nasal lavage fluid after treatment . Furthermore , reduced eosinophils in nasal smears and peripheral blood were observed 2 and 6 weeks after treatment . CONCLUSION Leukotriene 1 receptor blockade led to a significant decrease in eosinophil inflammation accompanied by a reduction in other mediators such as neurokinin A and substance P in the nasal lavage fluid of patients with nasal polyps and asthma , with or without aspirin intolerance Objective To examine the potential of montelukast , a leukotriene receptor antagonist , as an adjunct to oral and inhaled steroid in subjects with chronic nasal polyps . Study Design Prospect i ve , r and omized controlled trial . Subjects and Methods Thirty-eight consecutive adult patients with bilateral nasal polyps were r and omized into two groups . Eighteen subjects were treated with oral prednisolone for 14 days and budenoside nasal spray for 8 weeks . Twenty subjects received similar treatment with additional oral montelukast for 8 weeks . Subjects completed a modified nasal ICSD symptom score at 8 and 12 weeks after beginning treatment and the SF-36 quality of life question naire at 12 weeks . Results Symptom scores improved in both groups after treatment . Subjects treated with montelukast reported significantly less headache ( P = 0.013 ) , facial pain ( P = 0.048 ) and sneezing ( P = 0.03 ) than controls . Four weeks after completing treatment , no significant differences were recorded . Conclusion Montelukast therapy may have clinical benefit as an adjunct to oral and inhaled steroid in chronic nasal polyposis , but effects are not maintained after cessation of treatment The leukotrienes are known to be important mediators of bronchial asthma . The ability of montelukast , a potent and selective CysLT1 leukotriene receptor antagonist , to cause a dose-related improvement in chronic asthma was investigated in a placebo-controlled , multicentre , parallel-group study . After a two week placebo run-in period , chronic asthmatic patients with a forced expiratory volume in one second ( FEV1 ) 40 - 80 % predicted with > or = 15 % increase ( absolute value ) after beta2-agonist were r and omly assigned to one of four treatment groups ( placebo or montelukast 2 , 10 , or 50 mg once daily in the evening ) for a three week , double-blind treatment period . For patient-reported end-points ( daytime symptom score , use of as needed inhaled beta2 agonist , asthma-specific quality of life ) and frequency of asthma exacerbations , montelukast 10 and 50 mg caused similar responses , superior to 2 mg and significantly ( p<0.05 ; linear trend test ) different from placebo . All three doses caused improvements in FEV1 and morning and evening peak expiratory flow rate ( PEFR ) that were significantly ( p<0.05 ) different from placebo . Differences ( least square mean ) between the pooled 10 and 50 mg montelukast treatment groups and placebo were : 7.1 % change from baseline in FEV1 , 19.23 L x min(-1 ) in morning PEFR , -0.29 in daytime asthma symptom score ( absolute value ) , and -0.82 in beta2-agonist use ( puff x day(-1 ) ) . The incidence of adverse experiences was neither dose-related nor different between montelukast and placebo treatments . We conclude that montelukast causes a dose-related improvement in patient-reported asthma end-points over the range 2 - 50 mg . Montelukast causes benefit to chronic asthmatic patients by improving asthma control end-points Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE : To investigate the hypothesis that eosinophil major basic protein is released in high concentrations in the nasal mucus of patients with polypoid chronic rhinosinusitis . STUDY DESIGN : Single center , open , prospect i ve trial . SETTING : Medical University of Graz , Austria . SUBJECTS AND METHODS : Patients with polypoid chronic rhinosinusitis ( n = 23 ) were compared to three different control groups : patients with chronic rhinosinusitis-like symptoms but without general mucosal thickening , patients who underwent functional endoscopic sinus surgery for reasons other than chronic rhinosinusitis , and patients without sinus disease ( total n = 21 ) . Mucus was harvested from each patient using a st and ardized technique and analyzed for eosinophil major basic protein with an enzyme-linked immunosorbent assay . RESULTS : In the patient group with polypoid chronic rhinosinusitis , 20 of 23 ( 87 % ) were positive for eosinophil major basic protein . In contrast , only one control patient was positive , whereas the remainder had no detectable amount of eosinophil major basic protein in the mucus ( P = 0.001 vs chronic rhinosinusitis ) . CONCLUSION : Toxic eosinophil major basic protein levels are elevated in polypoid chronic rhinosinusitis patients compared to control groups that have similar clinical presentations but upon closer examination turn out not to have chronic rhinosinusitis . In the future , the detection of eosinophil major basic protein in nasal mucus may become a sensitive and specific marker for chronic rhinosinusitis and a helpful diagnostic tool . © 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation . All rights reserved Eosinophils are the principal effector cells involved in the pathogenesis of allergic inflammation . We conducted a study to investigate the validity of the nasal smear examination for detecting eosinophilia in patients with allergic rhinitis . Our study group was made up of 50 patients with allergic rhinitis and 50 age- and sex-matched controls without allergic rhinitis . Smears were obtained from nasal secretions in both groups and then fixed , stained , and studied under light microscopy . Statistical analysis revealed that the odds ratio for eosinophilia positivity in nasal smears in the rhinitis group was 25.61 with a 95 % confidence interval of 8 to 78 . The sensitivity , specificity , positive predictive value , and negative predictive value of this test were 74 , 90 , 88 , and 77 % , respectively . We conclude that the nasal eosinophilia test is highly specific and moderately sensitive in diagnosing allergic rhinitis , and that it therefore can be used as an easy , noninvasive , and inexpensive procedure for screening patients and for conducting epidemiologic studies of this disorder Background We assessed the course of treatment in patients with persistent allergic rhinitis ( AR ) treated with montelukast , levocetirizine , or desloratadine alone or combinations of antihistamine and montelukast . Methods A 32-week r and omized , double-blind , placebo-controlled , crossover , double-armed study in 40 adult patients with history of persistent AR , clinical allergy to house-dust mites , and a total nasal symptom score of at least 5 ( congestion of at least 2 ) has been performed . Patients with asthma , chronic obstructive pulmonary disease , nonallergic rhinitis with clinical allergy associated with seasonal allergens , and other serious diseases were excluded . There were four 6-week treatment periods separated by 2-week washout periods . Twenty patients received either montelukast or antihistamine , a combination of montelukast and antihistamine , or placebo . The sequence of treatment was r and omly assigned . Nasal symptoms were assessed using a 4-point scale at baseline , daily during the 1st week and on days 14 , 21 , 28 , 35 , and 42 of treatment . Results Montelukast alone , levocetirizine alone , desloratadine alone , and the montelukast/antihistamine combinations significantly improved nasal symptoms during the first 24 hours . Improvement gradually increased during the 6 weeks of treatment , especially in patients receiving montelukast alone or in combination therapy with the antihistamine in both arms . Improvement at 42 days of treatment was significantly greater than that achieved on the 1st day of therapy in patients treated with the combination of montelukast and levocetirizine . Conclusion Montelukast alone or in combination with antihistamines gave a gradual increase in nasal symptom improvement within 6 weeks of treatment in patients with persistent AR OBJECTIVES In this study we investigated the effect of adding montelukast to the treatment of nasal polyposis patients with bronchial asthma on quality of life . PATIENTS AND METHODS Thirty consecutive subjects with nasal polyposis accompanying bronchial asthma treated in our clinic were prospect ively evaluated . Subjects with aspirin hypersensitivity and seasonal allergic rhinitis were excluded . Patients were evaluated using the Turkish version of rhinosinusitis disability index ( RSDI ) and visual analog scores before the montelukast therapy , one and three months after the therapy started . It must be noted that in addition to being treated with anti-leukotriene therapy , all of these subjects continued to receive routine nasal steroid treatment . In all subjects paranasal sinus tomography scans were obtained during the study . Lund-Mackay staging system , which is a radiological scoring system , was used in the staging of the disease severity . RESULTS Rhinosinusitis disability index scores improved during the study period . Functional , emotional and physical sub-scales of RSDI were compared separately . But 1st and 3rd month scores are not statistically significant when compared with scores previous to montelukast therapy ( p>0.05 ) . Visual analog scale also showed a statistically significant decrease during the study period ( p<0.01 ) . Lund-Mackay staging did not show a statistically significant difference during the study period ( p>0.05 ) . CONCLUSION This study showed that montelukast therapy might have a clinical benefit as an adjunct to nasal steroids in subjects with nasal polyposis accompanying bronchial asthma We have studied the immunohistology of the nasal mucosa in allergen-induced rhinitis . Sixteen grass pollen-sensitive patients were challenged twice by r and omly allocated allergen or control solutions applied on filter paper disks to the inferior turbinate . All had immediate nasal responses , but late-phase responses were equivocal and only evident as nostril blockage . When cell counts in the nasal submucosa were compared with control values 24 h after allergen , there were no changes in CD45 + ( total leukocytes ) , CD3 + , or CD8 + cells . Significant increases were found in the numbers of CD4 + T-helper cells ( p less than 0.05 ) and CD25 + [ interleukin- Output:	Improvement was described by all studies in symptoms , clinical outcomes , and /or immune parameters after LTA treatment , with greater improvements in a subset of symptoms beyond that observed with INCSs . Concomitant asthma , aspirin-exacerbated respiratory disease , and atopy did not significantly or consistently affect these results . Conclusion LTAs are an effective tool for treating CRSwNP , with limited benefit as an adjunctive therapy .
MS21989	*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 effects of a carbohydrate-restricted diet on weight loss and risk factors for atherosclerosis have been incompletely assessed . METHODS We r and omly assigned 132 severely obese subjects ( including 77 blacks and 23 women ) with a mean body-mass index of 43 and a high prevalence of diabetes ( 39 percent ) or the metabolic syndrome ( 43 percent ) to a carbohydrate-restricted ( low-carbohydrate ) diet or a calorie- and fat-restricted ( low-fat ) diet . RESULTS Seventy-nine subjects completed the six-month study . An analysis including all subjects , with the last observation carried forward for those who dropped out , showed that subjects on the low-carbohydrate diet lost more weight than those on the low-fat diet ( mean [ + /-SD ] , -5.8+/-8.6 kg vs. -1.9+/-4.2 kg ; P=0.002 ) and had greater decreases in triglyceride levels ( mean , -20+/-43 percent vs. -4+/-31 percent ; P=0.001 ) , irrespective of the use or nonuse of hypoglycemic or lipid-lowering medications . Insulin sensitivity , measured only in subjects without diabetes , also improved more among subjects on the low-carbohydrate diet ( 6+/-9 percent vs. -3+/-8 percent , P=0.01 ) . The amount of weight lost ( P<0.001 ) and assignment to the low-carbohydrate diet ( P=0.01 ) were independent predictors of improvement in triglyceride levels and insulin sensitivity . CONCLUSIONS Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorie- and fat-restricted diet , with a relative improvement in insulin sensitivity and triglyceride levels , even after adjustment for the amount of weight lost . This finding should be interpreted with caution , given the small magnitude of overall and between-group differences in weight loss in these markedly obese subjects and the short duration of the study . Future studies evaluating long-term cardiovascular outcomes are needed before a carbohydrate-restricted diet can be endorsed This study examined the effects of dietary weight loss and exercise on the health-related quality of life ( HRQL ) of overweight and obese , older adults with knee osteoarthritis . A total of 316 older men and women with documented evidence of knee osteoarthritis were r and omly assigned to 1 of 4 18-month interventions : dietary weight loss , exercise , dietary weight loss and exercise , or healthy lifestyle control . Measures included the SF-36 Health Survey and satisfaction with body function and appearance . Results revealed that the combined diet and exercise intervention had the most consistent , positive effect on HRQL compared with the control group ; however , findings were restricted to measures of physical health or psychological outcomes that are related to the physical self Sedentary adults ( N = 379 ) were r and omly assigned in a 2 x 2 design to walk 30 min per day at a frequency of either 3 - 4 or 5 - 7 days per week , at an intensity of either 45%-55 % or 65%-75 % of maximum heart rate reserve . Analyses of exercise accumulated over 6 months showed greater amounts completed in the higher frequency ( p = .0001 ) and moderate intensity ( p = .021 ) conditions . Analyses of percentage of prescribed exercise completed showed greater adherence in the moderate intensity(p = .02 ) condition . Prescribing a higher frequency increased the accumulation of exercise without a decline in adherence , whereas prescribing a higher intensity decreased adherence and result ed in the completion of less exercise CONTEXT Rapid increases in access to the Internet have made it a viable mode for public health intervention . No controlled studies have evaluated this re source for weight loss . OBJECTIVE To determine whether a structured Internet behavioral weight loss program produces greater initial weight loss and changes in waist circumference than a weight loss education Web site . DESIGN R and omized , controlled trial conducted from April to December 1999 . SETTING AND PARTICIPANTS Ninety-one healthy , overweight adult hospital employees aged 18 to 60 years with a body mass index of 25 to 36 kg/m(2 ) . Analyses were performed for the 65 who had complete follow-up data . INTERVENTIONS Participants were r and omly assigned to a 6-month weight loss program of either Internet education ( education ; n = 32 with complete data ) or Internet behavior therapy ( behavior therapy ; n = 33 with complete data ) . All participants were given 1 face-to-face group weight loss session and access to a Web site with organized links to Internet weight loss re sources . Participants in the behavior therapy group received additional behavioral procedures , including a sequence of 24 weekly behavioral lessons via e-mail , weekly online su bmi ssion of self-monitoring diaries with individualized therapist feedback via e-mail , and an online bulletin board . MAIN OUTCOME MEASURES Body weight and waist circumference , measured at 0 , 3 , and 6 months , compared the 2 intervention groups . RESULTS Repeated- measures analyses showed that the behavior therapy group lost more weight than the education group ( P = .005 ) . The behavior therapy group lost a mean ( SD ) of 4.0 ( 2.8 ) kg by 3 months and 4.1 ( 4.5 ) kg by 6 months . Weight loss in the education group was 1.7 ( 2.7 ) kg at 3 months and 1.6 ( 3.3 ) kg by 6 months . More participants in the behavior therapy than education group achieved the 5 % weight loss goal ( 45 % vs 22 % ; P = .05 ) by 6 months . Changes in waist circumference were also greater in the behavior therapy group than in the education group at both 3 months ( P = .001 ) and 6 months ( P = .005 ) . CONCLUSIONS Participants who were given a structured behavioral treatment program with weekly contact and individualized feedback had better weight loss compared with those given links to educational Web sites . Thus , the Internet and e-mail appear to be viable methods for delivery of structured behavioral weight loss programs CONTEXT Although the use of electron beam tomography ( EBT ) as a motivational tool to change behavior is practice d , its efficacy has not been studied . OBJECTIVE To assess the effects of incorporating EBT as a motivational factor into a cardiovascular screening program in the context of either intensive case management ( ICM ) or usual care by assessing its impact over 1 year on a composite measure of projected risk . DESIGN R and omized controlled trial with a 2 x 2 factorial design and 1 year of follow-up . SETTING AND PARTICIPANTS A consecutive sample of 450 asymptomatic active-duty US Army personnel aged 39 to 45 years stationed within the Washington , DC , area and scheduled to undergo a periodic Army-m and ated physical examination were enrolled between January 1999 and March 2001 ( mean age , 42 years ; 79 % male ; 66 [ 15 % ] had coronary calcification ; mean [ SD ] predicted 10-year coronary risk , 5.85 % [ 3.85 % ] ) . INTERVENTIONS Patients were r and omly assigned to 1 of 4 intervention arms : EBT results provided in the setting of either ICM ( n = 111 ) or usual care ( n = 119 ) or EBT results withheld in the setting of either ICM ( n = 124 ) or usual care ( n = 96 ) . MAIN OUTCOME MEASURE The primary outcome measure was change in a composite measure of risk , the 10-year Framingham Risk Score ( FRS ) . RESULTS Comparing the groups who received EBT results with those who did not , the mean absolute risk change in 10-year FRS was + 0.30 vs + 0.36 ( P = .81 ) . Comparing the groups who received ICM with those who received usual care , the mean absolute risk change in 10-year FRS was -0.06 vs + 0.74 ( P = .003 ) . Improvement or stabilization of cardiovascular risk was noted in 157 patients ( 40.2 % ) . In multivariable analyses predicting change in FRS , after controlling for knowledge of coronary calcification , motivation for change , and multiple psychological variables , only the number of risk factors ( odds ratio , 1.42 ; 95 % confidence interval , 1.16 - 1.75 for each additional risk factor ) and receipt of ICM ( odds ratio , 1.62 ; 95 % confidence interval , 1.04 - 2.52 ) were associated with improved or stabilized projected risk . CONCLUSIONS Using coronary calcification screening to motivate patients to make evidence -based changes in risk factors was not associated with improvement in modifiable cardiovascular risk at 1 year . Case management was superior to usual care in the management of risk factors BACKGROUND We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas , which are precursors of most large-bowel cancers . METHODS We r and omly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before r and omization to one of two groups : an intervention group given intensive counseling and assigned to follow a diet that was low in fat ( 20 percent of total calories ) and high in fiber ( 18 g of dietary fiber per 1000 kcal ) and fruits and vegetables ( 3.5 servings per 1000 kcal ) , and a control group given a st and ard brochure on healthy eating and assigned to follow their usual diet . Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps ; they remained in the study for approximately four years , undergoing colonoscopy one and four years after r and omization . RESULTS A total of 1905 of the r and omized subjects ( 91.6 percent ) completed the study . Of the 958 subjects in the intervention group and the 947 in the control group who completed the study , 39.7 percent and 39.5 percent , respectively , had at least one recurrent adenoma ; the unadjusted risk ratio was 1.00 ( 95 percent confidence interval , 0.90 to 1.12 ) . Among subjects with recurrent adenomas , the mean ( + /-SE ) number of such lesions was 1.85+/-0.08 in the intervention group and 1.84+/-0.07 in the control group . The rate of recurrence of large adenomas ( with a maximal diameter of at least 1 cm ) and advanced adenomas ( defined as lesions that had a maximal diameter of at least 1 cm or at least 25 percent villous elements or evidence of high- grade dysplasia , including carcinoma ) did not differ significantly between the two groups . CONCLUSIONS Adopting a diet that is low in fat and high in fiber , fruits , and vegetables does not influence the risk of recurrence of colorectal adenomas Infertile women express higher levels of distress than fertile women , with distress peaking between the 2nd and 3rd year . The purpose of this study was to determine whether group psychological interventions could prevent this surge . One hundred eighty-four women who had been trying to conceive between 1 and 2 years were r and omized into either a cognitive-behavioral group , a support group , or a control group . All experimental participants attended a 10-session group program . Participants completed psychological question naires at intake and again at 6 and 12 months . Substantial attrition occurred , particularly in the control group . The cognitive-behavioral and support participants experienced significant psychological improvement at 6 and 12 months compared with the control participants , with the cognitive-behavioral participants experiencing the greatest positive change This study compared the effectiveness of 4 videotaped educational programs design ed to motivate HIV testing among low-income , ethnic minority women . Four hundred eighty women were assigned r and omly to watch one of 2 gain-framed or 2 loss-framed videos . Consistent with prospect theory , participants ' perceptions of the certainty of the outcome of an HIV test moderated the effects of framing on self-reported testing behavior 6 months after video exposure . Among participants who reported being certain of the test 's outcome , those who saw a gain-framed video reported a higher rate of testing than those who saw a loss-framed message . Among women who perceived the outcome of HIV testing as relatively uncertain , gain- and loss-framed videos led to similar rates of self-reported testing , with some advantage for the loss-framed message CONTEXT Depression and low perceived social support ( LPSS ) after myocardial infa rct ion ( MI ) are associated with higher morbidity and mortality , but little is known about whether this excess risk can be reduced through treatment . OBJECTIVE To determine whether mortality and recurrent infa rct ion are reduced by treatment of depression and LPSS with cognitive behavior therapy ( CBT ) , supplemented with a selective serotonin reuptake inhibitor ( SSRI ) antidepressant when indicated , in patients enrolled within 28 days after MI . DESIGN , SETTING , AND PATIENTS R and omized clinical trial conducted from October 1996 to April 2001 in 2481 MI patients ( 1084 women , 1397 men ) enrolled from 8 clinical centers . Major or minor depression was diagnosed by modified Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria and severity by the 17-item Hamilton Rating Scale for Depression ( H Output:	Findings revealed areas of weakness in analytic aspects of the behavioral health RCTs reported in both sets of journals . Weaknesses were more pronounced in behavioral journals .
MS21990	*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 Ischemic mitral regurgitation is associated with a substantial risk of death . Practice guidelines recommend surgery for patients with a severe form of this condition but acknowledge that the supporting evidence for repair or replacement is limited . METHODS We r and omly assigned 251 patients with severe ischemic mitral regurgitation to undergo either mitral-valve repair or chordal-sparing replacement in order to evaluate efficacy and safety . The primary end point was the left ventricular end-systolic volume index ( LVESVI ) at 12 months , as assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized below the lowest LVESVI rank . RESULTS At 12 months , the mean LVESVI among surviving patients was 54.6±25.0 ml per square meter of body-surface area in the repair group and 60.7±31.5 ml per square meter in the replacement group ( mean change from baseline , -6.6 and -6.8 ml per square meter , respectively ) . The rate of death was 14.3 % in the repair group and 17.6 % in the replacement group ( hazard ratio with repair , 0.79 ; 95 % confidence interval , 0.42 to 1.47 ; P=0.45 by the log-rank test ) . There was no significant between-group difference in LVESVI after adjustment for death ( z score , 1.33 ; P=0.18 ) . The rate of moderate or severe recurrence of mitral regurgitation at 12 months was higher in the repair group than in the replacement group ( 32.6 % vs. 2.3 % , P<0.001 ) . There were no significant between-group differences in the rate of a composite of major adverse cardiac or cerebrovascular events , in functional status , or in quality of life at 12 months . CONCLUSIONS We observed no significant difference in left ventricular reverse remodeling or survival at 12 months between patients who underwent mitral-valve repair and those who underwent mitral-valve replacement . Replacement provided a more durable correction of mitral regurgitation , but there was no significant between-group difference in clinical outcomes . ( Funded by the National Institutes of Health and the Canadian Institutes of Health ; Clinical Trials.gov number , NCT00807040 . ) Background — When compared to mitral valve replacement ( MVR ) , mitral valve repair ( MVRp ) is associated with better survival in patients with organic mitral regurgitation ( MR ) . However , there is an important controversy about the type of surgical treatment that should be used in patients with ischemic MR . The objective of this study was to compare the postoperative outcome of MVRp versus MVR in patients with ischemic MR . Methods and Results — Preoperative and operative data of 370 patients with ischemic MR who underwent mitral valve surgery were prospect ively collected and retrospectively analyzed . MVRp was performed in 50 % of patients ( n=186 ) and MVR in 50 % ( n=184 ) . Although operative mortality was significantly lower after MVRp compared to MVR ( 9.7 % versus 17.4 % ; P=0.03 ) , overall 6-year survival was not statistically different between procedures ( 73±4 % versus 67±4 % ; P=0.17 ) . After adjusting for other risk factors and propensity score , the type of procedure ( MVRp versus MVR ) did not come out as an independent predictor of either operative ( OR , 1.5 ; 95 % CI , 0.7–2.9 ; P=0.34 ) or overall mortality ( HR , 1.2 ; 95 % CI , 0.7–1.9 ; P=0.52 ) . Conclusion — As opposed to what has been reported in patients with organic MR , the results of this study suggest that MVRp is not superior to MVR with regard to operative and overall mortality in patients with ischemic MR . These findings provide support for the realization of a r and omized trial comparing these 2 treatment modalities BACKGROUND Mitral regurgitation ( MR ) may complicate acute myocardial infa rct ion ( MI ) . However , it is not known whether mild MR is an independent predictor of post-MI outcome . METHODS AND RESULTS The study cohort consisted of 727 Survival and Ventricular Enlargement Study patients who underwent cardiac catheterization , including left ventriculography , up to 16 days after MI . Left ventriculograms were analyzed for diastolic and systolic volumes , global left ventricular sphericity , extent of wall motion abnormality , and endocardial curvature . The presence of MR was related to the risk of developing a cardiovascular event during 3.5 years of follow-up . MR was present in 141 patients ( 19.4 % ) . Severe ( 3 + ) MR was present in only 2 patients . Patients with MR were more likely to have a persistently occluded infa rct artery ( MR versus no MR , 27.3 % versus 15.2 % ; P=.001 ) . Although the ejection fractions were similar , MR patients had larger end-systolic and end-diastolic volumes and more spherical ventricles than patients without MR . Sphericity change from diastole to systole was also significantly reduced in MR patients . Patients with MR were more likely to experience cardiovascular mortality ( 29 % versus 12 % ; P<.001 ) , severe heart failure ( 24 % versus 16 % ; P=.0153 ) , and the combined end point of cardiovascular mortality , severe heart failure , or recurrent myocardial infa rct ion ( 47 % versus 29 % ; P<.001 ) . The presence of MR was an independent predictor of cardiovascular mortality ( relative risk , 2.00 ; 95 % CI , 1.28 to 3.04 ) . CONCLUSIONS Mild MR is an independent predictor of post-MI mortality . As such , it adds important information for risk stratification of post-MI patients OBJECTIVES Mitral valve ( MV ) surgery for ischaemic mitral regurgitation ( IMR ) in patients with depressed left ventricular ejection fraction ( LVEF ) is associated with poor outcomes . The optimal surgical strategy for IMR in these patients remains controversial . The objective of this study was to compare the early mortality and mid-term survival of MV repair versus MV replacement in patients with IMR and depressed LVEF undergoing coronary artery bypass grafting ( CABG ) . METHODS A retrospective , observational , cohort study was undertaken of prospect ively collected data on 126 consecutive CABG patients with IMR and LVEF < 40 % undergoing either MV repair ( n = 98 , 78 % ) or MV replacement ( n = 28 , 22 % ) between July 2002 and February 2011 . RESULTS The overall mortality rate was 7.9 % ( n = 10 ) . MV replacement was associated with a 4-fold increase in the risk of death compared with MV repair [ 17.9 % , n = 5 vs 5.1 % , n = 5 ; odds ratio ( OR ) 4.04 , 95 % confidence interval ( CI ) 1.08 - 15.1 , P = 0.04 ] . However , after adjusting for preoperative risk factors , the type of surgical procedure was not an independent risk factor for early mortality ( OR 0.1 , 95 % CI 0.01 - 31 , P = 0.7 ) . Multivariable analysis showed that preoperative LVEF ( OR 0.8 , 95 % CI 0.6 - 0.9 , P = 0.018 ) , preoperative B-type natriuretic peptide ( BNP ) levels ( OR 1.01 , 95 % CI 1 - 1.02 , P = 0.025 ) , preoperative left ventricle end-systolic diameter ( OR 0.8 , 95 % CI 0.7 - 1.0 , P = 0.05 ) and preoperative left atrial diameter ( OR 1.3 , 95 % CI 1.0 - 1.6 , P = 0.015 ) were independent risk factors of early mortality . At the median follow-up of 45 months ( interquartile range 20 - 68 months ) , the mid-term survival rate was 74 % in the MV repair group and 70 % in the MV replacement group ( P = 0.08 ) . At follow-up , predictors of worse survival were BNP levels [ hazard ratio ( HR ) 1.0 , 95 % CI 1.0 - 1.01 , P = 0.047 ] , preoperative renal failure ( HR 4.6 , 95 % CI 1.1 - 20.3 , P = 0.039 ) and preoperative atrial fibrillation ( HR 3.3 , 95 % CI 1.1 - 10 , P = 0.032 ) . CONCLUSIONS MV repair in CABG patients with IMR and depressed LVEF is not superior to MV replacement with regard to operative early mortality and mid-term survival OBJECTIVE Mitral incompetence is a chronic sequela of myocardial infa rct ion . It is caused by apical displacement and tethering of the mitral valve leaflets after myocardial infa rct ion , result ing in incomplete coaptation . The consensus is for mitral valve surgery in the presence of significant ischemic mitral regurgitation ( IMR ) . Previously , the only option was mitral valve replacement ( MVR ) with a mechanical or tissue valve . The suboptimal results obtained prompted the development of several methods of mitral valve repair . Today , the most commonly used repair is undersized annuloplasty . METHODS We conducted a retrospective nonr and omized study of all patients who underwent operation for coronary artery disease and IMR between 2000 and 2006 . The surgeon chose the surgical method used for the mitral valve procedure . The most commonly used procedures were restrictive mitral valve annuloplasty ( MVP ) and MVR with a mechanical prosthesis . We collected all pertinent preoperative , intraoperative , and early-postoperative data . We followed up with phone interviews of the patients and their relatives and with complete clinical and echocardiography examinations . RESULTS We carried out operations on 138 patients during the study period ( MVR , 52 patients ; MVP , 86 patients ) . The 2 groups had comparable demographic data and risk factors . The 2 groups were significantly different with respect to mean ( + /-SD ) New York Heart Association ( NYHA ) class ( MVP , 2.72 + /- 0.62 ; MVR , 2.48 + /- 0.70 ; P < .01 ) and ejection fraction ( MVP , 29.01 % + /- 11.00 % ; MVR , 35.87 % + /- 11.00 % ; P < /= .01 ) . The 30-day mortality rates for the MVR and MVP groups were significantly different ( 9.61 % and 5.81 % , respectively ; P < .01 ) . Our follow-up included 83 % of the patients and continued for up to 84 months . The 2 groups showed no significant difference in mortality by the end of follow-up ; however , the MVR patients had a better ejection fraction ( 37.79 % versus 29.86 % ) and NYHA functional class ( 1.88 + /- 0.498 versus 2.36 + /- 0.564 ; P < .01 ) . CONCLUSION Correcting chronic IMR with either repair or replacement produces a good mid-term survival rate ( approximately 75 % ) for survivors in NYHA classes I and II . In our study , mortality rates for the MVP and MVR groups were similar , even though the repair group had a lower mean ejection fraction and a higher NYHA class before and after the operation . We therefore conclude that repair is superior to replacement in treating ischemic mitral insufficiency . A prospect i ve r and omized study is needed to better compare these 2 approaches Output:	Although MVR for ischaemic MR has a higher 30-day mortality rate compared with MVRp , MVRp is associated with the higher rate of MR recurrence and the need for reoperation . MVR remains an attractive option for ischaemic MR
MS21991	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND PURPOSE Telemedicine can disseminate vascular neurology expertise and optimize recombinant tissue plasminogen activator ( rt-PA ) use for acute ischemic stroke in rural underserved communities . The purpose of this study was to prospect ively assess whether telemedicine or telephone was superior for decision-making . METHODS The study design is a pooled analysis of two identically design ed r and omized controlled trials conducted in a multistate hub and spoke telestroke network setting with acute stroke syndrome patients , comparing telemedicine versus telephone-only consultations . From each trial , common data elements were pooled to assess , principally , for correctness of thrombolysis decision-making . Secondary outcomes included rt-PA use rate , 90-day functional outcome , post-thrombolysis intracranial hemorrhage , and data completeness . RESULTS Two hundred seventy-six pooled patients were evaluated . Correct thrombolysis eligibility decisions were made more often with telemedicine ( 96 % telemedicine , 83 % telephone ; odds ratio [ OR ] 4.2 ; 95 % confidence interval [ CI ] 1.69 - 10.46 ; p=0.002 ) . Intravenous rt-PA usage was 26 % ( 29 % telemedicine , 24 % telephone ; OR 1.27 ; 95 % CI 0.71 - 2.25 ; p=0.41 ) . Ninety-day outcomes were not different for Barthel Index , modified Rankin Scale , or mortality . There was no difference in post-thrombolysis intracranial hemorrhage ( 8 % telemedicine , 6 % telephone ; p>0.999 ) . CONCLUSIONS This pooled analysis supports the hypothesis that stroke telemedicine consultations , compared with telephone-only , result in more accurate decision-making . Together with high rt-PA utilization rate , low post-rt-PA intracranial hemorrhage rate , and acceptable patient outcome , the results confirm that telemedicine is a viable consultative tool for acute stroke . The replication of the hub and spoke network infrastructure supports the generalizability of telemedicine when used in broader setting Background and Purpose — Telestroke networks offer an opportunity to increase tissue-type plasminogen activator use in community hospitals . Methods — We compared 83 patients treated with intravenous tissue-type plasminogen activator by telestroke to 59 patients treated after in-person evaluation by the same neurologists at a tertiary care stroke center . Onset and door-to-treatment times and functional outcome at 90 days were obtained prospect ively . Favorable outcome was defined as modified Rankin Scale score ⩽2 . Results — Favorable outcome rates were comparable between the groups ( 42.1 % versus 37.5 % , P=0.7 ) . There was no significant difference in the rate of symptomatic hemorrhage . Conclusions — Telestroke is a viable alternative to in-person evaluation when stroke expertise is not readily available BACKGROUND Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke , but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established . We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke . METHODS After exclusion of patients with a brain hemorrhage or major infa rct ion , as detected on a computed tomographic scan , we r and omly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase ( 0.9 mg per kilogram of body weight ) or placebo . The primary end point was disability at 90 days , dichotomized as a favorable outcome ( a score of 0 or 1 on the modified Rankin scale , which has a range of 0 to 6 , with 0 indicating no symptoms at all and 6 indicating death ) or an unfavorable outcome ( a score of 2 to 6 on the modified Rankin scale ) . The secondary end point was a global outcome analysis of four neurologic and disability scores combined . Safety end points included death , symptomatic intracranial hemorrhage , and other serious adverse events . RESULTS We enrolled a total of 821 patients in the study and r and omly assigned 418 to the alteplase group and 403 to the placebo group . The median time for the administration of alteplase was 3 hours 59 minutes . More patients had a favorable outcome with alteplase than with placebo ( 52.4 % vs. 45.2 % ; odds ratio , 1.34 ; 95 % confidence interval [ CI ] , 1.02 to 1.76 ; P=0.04 ) . In the global analysis , the outcome was also improved with alteplase as compared with placebo ( odds ratio , 1.28 ; 95 % CI , 1.00 to 1.65 ; P<0.05 ) . The incidence of intracranial hemorrhage was higher with alteplase than with placebo ( for any intracranial hemorrhage , 27.0 % vs. 17.6 % ; P=0.001 ; for symptomatic intracranial hemorrhage , 2.4 % vs. 0.2 % ; P=0.008 ) . Mortality did not differ significantly between the alteplase and placebo groups ( 7.7 % and 8.4 % , respectively ; P=0.68 ) . There was no significant difference in the rate of other serious adverse events . CONCLUSIONS As compared with placebo , intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke ; alteplase was more frequently associated with symptomatic intracranial hemorrhage . ( Clinical Trials.gov number , NCT00153036 . Background : IV thrombolysis represents the most effective acute stroke therapy . However , it is almost exclusively performed in stroke centers and is not available in most community areas . The Telemedical Pilot Project for Integrative Stroke Care ( TEMPiS ) was started in February 2003 . Twelve community hospitals with no or very limited stroke thrombolysis experience and two stroke centers were connected via a network providing online neurologic examination and transfer of neuroradiologic scans . Following recently published preliminary results on acute phase safety of telethrombolysis , the present study reports on its long-term functional outcome . Methods : Modified Rankin Scale ( mRS ) , Barthel Index ( BI ) , and mortality rate were prospect ively collected 3 and 6 months after IV thrombolysis in patients of community network hospitals ( telemedical group ) and the stroke centers . Values of 95/100 for the BI and 0/1 for the mRS were defined as a favorable outcome . Results : Over the first 22 months , 170 patients were treated with tPA in the telemedical hospitals and 132 in the stroke center hospitals . Mortality rates were 11.2 % vs 11.5 % at 3 months ( p = 0.55 ) and 14.2 % vs 13 % at 6 months ( p = 0.45 ) . A good functional outcome after 6 months was found in 39.5 % of the telemedical hospitals vs 30.9 % of the stroke centers ( p = 0.10 ) for the mRS and 47.1 % vs 44.8 % ( p = 0.44 ) regarding the BI . Conclusions : Mortality rates and functional outcomes for telemedicine-linked community hospitals and stroke centers were similar and comparable to the results from r and omized trials Background and Purpose — Telemedicine techniques can be used to address the rural – metropolitan disparity in acute stroke care . The Stroke Team Remote Evaluation Using a Digital Observation Camera ( STRokE DOC ) trial reported more accurate decision making for telemedicine consultations compared with telephone-only and that the California-based research network facilitated a high rate of thrombolysis use , improved data collection , low risk of complications , low technical complications , and favorable assessment times . The main objective of the STRokE DOC Arizona TIME ( The Initial Mayo Clinic Experience ) trial was to determine the feasibility of establishing , de novo , a single-hub , multirural spoke hospital telestroke research network across a large geographical area in Arizona by replicating the STRokE DOC protocol . Methods — Methods included prospect i ve , single-hub , 2-spoke , r and omized , blinded , controlled trial of a 2-way , site-independent , audiovisual telemedicine system design ed for remote examination of adult patients with acute stroke versus telephone consultation to assess eligibility for treatment with intravenous thrombolysis . The primary outcome measure was whether the decision to give thrombolysis was correct . Secondary outcomes were rate of thrombolytic use , 90-day functional outcomes , incidence of intracerebral hemorrhages , and technical observations . Results — From December 2007 to October 2008 , 54 patients were assessed , 27 of whom were r and omized to each arm . Mean National Institutes of Health Stroke Scale score at presentation was 7.3 ( SD 6.2 ) points . No consultations were aborted ; however , technical problems ( 74 % ) were prevalent in the telemedicine arm . Overall , the correct treatment decision was established in 87 % of the consultations . Both modalities , telephone ( 89 % correct ) and telemedicine ( 85 % correct ) , performed well . Intravenous thrombolytic treatment was used in 30 % of the telemedicine and telephone consultations . Good functional outcomes at 90 days were not significantly different . There were no statistically significant differences in mortality ( 4 % in telemedicine and 11 % in telephone ) or rates of intracerebral hemorrhage ( 4 % in telemedicine and 0 % in telephone ) . Conclusions — It is feasible to extend the original STRokE DOC trial protocol to a new state and establish an operational single-hub , multispoke rural hospital telestroke research network in Arizona . The trial was not design ed to have sufficient power to detect a difference between the 2 consultative modes : telemedicine and telephone-only . Whether by telemedicine or telephone consultative modalities , there were appropriate treatment decisions , high rates of thrombolysis use , improved data collection , low rates of intracerebral hemorrhage , and equally favorable time requirements . The learning curve was steep for the hub and spoke personnel of the new telestroke network , as reflected by frequent technical problems . Overall , the results support the effectiveness of highly organized and structured stroke telemedicine networks for extending expert stroke care into rural remote communities lacking sufficient neurological expertise Background and Purpose — Systemic thrombolysis is the only therapy proven to be effective for ischemic stroke . Telemedicine may help to extend its use . However , concerns remain whether management and safety of tissue plasminogen activator ( tPA ) administration after telemedical consultation are equivalent in less experienced hospitals compared with tPA administration in academic stroke centers . Methods — During the second year of the ongoing Telemedical Pilot Project for Integrative Stroke Care , all systemic thrombolyses in stroke patients of the 12 regional clinics and the 2 stroke centers were recorded prospect ively . Patients ’ demographics , stroke severity ( National Institutes of Health Stroke Scale ) , frequency of administration , time management , protocol violations , and safety were included in the analysis . Results — In 2004 , 115 of 4727 stroke or transient ischemic attack patients ( 2.4 % ) in the community hospitals and 110 of 1889 patients in the stroke centers ( 5.8 % ) received systemic thrombolysis . Prehospital latencies were shorter in the regional hospitals despite longer distances . Door to needle times were shorter in the stroke centers . Although blood pressure was controlled more strictly in community hospitals , symptomatic intracerebral hemorrhage rate ( 7.8 % ) was higher ( P=0.14 ) than in stroke centers ( 2.7 % ) but still within the range of the National Institute of Neurological Disorders and Stroke trial . In-hospital mortality rate was low in community hospitals ( 3.5 % ) and in stroke centers ( 4.5 % ) . Conclusions — Although with a lower rate of systemic thrombolysis , there was no evidence of lower treatment quality in the remote hospitals . With increasing numbers of tPA administration and growing training effects , the telestroke concept promises better coverage of systemic thrombolysis in nonurban areas Background and Purpose — In acute stroke care , rapid but careful evaluation of patients is m and atory but requires an experienced stroke neurologist . Telemedicine offers the possibility of bringing such expertise quickly to more patients . This study tested for the first time whether remote video examination is feasible and reliable when applied in emergency stroke care using the National Institutes of Health Stroke Scale ( NIHSS ) . Methods — We used a novel multimedia telesupport system for transfer of real-time video sequences and audio data . The remote examiner could direct the set-top camera and zoom from distant overviews to close-ups from the personal computer in his office . Acute stroke patients admitted to our stroke unit were examined on admission in the emergency room . St and ardized examination was performed by use of the NIHSS ( German version ) via telemedicine and compared with bedside application . Results — In this pilot study , 41 patients were examined . Total examination time was 11.4 minutes on average ( range , 8 to 18 minutes ) . None of the examinations had to be stopped or interrupted for technical reasons , although minor problems ( brightness , audio quality ) with influence on the examination process occurred in 2 sessions . Unweighted & kgr ; coefficients ranged from 0.44 to 0.89 ; weight Output:	Conclusions : Our findings indicate that IV tPA delivery through telestroke networks is safe and effective in the 3-hour time window .
MS21992	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE The Comparison of Ophthalmic Medications for Tolerability ( COMTOL ) question naire was developed for use in clinical trials to compare the tolerability of topical ophthalmic medications used in the treatment of glaucoma . The question naire captures the frequency and bother of common side effects ( i.e. , ocular and other local effects , and effects on visual function ) of topical therapy for lowering intraocular pressure . In addition , the question naire measures the extent to which these side effects and any associated limitations in routine living activities interfere with health-related quality of life , medication compliance , and patient satisfaction with the medication . This study was design ed to assess the measurement characteristics of the COMTOL question naire . METHODS The internal consistency , reliability , reproducibility , construct validity , discriminant validity , and responsiveness of the question naire were assessed in 70 adult patients with glaucoma in a clinical trial comparing timolol and pilocarpine . RESULTS The question naire showed good-to-excellent internal consistency ( 0.73 to 0.98 ) , reliability ( 0.76 to 0.94 ) , and reproducibility ( 0.75 to 0.93 ) . In general , there was a strong correlation in the expected direction between the frequency and bother of side effects and patient-perceived global measures . The question naire discriminated between patients receiving timolol and patients receiving pilocarpine . The question naire demonstrated significant responsiveness to change . CONCLUSIONS The COMTOL question naire showed acceptable measurement characteristics for inclusion as a tolerability measure to supplement spontaneous adverse event reporting in clinical trials of topical ophthalmic therapy The relationship between adherence to highly active antiretroviral therapy ( HAART ) and RNA-HIV viral load outcomes has been extensively shown . Although there are different procedures for assessing treatment adherence , there is no ideal method . We present the SERAD ( Self-Reported Adherence ) question naire , a qualitative and quantitative self-reported instrument design ed to provide an easier adherence measurement . We also compared the question naire to three other methods to evaluate adherence to HAART regimens in HIV-infected patients . Two prospect i ve , observational , longitudinal studies were developed : a single-center pilot study followed by a multicenter study . A total of 530 HIV-infected out patients was prospect ively included , 66 in the pilot study and 464 in the multicenter study . Four methods were used to study adherence to HAART regimens : the SERAD question naire , pill count , electronic monitoring , and plasma drug monitoring . Pearson 's correlations and Bl and and Altman 's method were developed . The SERAD question naire showed good feasibility and significant validity . Adequate levels of agreement between methods were observed , particularly when adherence was high . Differences increased as adherence fell . Moreover , the question naire was completed correctly , the interviewers did not report uncovered aspects , and the information was collected easily . Our results suggest that the SERAD question naire is a feasible and useful instrument for assessing adherence to HAART regimens in HIV-infected patients , and makes it possible to obtain reliable qualitative and quantitative information related to treatment adherence Nonadherence to immunosuppressants in renal transplant recipients is a major factor affecting graft survival , but it is difficult to detect accurately in clinical practice . Adherence was measured in 153 adult renal transplant recipients using self-report question naires and interview , clinician rating , and cyclosporine levels . The sensitivity and specificity of these measures were determined by comparison with electronic monitoring in a r and omly selected sub sample of 58 subjects . Measures of adherence in current clinical use do not perform well when tested against electronic monitoring . Self-report at a confidential interview was the best measure of adherence for the detection of both missed doses and erratic timing of medication . However , the use of a confidential interview is not directly applicable to a clinical setting . Further research on how best to facilitate disclosure in clinical setting s may be the best way to develop adherence measures for use in routine practice The Hill-Bone Compliance to High Blood Pressure Therapy Scale assesses patient behaviors for three important behavioral domains of high blood pressure treatment : 1 ) reduced sodium intake ; 2 ) appointment keeping ; and 3 ) medication taking . This scale is comprised of 14 items in three subscales . Each item is a four point Likert type scale . The content validity of the scale was assessed by a relevant literature review and an expert panel , which focused on cultural sensitivity and appropriateness of the instrument for low literacy . Internal consistency reliability and predictive validity of the scale were evaluated using two community based sample s of hypertensive adults enrolled in clinical trials of high blood pressure care and control . The st and ardized alpha for the total scale were 0.74 and 0.84 , and the average interitem correlations of the 14 items were 0.18 and 0.28 , respectively . The construct and predictive validity of the scale was assessed by factor analysis and by testing of theoretically derived hypotheses regarding whether the scale demonstrated consistent and expected relationships with related variables . In this study , high compliance scale scores predicted significantly lower levels of blood pressure and blood pressure control . Moreover , high compliance scale scores at the baseline were significantly associated with blood pressure control at both baseline and at follow up in the two independent sample s. This brief instrument provides a simple method for clinicians in various setting s to use to assess patients ' self reported compliance levels and to plan appropriate interventions Objectives Many question naires on adherence to antiretroviral therapy are in use , but the validity of patients ’ responses has not been tested . The Medication Adherence Self-Report Inventory ( MASRI ) has been developed and tested for its validity against objective measures and treatment outcome . Design Prospect i ve study comparing question naire responses with MEMS TrackCap ( MC , a medication event monitoring system ) , pill count ( PC ) and plasma HIV viraemia in a publicly funded specialist HIV clinic . Participants Patients self-medicating antiretroviral therapy who were not cognitively impaired and were able to read and underst and English . Results Mean adherence by MC of the 78 subjects was 92.9 % ( SE , 1.8 % ) and by PC 96.8 % ( SE , 1.4 % ) . Agreement between MC and responses to items about doses missed 1 , 2 or 3 days ago was low ( κ = 0.23 ( P < 0.03 ) , 0.44 ( P < 0.001 ) and 0.28 ( P < 0.01 ) respectively ) . This improved when these responses were summated ( κ = 0.46;P < 0.001 ) and was similar to that for recall of non-adherence over the preceding 2 weeks ( κ = 0.54;P < 0.001 ) . Mean self-reported adherence by visual analogue scale ( VAS ) over the preceding month was 93.3 % ( SE , 1.2 % ) . This was strongly associated with both MC ( r = 0.63;P < 0.001 ) and PC ( r = 0.75;P < 0.001 ) . On multivariate analysis , the strongest association between a MASRI item and MC was for the VAS . Both the 2 week recall and VAS items were inversely associated with viral load ( P = 0.01 ) . There was no association between dose timing ( measured MC or question naire ) or 3 day self-report and viral load . Conclusions The MASRI provides a means of measuring patient adherence that is valid when compared with objective measures In this prospect i ve study we compared the incidence of late acute rejections ( LAR ) and changes in serum‐creatinine over time between compliers and noncompliers with immunosuppressive therapy more than 1 year post transplantation and explored the relative contribution of non‐compliance and other risk factors in the occurrence of LAR Background . Renal transplant recipients regularly fail to take their prescribed immunosuppressive medications , frequently leading to adverse outcomes . Methods . Medication vials incorporating electronic monitor circuits in their caps compiled prospect i ve data files on the azathioprine dosing patterns of 180 adult renal transplant recipients monitored up to 4 years . These patients were followed for a mean of 8.7 years posttransplantation . Results . Patients were divided into three groups by the medication doses missed during the first 6 months posttransplant . These initial dosing patterns remained remarkably consistent up to 4 years . Patients ( n=47 ) missing the most doses ( ≥5 % ) experienced earlier and more frequent acute rejection episodes ( P=0.025 ) . This group also demonstrated significantly longer interdose intervals ( P=0.005 ) , with more frequent ( P<0.001 ) and longer ( P<0.001 ) “ drug holidays . ” A patient subgroup with early declining medication adherence ( n=23 ) experienced dramatically poorer outcomes , with significantly increased acute rejection ( P<0.001 ) , chronic rejection ( P=0.034 ) , graft loss before death ( P<0.001 ) , and death ( P=0.04 ) . In all tertiles there was a trend toward missing more medication over time . Conclusions . Excellent posttransplant medication adherence is critical to improved outcomes . Individual dosing patterns are established early after hospital discharge and remain remarkably consistent , despite gradual erosion in adherence over time . The later consequences of medication nonadherence , especially early declines in adherence , include increased frequencies of rejection , graft loss , and death BACKGROUND Poor medical compliance has been held responsible for a large proportion of deaths occurring subsequent to initial postoperative recovery . However , beyond clinical reports , there has been little empirical examination of this issue , or of the extent to which major psychiatric disorder and failure to adjust to the transplant predict long-term physical morbidity and mortality . We prospect ively examined whether a full range of compliance behaviors and psychiatric outcomes during the first year post-transplant predicted subsequent mortality and physical morbidity through 3 years post-transplant . METHODS A total of 145 heart recipients who had received detailed compliance and mental health assessment s during the first year post-transplant were followed up at 3 years post-transplant . Interview data and corroborative information from family members were used to determine compliance in multiple domains , psychiatric diagnoses , and psychiatric symptomatology during the first year post-surgery . Medical record review s were performed to abstract data on acute graft rejection episodes , incident cardiac allograft disease ( CAD ) and mortality from 1 to 3 years post-transplant . RESULTS After controlling for known transplant-related predictors of outcome , multivariate analyses yielded the following significant ( p < 0.05 ) results : ( a ) risk of acute graft rejection was 4.17 times greater among recipients who were not compliant with medications ; ( b ) risk of incident CAD was elevated by persistent depression ( Odds Ratio , OR = 4.67 ) , persistent anger-hostility ( OR = 8.00 ) , medication noncompliance ( OR = 6.91 ) , and obesity ( OR = 9.92 ) ; and ( c ) risk of mortality was increased if recipients met criteria for Post-Traumatic Stress Disorder related to the transplant ( OR = 13.74 ) . CONCLUSIONS The findings , plus data we have previously reported that showed which patients are most likely to have compliance and psychiatric problems early post-transplant , suggest that interventions focused on maximizing patients ' psychosocial status in these areas may further improve long-term physical health outcomes in this population The aim of this study was to verify the validity of a new self-reported question naire design ed to assess nonadherence to antiretroviral medication among patients with HIV . Two hundred fifty-six patients from four clinics participated in a prospect i ve longitudinal study . The question naire was design ed to measure if patients with HIV were taking less than the total number of antiretroviral pills prescribed by their physician . Change in viral load was used as the criterion for validity analyses . Self-reported adherence , viral load and CD4 cell count were assessed at T0 ( baseline ) , T3 ( 3-month ) , and T6 ( 6-month ) . The findings indicated that the question naire had adequate validity ( sensitivity , 71 % ; specificity , 72 % ; correct classification , 72 % ; odd ratio , 6.15 ) . These best values were obtained when the analyses excluded individuals with an unstable viral load and a CD4 cell count of less than 200 copies per milliliter over the 6-month follow-up period . This study has shown that this question naire has satisfactory psychometric qualities to assess nonadherence to antiretroviral medication among patients with HIV . The question naire is brief , simple , and can be used in both clinical or research setting s regardless of the patients ' antiretroviral regimens Nonadherence to antiretroviral therapy is a substantial problem in HIV and jeopardizes the success of treatment . Accurate measurement of nonadherence is therefore imperative for good clinical management but no gold st and ard has been agreed on yet . In a single-center prospect i ve study nonadherence was assessed by electronic monitoring : percentage of doses missed and drug holidays and by three self reports : ( 1 ) a visual analogue scale ( VAS ) : percentage of overall doses taken ; ( 2 ) the Swiss HIV Cohort Study Adherence Question naire ( SHCS-AQ ) : percentage of overall doses missed and drug holidays and ( 3 ) the European HIV Treatment Question naire ( EHTQ ) : percentage of doses missed and drug holidays for each antiretroviral drug separately . Virologic failure prospect ively assessed during 1 year , and electronic monitoring were used as reference st and ards . Using virologic failure as reference st and ard , the best results were for ( 1 ) the SH Output:	DISCUSSION The three selected self-report scales may assist transplant professionals in detecting nonadherence . However , these scales were only vali date d in patients with HIV .
MS21993	*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 GOAL : To compare the efficacy and safety of single 1 g oral azithromycin with doxycycline , 100 mg twice daily for seven days for treatment of uncomplicated urogenital chlamydial infection . STUDY DESIGN : R and omised , unblinded , comparative trial , involving 597 patients demonstrating clinical evidence of genital chlamydia and a positive non-culture assay for Chlamydia trachomatis . RESULTS : Among the azithromycin- and doxycycline-treated patients 61 % and 60 % , respectively , were asymptomatic within one week after the first dose . At two weeks , these figures increased to 86 % and 83 % , respectively . Bacteriological eradication , based on a negative assay , occurred in 338 ( 97 % ) of 347 azithromycin-treated patients and 161 ( 99 % ) of 163 doxycycline-treated patients . CONCLUSION : Treatment of uncomplicated chlamydial cervicitis and urethritis with single 1 g oral azithromycin is equivalent to st and ard therapy with doxycycline . Drug-related adverse events were approximately twice as common as previously reported for both drugs Aims : To identify any differences in follow-up rates or sexual contact attendance rates in men presenting with non-gonococcal urethritis ( NGU ) after treatment by single dose azithromycin rather than longer st and ard duration therapies and to identify patients ' treatment preferences . Methods : A prospect i ve study was performed on 200 consecutive men attending a genito-urinary medicine ( GUM ) clinic with new episode , microscopically confirmed NGU . The first 100 patients were treated with st and ard duration therapy ( Group S ) whilst the second 100 patients received a single 1 g oral dose of azithromycin ( Group A ) . Patient-led contact tracing was arranged and patients were asked to return for review when a test of cure was performed , contact attendance noted and the patient 's treatment preference ascertained . Results : Both groups were predominantly heterosexual and over 60 % gave a history of previous sexually transmitted disease ( STD ) . There were no significant differences in efficacy between Groups S and A. However , the index follow-up rate and percentage of traceable sexual contacts attending was higher in Group A. In both groups contacts of homosexual men were more likely to attend the GUM clinic . More additional visits were made by Group S due to mislaid medication or compliance problems . Over 70 % of patients question ed expressed a preference for single dose therapy . Conclusion : Single dose therapy with 1 g of azithromycin is as efficacious as longer duration therapies with advantages in patient follow-up rates and contact attendance and for the majority of patients would be their treatment of choice . A cost analysis supports the practical application of this regimen & NA ; Pivampicillin and doxycycline were compared in the treatment of chlamydial urethritis in 80 heterosexual men . The trial was carried out in a double‐blind , comparative parallel group fashion . Forty patients were treated with 700 mg of pivampicillin twice daily and another 40 with 200 mg of doxycycline on the first day and thereafter with 100 mg of doxycycline and one placebo tablet daily . Both treatments lasted for 9 days . Follow‐up examinations were carried out 2 weeks ( 14‐16 days ) and 4 weeks ( 26‐30 days ) after the start of treatment . Altogether five ( 12.5 % ) of the forty pivampicillin‐treated patients were clinical failures and three ( 7.5 % ) still harbored Chlamydia trachomatis after treatment . The corresponding figures for the doxycycline‐treated patients were two ( 5.1 % ) and one ( 2.6 % ) . The difference between the treatment results of the two groups did not reach statistical significance Two-hundred patients with confirmed Chlamydia trachomatis infection of the urogenital region were treated with either ciprofloxacin 1.5 g/day or doxycycline 100 mg/day for seven days . One-hundred and fifty-seven patients were males and 43 females . C. trachomatis was isolated prior to treatment from urethra alone in 155 patients , from cervix alone in 27 and from both urethra and cervix in 15 . The first re-examination was carried out at the end of treatment and the second one week later . Six patients in the ciprofloxacin group and three in the doxycycline group never returned for the first re-examination . At the second re-examination there were seven defaulters in the ciprofloxacin group and 11 in the doxycycline group . Altogether there were 12 bacteriological failures in both groups . Clinical failure despite bacteriological cure occurred in 20 patients in the ciprofloxacin group and eight in the doxycycline group . The total number of treatment failures was 32 in the ciprofloxacin group and 20 in the doxycycline group . The results suggested that neither treatment was efficient enough in the treatment of uncomplicated urogenital infections caused by C. trachomatis The effect of doxycycline treatment was studied in 46 men with chlamydial non-gonococcal urethritis . Treatment with 200 mg doxycycline daily for 10 days rendered 22 of 22 patients free of urethritis . The treatment had no effect on the complications of urethritis like prostatitis and Reiter 's syndrome . In the other group where 200 mg doxycycline was given on the first day and 100 mg on the subsequent days for 8 days , urethritis was resolved in 18 of 22 patients . C. trachomatis was not re-isolated from any of the patients after doxycycline treatment We compared a single 1 gm dose of azithromycin with the st and ard 7-day course of doxycycline for the treatment of uncomplicated chlamydial genital infection in sexually active adolescents . Seventy-three adolescents ( 65 female ) with a cervical or urethral culture positive for Chlamydia trachomatis were enrolled in the study ; 46 received azithromycin and 27 received doxycycline . Follow-up evaluations were done 1 , 2 , and 4 weeks after treatment with azithromycin or initiation of treatment with doxycycline . There were four treatment failures ( 8.7 % ) among the patients who received azithromycin and four in the doxycycline-treated group ( 14.8 % ) ; all were female . Six of these girls ( three treated with azithromycin and three with doxycycline ) gave histories of unprotected intercourse with an untreated partner and were probably reinfected . Almost half the patients were clinical ly symptom free . The clinical response rate for the remaining patients with symptoms was 97.4 % at 4 weeks . Nineteen percent of the azithromycin-treated patients and 33.3 % of those treated with doxycycline had mild to moderate drug-related side effects , which were predominantly gastrointestinal . We conclude that treatment with a single oral dose of azithromycin appears to be as safe and efficacious as a 7-day course of doxycycline for the treatment of uncomplicated genital chlamydial infection in adolescents A total of 2124 women who attended the Richmond Family Planning Association Clinic in Melbourne consecutively were screened for the presence or absence of Chlamydia trachomatis . One hundred and three women were found to have Chl . trachomatis infection of the cervix and were invited to participate in a clinical trial of minocycline and doxycycline for the treatment of chlamydial infection . A 10-day course of either drug result ed in a negative result of a chlamydial culture for all patients at the follow-up assessment , which occurred between 11 days to 12 weeks after the therapy . Minocycline and doxycycline showed equal effectiveness in the eradication of mycoplasmas in over 80 % of the treated patients . Minocycline appeared to have a slight advantage with respect to the resolution of the gynaecological symptoms that were associated with the chlamydial infection . The number of adverse events that were recorded during the trial was similar for both treatment regimens . Gynaecological symptoms were associated with chlamydial infection in approximately 50 % of the women in the study . The lack of association between chlamydial infection and gynaecological symptoms has led to the instigation of routine testing for the presence of Chlamydia spp . in young women who have more than one sexual partner OBJECTIVES The heterosexual spread of HIV-1 is occurring at different rates in different parts of the world . The transmission probability of HIV-1 per sexual contact is low , but may be greatly enhanced by several cofactors . Sexually transmitted diseases ( STD ) , especially genital ulcers , may be such factors . So far , epidemiological evidence that other STD facilitate HIV-1 transmission is weak . The objective of this study was to determine whether treatable STD enhanced sexual transmission of HIV-1 in a cohort of female prostitutes in Kinshasa , Zaire . METHODS We conducted a nested case-control study of 431 initially HIV-1-negative women followed prospect ively for a mean duration of 2 years ( with monthly STD check-ups and 3-monthly HIV-1 serology ) . Cases ( seroconverters , n = 68 ) were compared with controls ( women who remained HIV-1-negative , n = 126 ) for incidence of STD and sexual exposure during the presumed period of HIV-1 acquisition . RESULTS The annual incidence of HIV-1 in this cohort was 9.8 % . Seroconverters were younger than HIV-1-negative women ( mean age , 24.6 versus 26.8 years ; P = 0.04 ) . During the period of HIV-1 acquisition , cases had a much higher incidence of gonorrhoea , chlamydial infection and trichomoniasis , and engaged in unprotected sex with clients and partners more frequently than controls . After controlling for sexual exposure by multivariate analysis , adjusted odds ratios for seroconversion were 4.8 [ 95 % confidence interval ( CI ) , 2.4 - 9.8 ] for gonorrhoea , 3.6 ( 95 % CI , 1.4 - 9.1 ) for chlamydial infection and 1.9 ( 95 % CI , 0.9 - 4.1 ) for trichomoniasis . Genital ulcers were more frequent in cases than controls , but much less common than other STD . CONCLUSION Non-ulcerative STD were risk factors for sexual transmission of HIV-1 in women , after controlling for sexual exposure . Because of their high prevalence in some population s , non-ulcerative STD may represent a considerable population -attributable risk in the transmission of HIV-1 worldwide . The identification of treatable STD as risk factors for HIV-1 transmission offers an important additional strategy for the prevention of HIV/AIDS CONTEXT Adolescents are at highest risk for infection with Chlamydia trachomatis , an important preventable cause of pelvic inflammatory disease and subsequent tubal factor infertility in US women . Current guidelines for delivery of adolescent primary care services recommend yearly chlamydia screening for those adolescent females considered to be at risk . OBJECTIVES To describe the epidemiology of prevalent and incident chlamydia infection among adolescent females to assess the appropriate interval for chlamydia screening and to define risk factors that would identify adolescent females to target for screening . DESIGN Prospect i ve longitudinal study . PATIENTS A consecutive sample of 3202 sexually active females 12 through 19 years old making 5360 patient visits over a 33-month period , January 1994 through September 1996 . SETTING Baltimore , Md , family planning , sexually transmitted disease , and school-based clinics . INTERVENTION Testing for C trachomatis by polymerase chain reaction . MAIN OUTCOME MEASURES Prevalence and incidence of C trachomatis infections ; predictors of positive test result for C trachomatis . RESULTS Chlamydia infection was found in 771 first visits ( 24.1 % ) and 299 repeat visits ( 13.9 % ) ; 933 adolescent females ( 29.1 % ) had at least 1 positive test result . Females who were 14 years old had the highest age-specific chlamydia prevalence rate ( 63 [ 27.5 % ] of 229 cases ; P=.01 ) . The chlamydia incidence rate was 28.0 cases per 1000 person-months ( 95 % confidence interval , 24.9 - 31.5 cases ) . The median time was 7.2 months to a first positive chlamydia test result and 6.3 months to a repeat positive test result among those with repeat visits . Independent predictors of chlamydia infection -- reason for clinic visit , clinic type , prior sexually transmitted diseases , multiple or new partners , or inconsistent condom use-failed to identify a subset of adolescent females with the majority of infections . CONCLUSIONS A high prevalence and incidence of C trachomatis infection were found among adolescent females . We , therefore , recommend screening all sexually active adolescent females for chlamydia infection every 6 months , regardless of symptoms , prior infections , condom use , or multiple partner risks BACKGROUND AND OBJECT Output:	Azithromycin and doxycycline are equally efficacious in achieving microbial cure and have similar tolerability .
MS21994	*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 African American men with hypertension in low socioeconomic urban population s achieve poor rates of hypertension control and suffer early from its complications . METHODS In a r and omized clinical trial with 309 hypertensive urban African American men aged 21 to 54 years , we evaluated the effectiveness of a more intensive comprehensive educational-behavioral-pharmacologic intervention by a nurse practitioner-community health worker-physician ( NP/CHW/MD ) team and a less intensive education and referral intervention in controlling blood pressure ( BP ) and minimizing progression of left ventricular hypertrophy ( LVH ) and renal insufficiency . Changes in BP , left ventricular mass ( LVM ) , and serum creatinine from baseline to 36 months were compared between groups . RESULTS At 36 months , the mean systolic BP/diastolic BP change from baseline was -7.5/-10.1 mm Hg for the more intensive group and + 3.4/-3.7 mm Hg for the less intensive group ( P = .001 and .005 for between-group differences in systolic BP and diastolic BP , respectively ) . The proportion of men with controlled BP ( < 140/90 mm Hg ) was 44 % in the more intensive group and 31 % in the less intensive group ( P = .045 ) . The LVM was significantly lower in the more intensive group than in the less intensive group ( more intensive , 274 g ; less intensive , 311 g ; P = .004 ) . There was a trend toward slowing of the progression of renal insufficiency ( incidence of 50 % increase in serum creatinine ) in the more intensive group compared to the less intensive group ( more intensive , 5.2 % ; less intensive , 8.0 % ; P = .08 ) . CONCLUSIONS During 36 months , the more intensive intervention led to a lower BP and decreased progression of LVH in a sample of hypertensive young African American men Background — Secondary prevention by risk factor modification improves patient outcomes , yet it is often not achieved in clinical practice . Reasons for failure stem from challenges of prioritizing risk factor reduction and engaging patients in changing their behaviors . We hypothesize that a novel telemedicine intervention with tailored patient education could improve cardiovascular risk factors . Methods — To evaluate this intervention , we propose enrolling 450 patients with a recent myocardial infa rct ion and hypertension into a 3-arm r and omized , controlled trial . The first arm ( n=150 ) will receive home blood pressure ( BP ) monitors plus a nurse-delivered , telephone-based tailored patient education intervention and will be enrolled into HealthVault , a Microsoft electronic health record platform . The second arm ( n=150 ) will also receive BP monitors plus a tailored patient education intervention and be enrolled in HeartVault . However , the patient education intervention will be delivered by a Web-based program and will cover topics identical to those in the nurse-delivered intervention . Both arms will be compared with a control group receiving st and ard care ( n=150 ) . All participants will have an in-person assessment at baseline and at completion of the study , including st and ardized measurements of BP , LDL cholesterol , and glycosylated hemoglobin ( in diabetic subjects ) . The study design will allow assessment of a telephone-based , nurse-administered disease management program versus st and ard care . The main outcome of interest is the reduction in systolic BP in each intervention group compared with the control group at 12 months . Secondary outcomes assessed will include reductions in LDL cholesterol , body weight , and glycosylated hemoglobin , as well as adherence to evidence -based therapies and improvement in health behaviors . Conclusion — If successful in optimizing BP control , managing other coronary heart disease risk factors , and demonstrating a lower cost , the Web-based disease management tool has the potential to enhance coronary artery disease management , quality of care , and ultimately , patient outcomes . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00901277 OBJECTIVE : To evaluate the effectiveness of a community pharmacist-based home blood pressure ( BP ) monitoring program . DESIGN : Trial of a high-intensity ( HI ) versus low-intensity ( LI ) intervention r and omized in 12 community pharmacies . The HI intervention comprised 4 face-to-face visits with a trained pharmacist . Pharmacists provided patient-specific education about hypertension . Following the first and third visits , patients were provided with a home BP monitoring device and instructed to measure their BP at least once daily for the next month . Home BP readings were used by the pharmacists to develop treatment recommendations for the patient ’s physician . Recommendations were discussed with the physician and , if approved , implemented by the pharmacist . In the LI intervention , pharmacists measured patients BP in the pharmacy and referred them to their physician for evaluation . PARTICIPANTS : Patients with uncontrolled BP at baseline . MEASUREMENTS : The main outcomes were the differences in systolic and diastolic BP ( SBP and DBP ) from baseline to follow-up between the HI and LI patients . RESULTS : The study enrolled 125 patients , 64 in the HI and 61 in the LI group . From baseline , SBP declined 13.4 mmHg in the HI group and 9.0 mmHg in the LI group . At the final visit , the difference in SBP/DBP change between the HI and LI group was −4.5/−3.2 mmHg ( P=.12 for SBP and P=.03 for DBP ) . CONCLUSIONS : The HI intervention achieved a lower DBP and this model could be a strategy for patients with hypertension OBJECTIVE To compare the effectiveness of an evidence -based , systematic approach to hypertension care involving comanagement of patients by primary care physicians and clinical pharmacists versus usual care in reducing blood pressure in patients with uncontrolled hypertension . METHODS Patients in a staff model medical group with uncontrolled hypertension were r and omized to either a usual care ( UC ) or a physician-pharmacist comanagement ( PPCM ) group . All physicians in the study received both group and individual education and participated in the development of an evidence -based hypertension treatment algorithm . Physicians were then given the names of their patients whose medical records documented elevated blood pressures ( defined as systolic > or = 140 mm Hg and /or diastolic > or = 90 mm Hg for patients aged < 65 yrs , and systolic > or = 160 mm Hg and /or diastolic > or = 90 mm Hg for those aged > or = 65 yrs ) . Patients r and omized to the UC group were managed by primary care physicians alone . Those r and omized to the PPCM group were comanaged by their primary care physician and a clinical pharmacist , who provided patient education , made treatment recommendations , and provided follow-up . Blood pressure measurements , antihypertensive drugs , and visit costs/patient were obtained from medical records . RESULTS One hundred ninety-seven patients with uncontrolled hypertension participated in the study . Both PPCM and UC groups experienced significant reductions in blood pressure ( systolic -22 and -11 mm Hg , respectively , p < 0.01 ; diastolic -7 and -8 mm Hg , respectively , p < 0.01 ) . The reduction in systolic blood pressure was greater in the PPCM group after adjusting for differences in baseline blood pressure between the groups ( p < 0.01 ) . More patients achieved blood pressure control in the PPCM than in the UC group ( 60 % vs 43 % , p = 0.02 ) . Average provider visit costs/patient were higher in the UC than the PPCM group ( $ 195 vs $ 160 , p = 0.02 ) . CONCLUSIONS An evidence -based , systematic approach using physician-pharmacist comanagement for patients with uncontrolled hypertension result ed in improved blood pressure control and reduced average visit costs/patient BACKGROUND St and ard office-based approaches to controlling hypertension show limited success . Such suboptimal hypertension control reflects in part the absence of both an infrastructure for patient education and frequent , regular blood pressure ( BP ) monitoring . We tested the efficacy of a physician-directed , nurse-managed , home-based system for hypertension management with st and ardized algorithms to modulate drug therapy , based on patients ' reports of home BP . METHODS We r and omized out patients requiring drug therapy for hypertension according to the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) criteria to receive usual medical care only ( UC , n = 76 ) or usual care plus nurse care management intervention ( INT , n = 74 ) over a 6-month period . RESULTS Patients receiving INT achieved greater reductions in office BP values at 6 months than those receiving UC : 14.2 + /- 18.1 versus 5.7 + /- 18.7 mm Hg systolic ( P < .01 ) and 6.5 + /- 10.0 versus 3.4 + /- 7.9 mm Hg diastolic , respectively ( P < .05 ) . At 6 months , we observed one or more changes in drug therapy in 97 % of INT patients versus 43 % of UC patients , and 70 % of INT patients received two or more drugs versus 46 % of UC . Average daily adherence to medication , measured by electronic drug event monitors , was superior among INT subjects ( mean + /- SD , 80.5 % + /- 23.0 % ) than among UC subjects ( 69.2 + /- 31.1 % ; t(113 ) = 2.199 , P = .03 ) . There were no significant adverse drug reactions in either group . CONCLUSIONS Telephone-mediated nurse management can successfully address many of the systems-related and patient-related issues that limit pharmacotherapeutic effectiveness for hypertension BACKGROUND Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions who experience barriers to access to care or a high burden of illness . METHODS The authors conducted a r and omized , controlled trial comparing telemedicine case management to usual care , with blinding of those obtaining outcome data , in 1,665 Medicare recipients with diabetes , aged 55 years or greater , and living in federally design ated medically underserved areas of New York State . The primary endpoints were HgbA1c , blood pressure , and low-density lipoprotein ( LDL ) cholesterol levels . RESULTS In the intervention group ( n = 844 ) , mean HgbA1c improved over one year from 7.35 % to 6.97 % and from 8.35 % to 7.42 % in the subgroup with baseline HgbA1c > or = 7 % ( n = 353 ) . In the usual care group ( n = 821 ) mean HgbA1c improved over one year from 7.42 % to 7.17 % . Adjusted net reductions ( one-year minus baseline mean values in each group , compared between groups ) favoring the intervention were as follows : HgbA1c , 0.18 % ( p = 0.006 ) , systolic and diastolic blood pressure , 3.4 ( p = 0.001 ) and 1.9 mm Hg ( p < 0.001 ) , and LDL cholesterol , 9.5 mg/dL ( p < 0.001 ) . In the subgroup with baseline HgbA1c > or = 7 % , net adjusted reduction in HgbA1c favoring the intervention group was 0.32 % ( p = 0.002 ) . Mean LDL cholesterol level in the intervention group at one year was 95.7 mg/dL. The intervention effects were similar in magnitude in the subgroups living in New York City and upstate New York . CONCLUSION Telemedicine case management improved glycemic control , blood pressure levels , and total and LDL cholesterol levels at one year of follow-up BACKGROUND A patient-centered medical home ( PCMH ) demonstration was undertaken at 1 healthcare system , with the goals of improving patient experience , lessening staff burnout , improving quality , and reducing downstream costs . Five design principles guided development of the PCMH changes to staffing , scheduling , point-of-care , outreach , and management . OBJECTIVE To report differences in patient experience , staff burnout , quality , utilization , and costs in the first year of the PCMH demonstration . STUDY DESIGN Prospect i ve before and after evaluation . METHODS Baseline ( 2006 ) and 12-month ( 2007 ) measures were compared . Patient and staff experiences were measured using surveys from a r and om sample of patients and all staff at the PCMH and 2 control clinics . Automated data were used to measure and compare change components , quality , utilization , and costs for PCMH enrollees versus enrollees at 19 other clinics . Analyses included multivariate regressions for the different outcomes to account for baseline case mix . RESULTS After adjusting for baseline , PCMH patients reported higher ratings than controls on 6 of 7 patient experience scales . For staff burnout , 10 % of PCMH staff reported high emotional exhaustion at 12 months compared with 30 % of controls , despite similar rates at baseline . PCMH patients also had gains in composite quality between 1.2 % and 1.6 % greater than those of other patients Output:	These findings have been demonstrated in several meta-analyses and systematic review s. These review s have generally found that team-based care can reduce systolic blood pressure by 4 - 10 mm Hg over usual care . Few cost-effectiveness analyses have been performed but generally have found favorable costs for team-based care when considering the potential to reduce morbidity and mortality .
MS21995	*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 dietary protein intake higher than the Recommended Dietary Allowance during an energy deficit helps to preserve lean body mass ( LBM ) , particularly when combined with exercise . OBJECTIVE The purpose of this study was to conduct a proof-of-principle trial to test whether manipulation of dietary protein intake during a marked energy deficit in addition to intense exercise training would affect changes in body composition . DESIGN We used a single-blind , r and omized , parallel-group prospect i ve trial . During a 4-wk period , we provided hypoenergetic ( ~40 % reduction compared with requirements ) diets providing 33 ± 1 kcal/kg LBM to young men who were r and omly assigned ( n = 20/group ) to consume either a lower-protein ( 1.2 g · kg(-1 ) · d(-1 ) ) control diet ( CON ) or a higher-protein ( 2.4 g · kg(-1 ) · d(-1 ) ) diet ( PRO ) . All subjects performed resistance exercise training combined with high-intensity interval training for 6 d/wk . A 4-compartment model assessment of body composition was made pre- and postintervention . RESULTS As a result of the intervention , LBM increased ( P < 0.05 ) in the PRO group ( 1.2 ± 1.0 kg ) and to a greater extent ( P < 0.05 ) compared with the CON group ( 0.1 ± 1.0 kg ) . The PRO group had a greater loss of fat mass than did the CON group ( PRO : -4.8 ± 1.6 kg ; CON : -3.5 ± 1.4 kg ; P < 0.05 ) . All measures of exercise performance improved similarly in the PRO and CON groups as a result of the intervention with no effect of protein supplementation . Changes in serum cortisol during the intervention were associated with changes in body fat ( r = 0.39 , P = 0.01 ) and LBM ( r = -0.34 , P = 0.03 ) . CONCLUSIONS Our results showed that , during a marked energy deficit , consumption of a diet containing 2.4 g protein · kg(-1 ) · d(-1 ) was more effective than consumption of a diet containing 1.2 g protein · kg(-1 ) · d(-1 ) in promoting increases in LBM and losses of fat mass when combined with a high volume of resistance and anaerobic exercise . Changes in serum cortisol were associated with changes in body fat and LBM , but did not explain much variance in either measure . This trial was registered at clinical trials.gov as NCT01776359 Abstract Increased protein intake versus maltodextrin intake for 4 weeks lowers blood pressure . Concerns exist that high‐protein diets reduce renal function . Effects of acute and 4‐week protein intake versus maltodextrin intake on renal acid load , glomerular filtration rate and related parameters were compared in this study . Seventy‐nine overweight individuals with untreated elevated blood pressure and normal kidney function were r and omized to consume a mix of protein isolates ( 60 g/day ) or maltodextrin ( 60 g/day ) for 4 weeks in energy balance . Twenty‐four‐hour urinary potential renal acid load ( uPRAL ) was compared between groups . A subgroup ( maltodextrin N = 27 , protein mix N = 25 ) participated in extra test days investigating fasting levels and postpr and ial effects of meals supplemented with a moderate protein‐ or maltodextrin‐load on glomerular filtration rate , effective renal plasma flow , plasma renin , aldosterone , pH , and bicarbonate . uPRAL was significantly higher in the protein group after 4 weeks ( P ≤ 0.001 ) . Postpr and ial filtration fraction decreased further after the protein‐supplemented breakfast than after the maltodextrin‐supplemented breakfast after 4 weeks of supplementation ( P ≤ 0.001 ) . Fasting and postpr and ial levels of glomerular filtration rate , effective renal plasma flow , renin , aldosterone , angiotensin‐converting enzyme , pH and bicarbonate did not differ between groups . In conclusion , 4 weeks on an increased protein diet ( 25 % of energy intake ) increased renal acid load , but did not affect renal function . Postpr and ial changes , except for filtration fraction , also did not differ between groups . These data suggest that a moderate increase in protein intake by consumption of a protein mix for 4 weeks causes no ( undesirable ) effects on kidney function in overweight and obese individuals with normal kidney function Although popular and effective for weight loss , low-carbohydrate , high-protein , high-fat ( Atkins ) diets have been associated with adverse changes in blood and renal biomarkers . High-protein diets low in fat may represent an equally appealing diet plan but promote a more healthful weight loss . Healthy adults ( n = 20 ) were r and omly assigned to 1 of 2 low-fat ( < 30 % energy ) , energy-restricted groups : high-protein ( 30 % energy ) or high-carbohydrate ( 60 % energy ) ; 24-h intakes were strictly controlled during the 6-wk trial . One subject from each group did not complete the trial due to out-of-state travel ; two subjects in the high-carbohydrate group withdrew from the trial due to extreme hunger . Body composition and metabolic indices were assessed pre- and post-trial . Both diets were equally effective at reducing body weight ( -6 % , P < 0.05 ) and fat mass ( -9 to -11 % , P < 0.05 ) ; however , subjects consuming the high-protein diet reported more satisfaction and less hunger in mo 1 of the trial . Both diets significantly lowered total cholesterol ( -10 to -12 % ) , insulin ( -25 % ) , and uric acid ( -22 to -30 % ) concentrations in blood from fasting subjects . Urinary calcium excretion increased 42 % in subjects consuming the high-protein diet , mirroring the 50 % increase in dietary calcium with consumption of this diet ; thus , apparent calcium balance was not adversely affected . Creatinine clearance was not altered by diet treatments , and nitrogen balance was more positive in subjects consuming the high-protein diet vs. the high-carbohydrate diet ( 3.9 + /- 1.4 and 0.7 + /- 1.7 g N/d , respectively , P < 0.05 ) . Thus , low-fat , energy-restricted diets of varying protein content ( 15 or 30 % energy ) promoted healthful weight loss , but diet satisfaction was greater in those consuming the high-protein diet BACKGROUND Acute consumption of fat-free fluid milk after resistance exercise promotes a greater positive protein balance than does soy protein . OBJECTIVE We aim ed to determine the long-term consequences of milk or soy protein or equivalent energy consumption on training-induced lean mass accretion . DESIGN We recruited 56 healthy young men who trained 5 d/wk for 12 wk on a rotating split-body resistance exercise program in a parallel 3-group longitudinal design . Subjects were r and omly assigned to consume drinks immediately and again 1 h after exercise : fat-free milk ( Milk ; n = 18 ) ; fat-free soy protein ( Soy ; n = 19 ) that was isoenergetic , isonitrogenous , and macronutrient ratio matched to Milk ; or maltodextrin that was isoenergetic with Milk and Soy ( control group ; n = 19 ) . RESULTS Muscle fiber size , maximal strength , and body composition by dual-energy X-ray absorptiometry ( DXA ) were measured before and after training . No between-group differences were seen in strength . Type II muscle fiber area increased in all groups with training , but with greater increases in the Milk group than in both the Soy and control groups ( P < 0.05 ) . Type I muscle fiber area increased after training only in the Milk and Soy groups , with the increase in the Milk group being greater than that in the control group ( P < 0.05 ) . DXA-measured fat- and bone-free mass increased in all groups , with a greater increase in the Milk group than in both the Soy and control groups ( P < 0.05 ) . CONCLUSION We conclude that chronic postexercise consumption of milk promotes greater hypertrophy during the early stages of resistance training in novice weightlifters when compared with isoenergetic soy or carbohydrate consumption BACKGROUND The metabolic effects of diets high in vegetable protein have not been assessed despite much recent interest in the effect of soy proteins in reducing serum cholesterol . OBJECTIVE We assessed the metabolic effects of diets high in vegetable protein ( specifically , wheat gluten ) on serum lipids , uric acid concentrations , and renal function . DESIGN Twenty hyperlipidemic men and women consumed isoenergetic test ( high-protein ) and control metabolic diets for 1 mo in a r and omized crossover design . In the high-protein diet , 11 % of the total dietary energy from starch in the control bread was replaced by vegetable protein ( wheat gluten ) , result ing in 27 % of total energy from protein compared with 16 % in the control diet . In other respects , the 2 diets were identical . RESULTS Compared with the control , the high-protein diet result ed in lower serum concentrations of triacylglycerol ( by 19.2 + /- 5.6 % ; P = 0.003 ) , uric acid ( by 12.7 + /- 2.0 % ; P < 0.001 ) , and creatinine ( by 2.5 + /- 1.1 % ; P = 0.035 ) and higher serum concentrations of urea ( by 42.2 + /- 5.8 % ; P < 0.001 ) and a higher 24-h urinary urea output ( by 99.2 + /- 17.2 % ; P < 0.001 ) . No significant differences were detected in total or HDL cholesterol or in the renal clearance of creatinine . LDL oxidation , assessed as the ratio of conjugated dienes to LDL cholesterol in the LDL fraction , was lower with the high-protein diet ( by 10.6 + /- 3.6 % ; P = 0.009 ) . CONCLUSIONS High intakes of vegetable protein from gluten may have beneficial effects on cardiovascular disease risk by reducing oxidized LDL , serum triacylglycerol , and uric acid . Further studies are required to assess the longer-term effects on renal function BACKGROUND When substituted for carbohydrate in an energy-reduced diet , dietary protein enhances fat loss in women . It is unknown whether the effect is due to increased protein or reduced carbohydrate . OBJECTIVE We compared the effects of 2 isocaloric diets that differed in protein and fat content on weight loss , lipids , appetite regulation , and energy expenditure after test meals . DESIGN This was a parallel , r and omized study in which subjects received either a low-fat , high-protein ( LF-HP ) diet ( 29 + /- 1 % fat , 34 + /- 0.8 % protein ) or a high-fat , st and ard-protein ( HF-SP ) diet ( 45 + /- 0.6 % fat , 18 + /- 0.3 % protein ) during 12 wk of energy restriction ( 6 + /- 0.1 MJ/d ) and 4 wk of energy balance ( 7.4 + /- 0.3 MJ/d ) . Fifty-seven overweight and obese [ mean body mass index ( in kg/m(2 ) ) : 33.8 + /- 0.9 ] volunteers with insulin concentrations > 12 mU/L completed the study . RESULTS Weight loss ( LF-HP group , 9.7 + /- 1.1 kg ; HF-SP group , 10.2 + /- 1.4 kg ; P = 0.78 ) and fat loss were not significantly different between diet groups even though the subjects desired less to eat after the LF-HP meal ( P = 0.02 ) . The decrease in resting energy expenditure was not significantly different between diet groups ( LF-HP , -342 + /- 185 kJ/d ; HF-SP , -349 + /- 220 kJ/d ) . The decrease in the thermic effect of feeding with weight loss was smaller in the LF-HP group than in the HF-SP group ( -0.3 + /- 1.0 % compared with -3.6 + /- 0.7 % ; P = 0.014 ) . Glucose and insulin responses to test meals improved after weight loss ( P < 0.001 ) with no significant diet effect . Bone turnover , inflammation , and calcium excretion did not change significantly . CONCLUSION The magnitude of weight loss and the improvements in insulin resistance and cardiovascular disease risk factors did not differ significantly between the 2 diets , and neither diet had any detrimental effects on bone turnover or renal function Calcium balance is decreased by an increased intake of purified proteins , although the effects of common dietary sources of protein ( like meat ) on calcium economy remain controversial . We compared the effects of several weeks of controlled high and low meat diets on body calcium retention , using sensitive radiotracer and whole body scintillation counting methodology . Healthy postmenopausal women ( n = 15 ) consumed diets with similar calcium content ( approximately 600 mg ) , but either low or high in meat ( 12 Output:	Conclusions Postintervention GFR comparisons indicate that HP diets result in higher GFRs ; however , when changes in GFR were compared , dietary protein had no effect . Our analysis indicates that HP intakes do not adversely influence kidney function on GFR in healthy adults
MS21996	*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 study the effectiveness of luteinising hormone releasing hormone ( LHRH ) analogues in improving final height in girls affected by early puberty . PATIENTS Forty six consecutive girls with onset of puberty aged 7.5–8.5 years r and omly divided into two groups : one treated with 3.75 mg triptorelin intramuscularly every four weeks ( group 1 ) ; and the other with no treatment ( group 2 ) . RESULTS Mean ( SD ) chronological age at onset of menarche was significantly higher in group 1 than in group 2 ( 11.9 ( 1.0 ) v 10.8 ( 0.7 ) years ) . However , mean ( SD ) height at menarche ( 152.7 (7.2)v 152.5 ( 5.7 ) cm ) and mean ( SD ) growth after menarche ( 4.9 ( 3.0 ) v 5.4 ( 2.2 ) cm ) were similar in both groups . The mean ( SD ) final height was similar in the two groups ( group 1 , 158.1 ( 6.2 ) cm ; group 2 , 158.6 ( 6.0 ) cm ) and not significantly different from target height . Fourteen of 20 patients in group 1 and 12 of 18 patients in group 2 showed final height equal to or higher than target height . Final heights of girls with poor initial height prognosis were significantly lower than those of girls with good prognosis , but in patients with the same initial height prognosis , both groups showed final heights similar and not significantly different from their target heights . CONCLUSIONS LHRH analogue has no apparent effect on final height in subjects with onset of puberty between 7.5 and 8.5 years Early and fast puberty ( EFP ) in girls , defined as pubertal onset at age 8 - 9 yr , with an accelerated course , may cause compromised final height ( FHt ) and psychosocial distress . Treatment with a gonadotropin-suppressive agent is controversial , because the improvement in FHt is equivocal and there may be risk of obesity . We analyzed the data of 126 girls with EFP : 63 treated with GnRH analog ( GnRHA ) since Tanner stage 3 , for 2 - 4 yr ; and 63 untreated . Age at onset of puberty ; accelerated time of transition from Tanner stage 2 to 3 ( < 1.3 yr ) ; and clinical , hormonal and sonographic findings were similar in the 2 groups . The girls given GnRHA treatment had a significantly prolonged pubertal course , compared with the accelerated course in the untreated girls ( 4.7 + /- 0.4 vs. 2.45 + /- 0.4 yr , P < 0.001 ) . After therapy , they reached Tanner stages 4 and 5 and FHt at a significantly older age than the untreated group ( P < 0.001 ) , and their menarche was delayed ( 12.8 + /- 0.6 vs. 10.8 + /- 0.5 yr , P < 0.001 ) . However , the different pace of puberty in the 2 groups did not change the total pubertal growth and the bone maturation rate . The Ht gain from Tanner stage 3 to 4 ( 10.4 + /- 2.7 vs. 11.2 + /- 3.1 cm ) and from Tanner stage 4 to FHt ( 8.2 + /- 2.7 vs. 8.8 + /- 3.6 cm ) was similar in the treated and untreated girls , as were absolute Ht and bone age at each pubertal stage . The weight gain of the treated girls was more pronounced during treatment ( P = 0.0016 ) , but it was arrested after discontinuation of therapy ; and by the time FHt was reached , the body mass index was similar in the 2 groups . The treated and untreated girls achieved a similar mean FHt , which was not significantly different from their respective mean target Ht ( THt ) . Individual analysis revealed that 70 % of the treated girls and 67 % of the untreated girls attained their THt range ( THt + /- 0.5 SD ) or surpassed it . In conclusion , treatment with GnRHA affected only the pace of EFP . The similar Ht gain and bone maturation rate at each pubertal stage in the treated and untreated girls may suggest that the total pubertal growth is not dependent on pubertal duration and pace and is probably determined already at the onset of the normal pubertal development . The treatment did not compromise the FHt and did not cause long-lasting obesity . Therefore , GnRHA therapy may be suggested for use in girls who have psychosocial difficulties in coping with EFP Twenty-two girls affected by sexual precocity with impaired final height prognosis were followed until they achieved final height . Twelve of them were treated with an intranasal (D-Ser6)-gonadotrophin-releasing hormone ( GnRH ) analogue ( buserelin ) administered at a mean dose of 25 micrograms/kg/day ( range 20 - 32 ) for a mean period of 14 months ( range 8 - 18 ) . Ten girls refused treatment . Mean final height of the treated girls was 157.3 + /- 8.2 cm , significantly ( p = 0.03 ) higher than the 149.7 + /- 5.5 cm of untreated patients . Treated girls surpassed midparental height ( + 1.7 cm ) while untreated girls reached the lower part of target zone ( -3.5 cm ) . Our data suggest that intranasal buserelin treatment preserves final height in girls with sexual precocity and initially impaired height prognosis Objective : To investigate the effects of treatment with gonadotropin-releasing hormone analog ( GnRHa ) on final height in girls who experienced moderately early puberty with symptoms beginning at 7 - 8.5 years of age . Methods : Female cases diagnosed with moderately early puberty which had started between ages 7 to 8.5 years were included in the study . In the treatment groups , all cases with a bone age ≤10.5 years constituted group 1 ( n=18 ) and those with a bone age > 10.5 years constituted group 2 ( n=23 ) . The 8 patients for which treatment approval could not be obtained constituted group 3 . The 49 cases in all three groups were observed until they reached their final height . Results : Target height , target height st and ard deviation score ( SDS ) , final height , and final height SDS values were similar in all 3 groups . Final height showed a significant positive correlation with target height ( p=0.000 , r=0.54 ) and height at diagnosis ( p=0.003 , r=0.467 ) in all groups . Linear regression analysis revealed that a 1 cm longer height at diagnosis increased the final height 0.213 fold , and a 1 cm longer target height at diagnosis increased the final height 0.459 fold . Conclusion : We found that GnRHa did not make a positive contribution to final height in cases of moderately early puberty BACKGROUND We analysed the effectiveness of therapy with LHRH analogues in girls with a puberty onset at age 8 years . PATIENTS AND METHOD We performed a non-r and omised clinical study of 32 girls with advanced puberty . These included 16 treated with triptorelin LHRH analogue(3.75 mg/month during 1 year ) and 16 control subjects . We carried out anthropometric measurements and determined the pubertal height growth ( gain in height from the puberty onset up to the final height ) and the pubertal duration ( time in years from the puberty onset up to the age at which final height is attained ) . RESULTS Treatment with LHRH analogue delayed the menarche age ( 11.5 [1.46]vs 10.37 [ 0.67 ] years of age ; p = 0.03 ) , led to an involution in secondary sexual characteristics and a temporary decrease ingrowth rate , and delayed skeletal maturation . However , pubertal duration , pubertal height growth and final height were all similar in both groups . In addition , no significant differences in body fat mass were observed . CONCLUSIONS Treatment with LHRH analogues in advanced puberty modifies pubertal development , without modifying pubertal duration or pubertal height growth . Furthermore , this treatment does not improve final height Puberty is a period characterized by growth spurt and rapid change in body composition . The effect of GnRH agonist therapy for central precocious puberty on bone mineral density is unclear . We demonstrated changes in bone mineral density in subjects with central precocious puberty , who were treated with GnRH agonist for more than 3 years OBJECTIVE To evaluate prospect ively pubertal and predicted adult height progression until final height ( FH ) or near FH in girls with apparent idiopathic precocious puberty who were not treated . STUDY DESIGN The decision not to treat at the time of initial evaluation was based on evidence of slowly progressive puberty as shown by bone age ( BA ) advancement < 2 years above the chronologic age , whatever the hypothalamic pituitary ovarian axis activation , or no evidence of hypothalamic pituitary ovarian axis activation , whatever the BA advancement . During follow-up , patients who showed a significant decrease in predicted FH were treated with gonadotropin-releasing hormone agonist . RESULTS Twenty-six girls with idiopathic precocious puberty were studied at a mean chronologic age of 7.4 + /- 0.9 years during a follow-up period of 6.6 + /- 2.2 years until FH or near FH . During the first 2 years of follow-up , most of the patients ( group 1 , n = 17 ; 65 % of the cases ) showed no substantial changes in predicted FH . They never required treatment , and menarche occurred at a mean chronologic age of 11.9 + /- 0.6 years . Their mean FH ( or near FH ) at 160.7 + /- 5.7 cm was close to their target height ( 161.3 + /- 4.7 cm ) . On the other h and , after a mean follow-up period of 1.4 + /- 0.8 years , 9 patients ( group 2 ) had acceleration of bone maturation and deterioration of their predicted FH ( from 162.1 + /- 6 . 2 cm to 155.3 + /- 5.6 cm ; P < .01 ) , which was at that time significantly lower than their target height ( P < .05 ) ( mean target height = 159.8 + /- 4.6 cm ) . They received a gonadotropin-releasing hormone agonist for 2.1 + /- 0.7 years , result ing in a restoration of growth prognosis ( mean FH or near FH = 160.2 + /- 6.7 cm ) . CONCLUSIONS This study demonstrates that not all patients with apparent idiopathic precocious puberty require medical treatment , notably when there is no evidence of hypothalamo-pituitary ovarian activation or no significantly advanced BA to impair height potential . Most show a slowly progressing puberty . However , careful follow-up of these patients is necessary up to at least 9 years of age , because until then height prediction may deteriorate , necessitating gonadotropin-releasing hormone agonist treatment in one third of the cases BACKGROUND To evaluate the effect of GnRH-analogue triptoreline on the predicted adult height and final height in central precocious puberty ( CPP ) . PATIENTS AND METHODS The study included 14 girls with CPP treated for 1 - 6 years with triptoreline depot ( 75 micrograms/kg/28 days/i.m . ; group 1 ) . The criteria for diagnosis included the following : compelling evidence of rapid progression of puberty , with a bone age ( BA ) greater than 2 SD above the mean value for chronological age ( CA ) associated with poor initial predicted final height and growth speed greater than 2 SD above the mean value for age . In addition we obtained data from 6 untreated girls with advanced puberty and good predicted adult height followed during the same period of time ( group II ) . 7 of 14 girls of group I and 5 of 6 girls of group II attained final height . RESULTS A decrease in growth speed and an increase and in CA/BA ratio were observed after three years of treatment ( + 4.9 + /- 0.7 SD to -1.45 + /- 2.63 SD and 0.62 + /- 0.14 to 0.74 + /- 0.09 respectively ; P = 0.034 ; n = 6 ) . The predicted adult height increased significantly after two years of treatment ( 153.1 + /- 4.49 to 156.94 + /- 5 cm ; p = 0.041 ; n = 10 ) and was more evident after three years of treatment ( 153.84 + /- 5.77 to 160.7 + /- 7.5 cm ; p = 0.03 ; n = 6 ) . The final height of 7 girls of group I who attained it was similar to target height ( 161 + /- 3.1 vs. 159 + /- 1.3 cm ; NS ) and greater than initial predicted adult height ( 161 + /- 3.1 vs. 154 + /- 2.1 cm ; p = 0.044 ) and than final height of the 5 girls of group II ( 161 + /- 3.1 vs. 154.28 + /- 6.1 cm ) . CONCLUSIONS Triptorelin dep Output:	Conclusion We found no evidence from controlled experimental and observational studies that compared with no treatment , the use of GnRH analogs improved AH in girls with EP
MS21997	*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 : Disease management programmes ( DMPs ) improve quality of care for patients with heart failure ( HF ) . However , only a limited number of trials have studied the efficacy of such programmes for patients with heart failure with preserved ejection fraction ( HFPEF ) . Objective : To estimate the impact of a structured , nurse-led patient education programme and care plan in general practice on outcome parameters and events in patients with HFPEF . Methods : Single blinded r and omized clinical trial with an intervention over six months and a follow-up during 12 additional months . In the control group , the patients ( n = 41 ) were managed according to Russian national guidelines . Patients in the intervention group ( n = 44 ) received education on individual lifestyle changes and modifications of cardiovascular disease ( CVD ) risk factors , home-based exercise training and weekly nurse consultations in addition to usual care . Results : Six months after their inclusion , patients in the intervention group significantly improved body mass index , waist circumference , six-min walk test distance , total cholesterol , low-density lipoprotein , left ventricular end-diastolic volume index , quality of life and level of anxiety . After 18 months , there were 11 deaths ( 25 % ) or hospitalizations in the intervention group and 12 ( 29 % ) in the control group ( P = 0.134 ) . Cardiovascular mortality and readmission rate were not reduced significantly after six months of follow-up : the hazard ratio was 0.47 ( 95 % CI : 0.17–1.28 ; P = 0.197 ) . After 18 months , this was 0.85 ( 0.42–1.73 ; P = 0.658 ) . Conclusion : This primary care based DMP for patients with HFPEF improved the patients ’ emotional status and quality of life , positively influenced body weight , functional capacity and lipid profile , and attenuated heart remodelling BACKGROUND Preliminary evidence suggests that meditative exercise may have benefits for patients with chronic systolic heart failure ( HF ) ; this has not been rigorously tested in a large clinical sample . We sought to investigate whether tai chi , as an adjunct to st and ard care , improves functional capacity and quality of life in patients with HF . METHODS A single-blind , multisite , parallel-group , r and omized controlled trial evaluated 100 out patients with systolic HF ( New York Heart Association class I-III , left ventricular ejection fraction ≤40 % ) who were recruited between May 1 , 2005 , and September 30 , 2008 . A group-based 12-week tai chi exercise program ( n = 50 ) or time-matched education ( n = 50 , control group ) was conducted . Outcome measures included exercise capacity ( 6- minute walk test and peak oxygen uptake ) and disease-specific quality of life ( Minnesota Living With Heart Failure Question naire ) . RESULTS Mean ( SD ) age of patients was 67 ( 11 ) years ; baseline values were left ventricular ejection fraction , 29 % ( 8 % ) and peak oxygen uptake , 13.5 mL/kg/min ; the median New York Heart Association class of HF was class II . At completion of the study , there were no significant differences in change in 6-minute walk distance and peak oxygen uptake ( median change [ first quartile , third quartile ] , 35 [ -2 , 51 ] vs 2 [ -7 , 54 ] meters , P = .95 ; and 1.1 [ -1.1 , 1.5 ] vs -0.5 [ -1.2 , 1.8 ] mL/kg/min , P = .81 ) when comparing tai chi and control groups ; however , patients in the tai chi group had greater improvements in quality of life ( Minnesota Living With Heart Failure Question naire , -19 [ -23 , -3 ] vs 1 [ -16 , 3 ] , P = .02 ) . Improvements with tai chi were also seen in exercise self-efficacy ( Cardiac Exercise Self-efficacy Instrument , 0.1 [ 0.1 , 0.6 ] vs -0.3 [ -0.5 , 0.2 ] , P < .001 ) and mood ( Profile of Mood States total mood disturbance , -6 [ -17 , 1 ] vs -1 [ -13 , 10 ] , P = .01 ) . CONCLUSION Tai chi exercise may improve quality of life , mood , and exercise self-efficacy in patients with HF . Trial Registration clinical trials.gov Identifier : NCT00110227 Heart failure ( HF ) is the leading cause of rehospitalization in older adults . The purpose of this pilot study was to examine whether telemonitoring by an advanced practice nurse reduced subsequent hospital readmissions , emergency department visits , costs , and risk of hospital readmission for patients with HF . One hundred two patient/caregiver dyads were r and omized into 2 groups postdischarge ; 84 dyads completed the study . Hospital readmissions , emergency department visits , costs , and days to readmission were abstract ed from medical records . Participants were interviewed soon after discharge and 3 months later about effects of telemonitoring on depressive symptoms , quality of life , and caregiver mastery . There were no significant differences due to telemonitoring for any outcomes . Caregiver mastery , informal social support , and electronic home monitoring were not significant predictors for risk of hospital readmission . Further studies should address the interaction between the advanced practice nurse and follow-up intervention with telemonitoring of patients with HF to better target those who are most likely to benefit AIMS Supervised exercise can benefit selected patients with heart failure , however the effectiveness of home-based exercise remains uncertain . We aim ed to assess the effectiveness of a home-based exercise programme in addition to specialist heart failure nurse care . METHODS AND RESULTS This was a r and omized controlled trial of a home-based walking and resistance exercise programme plus specialist nurse care ( n=84 ) compared with specialist nurse care alone ( n=85 ) in a heart failure population in the West Midl and s , UK . PRIMARY OUTCOME Minnesota Living with Heart Failure Question naire ( MLwHFQ ) at 6 and 12 months . SECONDARY OUTCOMES composite of death , hospital admission with heart failure or myocardial infa rct ion ; psychological well-being ; generic quality of life ( EQ-5D ) ; exercise capacity . There was no statistically significant difference between groups in the MLwHFQ at 6 month ( mean , 95 % CI ) ( -2.53 , -7.87 to 2.80 ) and 12 month ( -0.55 , -5.87 to 4.76 ) follow-up or secondary outcomes with the exception of a higher EQ-5D score ( 0.11 , 0.04 to 0.18 ) at 6 months and lower Hospital Anxiety and Depression Scale score ( -1.07 , -2.00 to -0.14 ) at 12 months , in favour of the exercise group . At 6 months , the control group showed deterioration in physical activity , exercise capacity , and generic quality of life . CONCLUSION Home-based exercise training programmes may not be appropriate for community-based heart failure patients AIM One of the major treatment goals in congestive heart failure ( CHF ) is to preserve the functional level of the patient and to improve psychosocial factors . For these purpose s , exercise training is recommended for the management of CHF . With this background , the aim of this study is to investigate the effects of aerobic exercise on quality of life , depression and anxiety levels in a Turkish patient population with CHF . METHODS Sixty patients with CHF in stage II-III according to NYHA were included . Patients were r and omly assigned either to a cardiac rehabilitation group or to a control group . Twenty-seven patients were allocated to a weekly aerobic walking program on treadmill , thrice a week for 8 weeks , and 26 patients did not receive any exercise training . Both groups were assessed by an ergospirometric exercise test , Hacettepe Quality of Life Question naire ( HQoL ) , Beck Depression Inventory ( BDI ) , Spielberger Trait Anxiety Inventory ( STAI ) at baseline and at the end . RESULTS Forty-four patients ( treatment group : 23 ) completed the study . In the treatment group , significant increases in peak oxygen consumption , exercise time and metabolic equivalents ( MET ) levels were attained ( P=0.001 , P=0.001 , P=0.003 , respectively ) . Significant decreases in BDI ( P=0.004 ) and STAI subgroups ( P=0.049 , P=0.023 , respectively ) were observed , whereas there was no change in HQoL scores . In the control group , there was no difference between baseline and 8th week evaluation in all parameters . CONCLUSIONS Patients with CHF tolerated aerobic exercise programs well . This result ed with improvement in both physical and psychologic wellbeing , but not in quality of life in the short term The purpose of this study was to evaluate the effect of stress management training on quality of life , functional capacity , and heart rate variability in elderly patients with New York Heart Association class I-III congestive heart failure ( CHF ) . While substantial research exists on stress management training for patients with coronary heart disease , there are few data on the value of psychosocial training on patients with CHF . Thirty-three multiethnic patients ( mean age , 66+/-9 years ) were assigned through incomplete r and omization to one of two treatment groups or a wait-listed control group . The 14 participants who completed the treatment attended eight training sessions during a 10-week period . The training consisted of 75-minute sessions adapted from the Freeze-Frame stress management program developed by the Institute of HeartMath . Subjects were assessed at baseline and again at the completion of the training . Depression , stress management , optimism , anxiety , emotional distress , and functional capacity were evaluated , as well as heart rate variability . Significant improvements ( p<0.05 ) were noted in perceived stress , emotional distress , 6-minute walk , and depression , and positive trends were noted in each of the other psychosocial measures . The 24-hour heart rate variability showed no significant changes in autonomic tone . The authors noted that CHF patients were willing study participants and their emotional coping and functional capacity were enhanced . This program offers a simple and cost-effective way to augment medical management of CHF . Given the incompleteness of CHF medical management and the exploding interest in complementary medical intervention , it seems imperative that further work in psychosocial treatment be undertaken Objectives : To evaluate the feasibility of screening and recruiting patients with major depression and congestive heart failure ( CHF ) in a tertiary care cardiology hospital and to obtain preliminary efficacy , tolerability , and safety data for nefazodone treatment of a major depressive episode in CHF patients . Method : We conducted a 12-week , open-label trial of nefazodone given in dosages up to 600 mg daily . We assessed patients at baseline , 1 , 2 , 4 , 8 , and 12 weeks . Measures used were the 17-item Hamilton Depression Rating Scale ( HDRS ) , the Clinical Global Impression Scale , the Beck Depression Inventory , Spielberger 's State-Trait Anxiety Inventory , and the Minnesota Living with Heart Failure Question naire . We also obtained pre- and post study ECGs , 24-hour Holter monitor recordings , and plasma levels of norepinephrine . Results : After screening 443 CHF patients , 28 patients with major depression met study eligibility criteria . The 23 patients who completed 4 or more weeks of medication showed significant improvement on all depression scales and in quality of life . Of 19 subjects who completed the full 12-week trial , 74 % experienced a decline of 50 % or more on HDRS scores . The completers also showed a significant reduction in heart rate , an increase in QT intervals ( but not in the QTc ) , and a marginally significant decrease in plasma norepinephrine . There were no changes in heart rate variability . Conclusions : It is feasible to screen and recruit CHF patients with major depression for an antidepressant trial . Nefazodone seems sufficiently safe , tolerable , and efficacious to justify a larger , placebo-controlled trial Purpose To compare the effects of home-based and hospital-based exercise programs on exercise capacity , quality of life , psychological symptoms , and hemodynamic parameters in heart failure ( HF ) patients . Methods Seventy-four patients were r and omized into either a hospital-based exercise ( Group 1 ) or a home-based exercise ( Group 2 ) group . Prior to and after the 8-week rehabilitation program , the two groups were compared with respect to their functional capacity [ maximal oxygen uptake ( pVO2 ) and 6-min walk test ( 6MWT ) ] , quality of life ( Medical Outcomes Study and the 36-item Short Form Survey , SF-36 ) , psychological symptoms [ Beck Depression Inventory ( BDI ) and State-Trait Anxiety Inventory ] , and hemodynamic parameters [ ( left ventricular diastolic diameter in diastole , left ventricular diameter in systole , Mitral Early diastolic peak flow velocity (E)/late diastolic peak flow velocity ( A ) , Mitral E/Mitral early peak velocity ( Em ) , Tei index , right ventricular systolic peak velocity ( Sm ) , tricuspid annular plane systolic excursion , systolic pulmonary arterial pressure ( SPAP ) , and left and right ventricular ejection fraction ( LVEF and RVEF ) ] . Results After the exercise programs , significant improvement was observed in pVO2 , 6MWT and subscales of physical function , general health , and vitality of SF 36 , as well as BDI and LVEF in both groups ( P < 0.05 ) . A comparison of the two exercise groups revealed no significant differences between them regarding the analyzed variables ( P > 0.05 ) . Conclusion Both the hospital-based and home- Output:	Studies with SSRIs examined effects of sertraline , paroxetine , and citalopram . CONCLUSIONS Evidence is strong that pharmacology and CAM may improve depression . Moderate evidence supports the use of exercise . A strong body of evidence indicates that disease management programs do not improve depression .
MS21998	*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: Outcomes of seven treatment trials comparing cognitive behavioral therapy to treatment with tricyclic antidepressant medication in major depressive disorder have been quite similar to one another . This led us to question whether treatment outcome in time-limited studies reflected a unique effect of cognitive behavioral therapy . To test the uniqueness hypothesis , relaxation training , a nonpharmacologic , noncognitive treatment , was chosen as a comparison for cognitive behavioral therapy as well as drug therapy . Treatment duration was 16 weeks . The sample of 37 patients treated for major depressive disorder was less depressed than those previously studied . For both cognitive behavioral therapy and relaxation training , outcome of depression was superior to that of tricyclic antidepressant medication by endpoint analysis . The posttreatment scores on the Beck Depression Inventory of 82 % of the group receiving cognitive behavioral therapy improved to a Beck Depression Inventory score ≤9 which was not significantly greater than that for the group receiving relaxation training.(73 % ) , so a unique effect was not demonstrated for cognitive behavioral therapy . The outcome for tricyclic antidepressant medication ( 29 % improved to criteria ) was significantly worse than that for cognitive behavioral therapy . The patient 's pretreatment initial expectancy was not predictive Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed BACKGROUND Psychotherapy 's equivalence paradox is that treatments tend to have equivalently positive outcomes despite non-equivalent theories and techniques . We replicated an earlier comparison of treatment approaches in a sample four times larger and restricted to primary -care mental health . METHOD Patients ( n=5613 ) who received cognitive-behavioural therapy ( CBT ) , person-centred therapy ( PCT ) or psychodynamic therapy ( PDT ) at one of 32 NHS primary -care services during a 3-year period ( 2002 - 2005 ) completed the Clinical Outcomes in Routine Evaluation - Outcome Measure ( CORE-OM ) at the beginning and end of treatment . Therapists indicated which approaches were used on an End of Therapy form . We compared outcomes of groups treated with CBT ( n=1045 ) , PCT ( n=1709 ) , or PDT ( n=261 ) only or with one of these plus one additional approach ( e.g. integrative , supportive , art ) , design ated CBT+1 ( n=1035 ) , PCT+1 ( n=1033 ) , or PDT+1 ( n=530 ) , respectively . RESULTS All six groups began treatment with equivalent CORE-OM scores , and all averaged marked improvement ( overall pre/post effect size=1.39 ) . Neither treatment approach nor degree of purity ( ' only ' v. ' + 1 ' ) had a statistically significant effect . Distributions of change scores were all similar . CONCLUSIONS Replicating the earlier results , the theoretically different approaches tended to have equivalent outcomes . Caution is warranted because of limited treatment specification , non-r and om assignment , incomplete data , and other issues . Insofar as these routine treatments appear effective for patients who complete them , those who fail to complete ( or to begin ) treatment deserve attention by research ers and policymakers In a study design ed to maximize the effectiveness of treatment by allowing participants to select the target of treatment , 40 depressed older adults were r and omly assigned to a waiting-list control condition or to conditions in which the target of treatment was either chosen or assigned . All participants received self-management therapy and the choice was between changing behavior or changing cognition . It was found that individually administered self-management therapy was effective in treating depression for older adults . There were no differences in outcome between versions of self-management therapy that targeted behavioral or cognitive change . Among those who completed treatment , there were no differences in outcome between those who received a choice and those who did not . Individuals who were given a choice of treatment options , however , were less likely to drop out of treatment prematurely BACKGROUND cognitive impairment is an important part of the diagnostic criteria for dementia . The Mini-Mental State Examination ( MMSE ) is recommended to test for cognitive impairment and to monitor medication response . OBJECTIVES we examined the prevalence of cognitive impairment in the UK and assessed associations with cognitive impairment . DESIGN cross-sectional survey as part of a cluster r and omised trial . SUBJECTS representative sample of people aged 75 years and over . METHODS all subjects had a detailed baseline health assessment including the MMSE . RESULTS a total of 15,051 subjects completed the assessment ( 71.9 % ) . Almost two-thirds of subjects were female ( 61.5 % ) and almost half were aged between 75 and 79 years ( 47.0 % ) . The prevalence of cognitive impairment was 18.3 % ( 95 % confidence intervals ( CI ) = 16.0 - 20.9 ) at a cut-off of 23/24 , and 3.3 % ( 95 % CI = 2.8 - 4.0 ) at 17/18 . Those with impairment ( MMSE 23/24 ) were significantly more likely to have hearing ( odds ratio ( OR ) 1.7 ) , vision ( OR 1.7 ) and urinary incontinence problems ( OR 1.3 ) , have two or more falls in the previous 6 months ( OR 1.4 ) , and report poorer health ( OR 1.9 ) . Almost half the participants lived alone ( n = 7,073 ; 47.0 % ) and of these almost one-fifth were impaired ( MMSE 23/24 ; 19.4 % ) . CONCLUSIONS there was a high prevalence of cognitive impairment . This representative sample demonstrates the potential burden of disease and service dem and s. It supports the need for a broader assessment of functioning as recommended by the National Service Framework for Older People , particularly in people with cognitive impairment OBJECTIVE Different studies show the negative effects on caregivers ' health of maladaptive thoughts and the positive effects of engaging in pleasurable activities on distress . The aim of this study is to ( a ) test the efficacy of a cognitive-behavioral intervention aim ed at training caregivers to flexibilize maladaptive thoughts regarding caregiving and increasing their leisure activities and to ( b ) analyse the mediator role in the effects of the intervention of caregivers ' change in dysfunctional thoughts and behavioral activation . METHODS A total of 170 caregivers were contacted and r and omly distributed to the intervention condition or to the control group . Depression , behavioral activation , and dysfunctional thoughts were assessed at baseline and post-intervention by ' blinded ' interviewers . The intervention consisted in twelve group based sessions in which in addition to cognitive-behavioral techniques , caregivers ' were trained in basic principles for caring for a relative with dementia . RESULTS Significant intervention by time effects were found for depression , dysfunctional thoughts and frequency of leisure activities . Only significant positive effects were found for the intervention group . The regression analysis for testing mediational effects of dysfunctional thoughts and leisure activities on the relationship between participating on the intervention and changes in depressive symptomatology show that mediation is established in both cases . CONCLUSIONS The results of our study contribute to the literature on interventions for dementia caregivers highlighting the positive mediator effect that modifying caregivers ' dysfunctional thoughts and increasing their behavioral activation has on caregivers ' depressive symptomatology Older adults who met criteria for major depressive disorder were r and omly assigned to behavioral , cognitive , or brief dynamic therapy . Symptoms were equally reduced across the three treatment conditions . Early in treatment , alliance ratings were obtained from both therapists and patients and were related to outcome . We calculated one therapist alliance composite score and five patient alliance factor scores . In general , no agreement was found between therapists ' and patients ' judgments of alliance . Levels of alliance were found to be not significantly different across the three treatment conditions . For the sample as a whole , only the patient factor of Patient Commitment was found to be associated with depressive symptoms after treatment , with the strongest findings in the cognitive therapy condition . The Patient Commitment factor uniquely contributed to outcome over and above the contribution of initial symptomatology and symptomatic change at midpoint in therapy . Expected trends of association with outcome were observed for the therapist alliance composite score in brief dynamic therapy and for the patient factor of Patient Working Capacity in both cognitive and brief dynamic therapy . Findings are discussed in terms of their theoretical and clinical implication OBJECTIVES To describe the patterns of self-reported medication use , including both prescription and non-prescription drugs , for older people in five areas in Engl and and Wales , and to identify the effects of socio-demographic features on medication use . DESIGN A cross-sectional survey on population r and om sample s of people aged 65 and over . The survey is a part of the screening interviews at the first stage of the Medical Research Council Cognitive Function and Ageing Study ( MRC CFAS ) carried out between 1991 and 1994 . The sample was stratified to provide equal numbers in the 65 - 74 years and 75 years and over age groups . SETTING Three urban ( Newcastle , Nottingham and Oxford ) and two rural ( Cambridgeshire and Gwynedd ) centres . Older people living in both the general community and institutions were included . PARTICIPANTS 12489 older people whose medication data were collected among the 13009 participants of the CFAS , of which the participation rate is 80 % . RESULTS Overall prevalence of medication use was 75 % ( 95 % confidence interval 74 - 76 % ) for people aged 65 - 74 and 84 % ( 83 - 85 % ) for people aged 75 and over , with a mean number of 2.03 ( st and ard deviation 1.95 ) and 2.47 ( 2.02 ) drugs reported per respondent in each group , respectively . Concurrent use of five or more drugs ( polypharmacy ) was found in 11 % ( 10 - 12 % ) of people in the 65 - 74 age group and in 15 % ( 14 - 16 % ) in the 75 and over age group . People aged 75 and over were more likely to be taking at least one drug than people aged 65 - 74 ( OR=1.69 , 1.54 - 1.85 ) , and women were more likely to be so compared with men ( OR=1.43 , 1.30 - 1.56 ) . Centre variation was found but none of the centres consistently showed higher or lower usage of medications across the major drug categories . People living in institutions were more likely to be taking gastrointestinal drugs , central nervous system drugs and experience polypharmacy . The use of respiratory and central nervous system drugs ( except hypnotics and anxiolytics ) increased in lower social class and decreased in people attending full-time education for 10 years or more . The use of haematology/dietetic drugs ( 85 % of which were vitamin and mineral preparations ) decreased in lower social class . CONCLUSION This study provides representative estimates of medication usage among older people in Engl and and Wales and identified associated factors and regional variations for medication use in a category-specific manner . The findings , suggesting the existence of centre variation and the association between type of accommodation , social class and medication use warrant further investigation Cross-sectional and longitudinal data are presented from a 2-year follow-up study of 91 older adults , initially diagnosed as in an episode of major depressive disorder ( MDD ) , who were treated with brief cognitive , behavioral , or psychodynamic psychotherapy . Using research diagnostic criteria ( RDC ) , 52 % , 58 % , and 70 % of the sample did not meet criteria for any RDC depressive disorder at posttherapy , and 12- and 24-month follow-ups , respectively . There were no significant differences in response rate by therapy modality . Using Longitudinal Interval Follow-up Evaluation ( LIFE ; Shapiro & Keller , 1979 ; Keller et al. , 1987 ) methodology , we noted that patients not depressed at posttreatment remained depression-free for longer time periods than those who were minor or MDD . These rates compare favorably with published reports on younger depressed patients OBJECTIVE Clinical guidelines recommend that antidepressant treatment should be continued for a minimum of 6 months following response in depression and anxiety disorders . However , adherence to antidepressants is low . This prospect i ve cohort study investigated the influence of patients ' antidepressant concerns , treatment preferences , and illness perceptions on adherence to antidepressants over a 6-month period . METHOD A cohort of 178 patients aged 18 to 74 years and newly issued with a prescription for antidepressants to treat any condition was followed up prospect ively at 5 primary care practice s in Southeast Engl and . Output:	AUTHORS ' CONCLUSIONS We found low- to moderate- quality evidence that behavioural therapies and other psychological therapies are equally effective .
MS21999	*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 There are no controlled , prospect i ve studies comparing the 10-year outcomes of anterior cruciate ligament ( ACL ) reconstruction using patellar tendon ( PT ) and 4-str and hamstring tendon ( HT ) autografts . HYPOTHESIS Comparable results are possible with HT and PT autografts . STUDY DESIGN Cohort study ; Level of evidence , 2 . METHODS One hundred eighty ACL-deficient knees that met inclusion criteria underwent ACL reconstruction ( 90 HT autograft , 90 PT autograft ) by one surgeon and were treated with an accelerated rehabilitation program . All knees were observed in a prospect i ve fashion with subjective , objective , and radiographic evaluation at 2 , 5 , 7 , and 10-year intervals . RESULTS At 10 years , there were no differences in graft rupture rates ( 7/90 PT vs. 12/90 HT , P = .24 ) . There were 20 contralateral ACL ruptures in the PT group , compared with 9 in the HT group ( P = .02 ) . In all patients , graft rupture was associated with instrumented laxity > 2 mm at 2 years ( P = .001 ) . Normal or near-normal function of the knee was reported in 97 % of patients in both groups . In the PT group , harvest-site symptoms ( P = .001 ) and kneeling pain ( P = .01 ) were more common than in the HT group . More patients reported pain with strenuous activities in PT knees than in HT knees ( P = .05 ) . Radiographic osteoarthritis was more common in PT knees than the HT-reconstructed knees ( P = .04 ) . The difference , however , was composed of patients with mild osteoarthritis . Other predictors of radiographic osteoarthritis were < 90 % single-legged hop test at 1 year and the need for further knee surgery . An " ideal " outcome , defined as an overall International Knee Documentation Committee grade of A or B and a radiographic grade of A at 10 years after ACL reconstruction , was associated with <3 mm of instrumented laxity at 2 years , the absence of additional surgery in the knee , and HT grafts . CONCLUSIONS It is possible to obtain excellent results with both HT and PT autografts . We recommend HT reconstructions to our patients because of decreased harvest-site symptoms and radiographic osteoarthritis Background : Recent literature has demonstrated that involvement in pivoting sports at the time of injury , increased posterior-inferior tibial slope ( PITS ) , anterolateral capsular ligament ( ALCL ) disruptions , and combined lateral meniscal lesions all contribute to a higher grade of pivot shift after acute anterior cruciate ligament ( ACL ) injuries . Purpose : To identify risk factors associated with grade 3 pivot shift after acute ACL injuries . Study Design : Case-control study ; Level of evidence , 3 . Methods : A data base of patients undergoing primary ACL reconstruction from 2009 to 2015 after acute ACL injuries was retrospectively review ed . A total of 30 patients ( 30 knees ) with grade 3 pivot shift were identified as the study group . Moreover , 30 patients ( 30 knees ) with grade 1 and 30 patients ( 30 knees ) with grade 2 pivot shift were r and omly chosen as the 2 control groups . All pivot-shift tests were performed with the patients under anesthesia . Predictors of grade 3 pivot shift that were explored included patient age , sex , time from injury to surgery , pivoting sports involvement at the time of injury , lateral PITS , medial PITS , ALCL disruptions , preoperative KT-1000 arthrometer side-to-side difference , and combined lateral or medial meniscal lesions . Comparisons were performed between the study group and the 2 control groups . Univariable and multivariable logistic regressions were used to identify independent risk factors that were associated with grade 3 pivot shift . Results : Univariable and multivariable logistic regressions between the study group and the 2 control groups showed that pivoting sports involvement at the time of injury ( odds ratio1 [ OR1 ; grade 3 vs grade 1 pivot shift with grade 1 = reference ] , 11.88 ; 95 % CI , 1.94 - 149.91 ; OR2 [ grade 3 vs grade 2 pivot shift with grade 2 = reference ] , 3.41 ; 95 % CI , 1.92 - 22.60 ) , abnormal degree of lateral PITS ( OR1 , 14.41 ; 95 % CI , 1.69 - 174.78 ; OR2 , 6.41 ; 95 % CI , 1.48 - 47.70 ) , ALCL disruptions ( OR1 , 8.28 ; 95 % CI , 1.71 - 117.14 ; OR2 , 4.96 ; 95 % CI , 1.07 - 28.75 ) , and combined lateral meniscal lesions ( OR1 , 27.56 ; 95 % CI , 5.48 - 240.52 ; OR2 , 5.83 ; 95 % CI , 1.21 - 38.56 ) were independent risk factors of grade 3 pivot shift after acute ACL injuries . Conclusion : For acute ACL injuries , the best set of predictors of grade 3 pivot shift were pivoting sports involvement at the time of injury , abnormal lateral PITS , ALCL disruptions , and combined lateral meniscal lesions . These results may provide additional information for counseling patients on residual laxity and risks for graft rerupture after ACL reconstruction Background The risk of tear of the intact anterior cruciate ligament in the contralateral knee after anterior cruciate ligament reconstruction of the opposite knee and the incidence of rupturing the anterior cruciate ligament graft during the first 2 years after surgery have not been extensively studied in a prospect i ve manner . Clinicians have hypothesized that the opposite normal knee is at equal or increased risk compared with the risk of anterior cruciate ligament graft rupture in the operated knee . Hypothesis The risk of anterior cruciate ligament graft rupture and contralateral normal knee anterior cruciate ligament rupture at 2-year follow-up is equal . Study Design Cohort study ; Level of evidence , 2 . Methods The Multicenter Orthopaedic Outcome Network ( MOON ) data base of a prospect i ve longitudinal cohort of anterior cruciate ligament reconstructions was used to determine the number of anterior cruciate ligament graft ruptures and tears of the intact anterior cruciate ligament in the contralateral knee at 2-year follow-up . Two-year follow-up consisted of a phone interview and review of operative reports . Results Two-year data were obtained for 235 of 273 patients ( 86 % ) . There were 14 ligament disruptions . Of these , 7 were tears of the intact anterior cruciate ligament in the contralateral knee ( 3.0 % ) and 7 were anterior cruciate ligament graft failures ( 3.0 % ) . Conclusion The contralateral normal knee anterior cruciate ligament is at a similar risk of anterior cruciate ligament tear ( 3.0 % ) as the anterior cruciate ligament graft after primary anterior cruciate ligament reconstruction ( 3.0 % ) Background : There is a lack of prospect i ve studies comparing the long-term outcome of endoscopic anterior cruciate ligament ( ACL ) reconstruction with either a patellar tendon or hamstring tendon autograft . Purpose : This prospect i ve longitudinal study compared the results of isolated endoscopic ACL reconstruction utilizing a 4-str and hamstring tendon ( HT ) or patellar tendon ( PT ) autograft over a 15-year period with respect to reinjury , clinical outcomes , and the development of osteoarthritis . Study Design : Cohort study ; Level of evidence , 2 . Methods : Ninety consecutive patients with isolated ACL rupture were reconstructed with a PT autograft , and 90 patients received an HT autograft , with an identical surgical technique . Patients were assessed at 2 , 5 , 7 , 10 , and 15 years . Assessment included the International Knee Documentation Committee ( IKDC ) knee ligament evaluation including radiographic evaluation , KT-1000 arthrometer testing , and Lysholm knee score . Results : Patients who received the PT graft had significantly worse outcomes compared with those who received the HT graft at 15 years for the variables of radiologically detectable osteoarthritis ( grade A : 46 % in PT and 69 % in HT ; P = .04 ) , motion loss ( extension deficit < 3 ° : 79 % in PT and 94 % in HT ; P = .03 ) , single-legged hop test ( grade A : 65 % in PT and 92 % in HT ; P = .001 ) , participation in strenuous activity ( very strenuous or strenuous : 62 % of PT and 77 % of HT ; P = .04 ) , and kneeling pain ( moderate or greater pain : 42 % of PT and 26 % of HT ; P = .04 ) . There was no significant difference between the HT and PT groups in overall IKDC grade ( grade A : 47 % of PT and 57 % of HT ; P = .35 ) . An ACL graft rupture occurred in 17 % of the HT group and 8 % of the PT group ( P = .07 ) . An ACL graft rupture was associated with nonideal tunnel position ( odds ratio [ OR ] , 5.0 ) and male sex ( OR , 3.2 ) . Contralateral ACL rupture occurred in significantly more PT patients ( 26 % ) than HT patients ( 12 % ) ( P = .02 ) and was associated with age ≤18 years ( OR , 4.1 ) and the PT graft ( OR , 2.6 ) . Conclusion : Anterior cruciate ligament reconstruction using ipsilateral autograft continues to show excellent results in terms of patient satisfaction , symptoms , function , activity level , and stability . The use of HT autograft does , however , show better outcomes than the PT autograft in all of these outcome measures . Additionally , at 15 years , the HT graft – reconstructed ACLs have shown a lower rate of radiological osteoarthritis Background : There is recent evidence that use of allograft tendons for anterior cruciate ligament ( ACL ) reconstruction in young patients may result in increased failure rates compared with autologous grafts . Hypothesis : Allograft ACL reconstruction will result in higher failure rates in young athletes compared with autograft reconstruction . Study Design : Cohort study ; Level of evidence , 2 . Methods : A prospect i ve cohort study of cadets at the United States Military Academy ( USMA ) was performed to assess performance of ACL reconstructions performed before entrance to service . Members of the classes of 2007 through 2013 who had undergone prior ACL reconstruction were identified through the Department of Defense Medical Evaluation Review Board reporting and waiver process and evaluated on the first day of matriculation . These participants were followed during their tenure at the academy with revision ACL reconstruction as the primary outcome measure of interest . Kaplan-Meier survival analysis was performed for all graft types using STATA with significance set as P < .05 . Results : A total of 120 cadets underwent 122 ACL reconstructions ( 2 bilateral ) before matriculation and compose the prospect i ve cohort . This cohort included 30 female and 90 male cadets . Of these 122 knees with prior ACL reconstructions , the grafts used were 61 bone – patellar tendon – bone ( BTB ) , 45 hamstring , and 16 allograft . A total of 20 failures occurred among this cohort at an average of 545 days from matriculation . Of the failures requiring revision , 7 were BTB ( 11 % of all BTB ) , 7 were allograft ( 44 % of all allograft ) , and 6 were hamstring ( 13 % of all hamstring ) . There was no significant difference in the graft failure between the BTB and hamstring autograft groups . In contrast , those who entered the USMA with an allograft were 7.7 times more likely to experience a subsequent graft failure during the follow-up period when compared with the BTB autograft group ( hazard ratio = 7.74 ; 95 % confidence interval [ CI ] , 2.67 - 22.38 ; P < .001 ) . When allografts were compared with all autografts combined , a similar increase failure was noted in the allograft group ( hazard ratio = 6.71 ; 95 % CI , 2.64 - 17.06 ; P < .001 ) . Conclusion : In this young active cohort , individuals having undergone an allograft ACL reconstruction were significantly more likely to experience clinical failure requiring revision reconstruction compared with those who underwent autologous graft reconstruction . The authors recommend the use of autograft in ACL reconstruction in young athletes Background : The aim of this prospect i ve r and omized study was to compare the outcomes of the anatomic double-bundle ( DB ) and anatomic single-bundle ( SB ) techniques 5 years after anterior cruciate ligament ( ACL ) reconstruction . Since more effective restoration of rotational laxity is considered the main advantage of the DB technique , the pivot-shift test was the primary outcome variable of the study . Hypothesis : Double-bundle ACL reconstruction will result in a better outcome in terms of the pivot-shift test . Study Design : R and omized controlled trial ; Level of evidence , 1 . Method Output:	In 2017 , it is not clear if an anterolateral ligament reconstruction is needed in the setting of primary anterior cruciate ligament reconstruction

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